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Title:
SUBSTITUTED PYRIDINES AS INHIBITORS OF DNMT1
Document Type and Number:
WIPO Patent Application WO/2017/216726
Kind Code:
A1
Abstract:
The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): (Iar) wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

Inventors:
ADAMS NICHOLAS DAVID (US)
BENOWITZ ANDREW B (US)
RUEDA BENEDE MARIA LOURDES (US)
EVANS KAREN ANDERSON (US)
FOSBENNER DAVID T (US)
KING BRYAN WAYNE (US)
LI MEI (US)
MILLER WILLIAM HENRY (US)
REIF ALEXANDER JOSEPH (US)
ROMERIL STUART PAUL (US)
SCHMIDT STANLEY J (US)
WIGGALL KENNETH (US)
Application Number:
PCT/IB2017/053509
Publication Date:
December 21, 2017
Filing Date:
June 13, 2017
Export Citation:
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Assignee:
GLAXOSMITHKLINE IP DEV LTD (GB)
International Classes:
C07D401/14; A61K31/44; A61P37/00; C07D401/04; C07D401/12; C07D413/14
Domestic Patent References:
WO2003008384A12003-01-30
WO2006078752A22006-07-27
Foreign References:
DE10238113A12003-06-18
US20080132525A12008-06-05
CA2030875A11992-05-27
Other References:
WIEBKE BRANDT ET AL: "Inhibitors of the RET tyrosine kinase based on a 2-(alkylsulfanyl)-4-(3-thienyl)nicotinonitrile scaffold", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, EDITIONS SCIENTIFIQUE ELSEVIER, PARIS, FR, vol. 45, no. 7, 12 March 2010 (2010-03-12), pages 2919 - 2927, XP028302983, ISSN: 0223-5234, [retrieved on 20100319], DOI: 10.1016/J.EJMECH.2010.03.017
GAO Z-G ET AL: "Emerging adenosine receptor agonists-an update", EXPERT OPINION ON EMERGING DRUGS, vol. 16, no. 4, 7 December 2011 (2011-12-07), pages 597 - 602, XP002773811
TING ET AL., GENES DEV., vol. 20, 2006, pages 3215 - 3231
ZHOU ET AL., ONCOL. LETT., vol. 5, 2014, pages 2130 - 2134
POP R; SHEARSTONE JR; SHEN Q; LIU Y; HALLSTROM K; KOULNIS M ET AL., A KEY COMMITMENT STEP IN ERYTHROPOIESIS IS SYNCHRONIZED WITH THE CELL CYCLE CLOCK THROUGH MUTUAL INHIBITION BETWEEN PU.1 AND S-PHASE PROGRESSION, 2010, pages 8
SHEARSTONE JR; POP R; BOCK C; BOYLE P; MEISSNER A; SOCOLOVSKY M., GLOBAL DNA DEMETHYLATION DURING MOUSE ERYTHROPOIESIS IN VIVO, vol. 334, 2011, pages 799 - 802
MABAERA R; RICHARDSON CA; JOHNSON K; HSU M; FIERING S; LOWREY CH, DEVELOPMENTAL- AND DIFFERENTIATION-SPECIFIC PATTERNS OF HUMAN +:- AND +:-GLOBIN PROMOTER DNA METHYLATION, vol. 110, 2007, pages 1343 - 52
CHIN J; SINGH M; BANZON V; VAITKUS K; IBANEZ V; KOUZNETSOVA T ET AL., TRANSCRIPTIONAL ACTIVATION OF THE +:-GLOBIN GENE IN BABOONS TREATED WITH DECITABINE AND IN CULTURED ERYTHROID PROGENITOR CELLS INVOLVES DIFFERENT MECHANISMS, vol. 37, 2009, pages 1131 - 42
AKPAN I; BANZON V; IBANEZ V; VAITKUS K; DESIMONE J; LAVELLE D., DECITABINE INCREASES FETAL HEMOGLOBIN IN PAPIO ANUBIS BY INCREASING +:-GLOBIN GENE TRANSCRIPTION, vol. 38, 2010, pages 989 - 93
DOVER GJ; CHARACHE SH; BOYER SH; TALBOT J; SMITH KD., 5-AZACYTIDINE INCREASES FETAL HEMOGLOBIN PRODUCTION IN A PATIENT WITH SICKLE CELL DISEASE, vol. 134, 1983, pages 475 - 88
SAUNTHARARAJAH Y; HILLERY CA; LAVELLE D; MOLOKIE R; DORN L; BRESSLER L ET AL., EFFECTS OF 5-AZA-2GÇ-DEOXYCYTIDINE ON FETAL HEMOGLOBIN LEVELS, RED CELL ADHESION, AND HEMATOPOIETIC DIFFERENTIATION IN PATIENTS WITH SICKLE CELL DISEASE, vol. 102, 2003, pages 3865 - 70
LEY TJ; DESIMONE J; NOGUCHI CT; TURNER PH; SCHECHTER AN; HELLER P ET AL., 5-AZACYTIDINE INCREASES +:-GLOBIN SYNTHESIS AND REDUCES THE PROPORTION OF DENSE CELLS IN PATIENTS WITH SICKLE CELL ANEMIA, vol. 62, 1983, pages 370 - 80
LOWREY CH; NIENHUIS AW., BRIEF REPORT: TREATMENT WITH AZACITIDINE OF PATIENTS WITH END-STAGE +:- THALASSEMIA, vol. 329, 1993, pages 845 - 8
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Claims:
What is claimed is: 1. A method of treating a disease selected from: cancer, pre-cancerous syndromes, beta haemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, in a mammal in need thereof, which comprises administering to such mammal a therapeutically effective amount of a compound of Formula (Icr):

wherein:

X1cr and X2cr are independently selected from: hydrogen,

cyano,

fluoro,

chloro,

bromo,

iodo,

C1-6alkyl,

Re,

-OC1-6alkyl,

-ORe,

cycloalkyl,

cycloalkyl substituted from 1 to 4 times by Rd,

heterocycle,

heterocycle substituted from 1 to 4 times by Rd,

-SH, and

-SRa; Ycr is selected from: S, NH, NRz, O, S(O) and S(O)2; R1cr is selected from: amino,

-NHRa, -NRbRc,

cyano,

fluoro,

chloro,

bromo,

iodo,

C1-6alkyl,

Re,

-OC1-6alkyl,

-ORe,

cycloalkyl,

cycloalkyl substituted from 1 to 4 times by Rd, heterocycle,

heterocycle substituted from 1 to 4 times by Rd, aryl,

aryl substituted from 1 to 4 times by Rd, heteroaryl,

heteroaryl substituted from 1 to 4 times by Rd, -SH, and

-SRa; R2cr is selected from: hydrogen,

C1-6alkyl, and

C1-6alkyl substituted with from 1 to 6 substituents independently selected from: halogen, -OH, -COOH; R3cr is selected from: aryl,

aryl substituted from 1 to 4 times by Rd, heteroaryl, and

heteroaryl substituted from 1 to 4 times by Rd;

R4cr is selected from: hydrogen,

C1-6alkyl, and

C1-6alkyl substituted with from 1 to 6 substituents independently selected from: halogen, -OH, -COOH;

R5cr is selected from: amino,

-NHRa,

-NRbRc,

aryl,

aryl substituted from 1 to 4 times by Rd,

-C1-6alkyl,

-OC1-6alkyl,

-ORe,

-Oaryl,

-Oaryl substituted from 1 to 4 times by Rd,

-Oheteroaryl,

-Oheteroaryl substituted from 1 to 4 times by Rd, -SH, and

-SRa; where: each Ra is independently selected from

C1-6alkyl,

Re,

aryl,

aryl substituted from 1 to 4 times by Rd, heteroaryl,

heteroaryl substituted from 1 to 4 times by Rd cycloalkyl,

cycloalkyl substituted from 1 to 4 times by Rd, heterocycloalkyl, and

heterocycloalkyl substituted from 1 to 4 times by Rd; Rb and Rc are independently selected from: C1-6alkyl,

Re,

aryl,

aryl substituted from 1 to 4 times by Rd,

heteroaryl,

heteroaryl substituted from 1 to 4 times by Rd;

cycloalkyl,

cycloalkyl substituted from 1 to 4 times by Rd,

heterocycloalkyl, and

heterocycloalkyl substituted from 1 to 4 times by Rd, or

Rb and Rc are taken together with the nitrogen to which they are

attached, and optionally from 1 to 3 additional heteroatoms independently selected from O, N, and S, to form

a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C1-6alkyl,

Re,

-ORe,

aryl,

aryl substituted from 1 to 4 times by Rd,

heteroaryl,

heteroaryl substituted from 1 to 4 times by Rd, cycloalkyl,

cycloalkyl substituted from 1 to 4 times by Rd, heterocycloalkyl, and

heterocycloalkyl substituted from 1 to 4 times by Rd, C1-4alkoxy,

–CN,

oxo,

-OH, -COOH,

-NO2,

-NH2,

-N(H)C1-5alkyl,

-N(H)Re, -N(C1-5alkyl)2,

-NReRe, -N(Re)C1-5alkyl, -ONHC(NH)NH2, -Oheterocycloalkyl, -NHcycloalkyl,

-N(C1-5alkyl)cycloalkyl, -NHheterocycloalkyl, -N(C1-5alkyl)heterocycloalkyl, -S(O)2C1-4alkyl, -SO2NH2

-S(O)2phenyl,

benzoyl,

2-methylcyclopropyl, imidazolyl,

(methoxypyridinylmethyl)amino, (methylcyclopropylmethyl)amino, (fluorophenylmethyl)amino, (methyloxetanylmethyl)amino, and (methylcyclobutylmethyl)amino; each Rd is independently selected from: fluoro,

chloro, bromo,

iodo,

C1-6alkyl,

Re,

heteroaryl,

heteroaryl substituted from 1 to 4 times by Rx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from:

fluoro, oxo, -OH, -COOH, -NH2, and–CN,

cycloalkyl,

cycloalkyl substituted from 1 to 4 times by Rx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from:

fluoro, oxo, -OH, -COOH, -NH2, and–CN,

heterocycloalkyl,

heterocycloalkyl substituted from 1 to 4 times by Rx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, fluoro, oxo, C1-6alkyl, and C1-6alkyl substituted

with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

aryl,

aryl substituted from 1 to 4 times by Rx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from:

fluoro, oxo, -OH, -COOH, -NH2, and–CN,

C1-4alkoxy,

C1-4alkoxy substituted with from 1 to 4 substituents independently selected

from: fluoro, oxo, -OH, -COOH, -NH2, -NHC1-4alkyl, -N(C1-4alkyl)2 and–CN,

-Oaryl,

-Oaryl substituted from 1 to 4 times by Rx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

-ORe,

-C(O)H,

-C(O)Rzz,

-C(O)aryl,

-C(O)aryl substituted from 1 to 4 times by Rzz,

-C(O)heteroaryl,

-C(O)heteroaryl substituted from 1 to 4 times by Rzz, -OC(O)H,

-CO(O)Rzz,

-OC(O)aryl,

-CO(O)aryl substituted from 1 to 4 times by Rzz,

-OC(O)heteroaryl,

-OC(O)heteroaryl substituted from 1 to 4 times by Rzz, mercapto,

-SRx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

-S(O)H,

-S(O)Rx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

-S(O)2H,

-S(O)2Rx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

-OS(O)2Rx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

-S(O)2NH2,

-S(O)2NHRx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

-S(O)2NRx1Rx2,

where Rx1 and Rx2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

-NHS(O)2H,

-NHS(O)2Rx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

-NHC(O)H,

-NHC(O)Rx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

-C(O)NH2,

-C(O)NHRx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

-C(O)NRx1Rx2,

where Rx1 and Rx2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN, -C(O)OH,

-C(O)ORx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

oxo,

hydroxy,

amino,

-NHRx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN, C1-6alkoxy, and C1-6alkoxy substituted with from 1 to 6 substituents independently

selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN, -NRx1Rx2,

where Rx1 and Rx2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, -S(O)2C1-6alkyl, -S(O)2C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and

CN, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH,

-NH2, and–CN,

boronic acid,

nitro,

cyano,

-NHC(O)NH2,

-NHC(O)NHRx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

-NHC(O)NRx1Rx2,

where Rx1 and Rx2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

each Re is independently selected from:

C1-6alkyl substituted with from 1 to 9 substitutents independently selected from:

fluoro,

chloro,

bromo,

iodo,

-OC1-6alkyl,

-OC1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

-OC(O)C1-6alkyl,

-OC(O)C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and -CN,

-ONHC(NH)NH2,

-OP(O)(OH)2,

mercapto,

-SRx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

-S(O)H,

-S(O)Rx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

-S(O)2H,

-S(O)2Rx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

oxo,

hydroxy,

amino,

-NHRxx,

where Rxx is selected from aryl, heteroaryl, cycloalkyl, cycloalkyl substituted with C1-4alkoxy, C1-4alkoxy substituted with from 1 to 6 substituents independently selected from: fluoro, triazolyl, cyclopropyl,oxo, -ORxy, -COOH,–CN, and -NRxyRxz, where Rxy and Rxz are Independently selected from: hydrogen, aryl, C1-5alkyl heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -ORxy, -COOH,–CN, and -NRxyRxz, where Rxy and Rxz are Independently selected from: hydrogen, aryl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, triazolyl, cyclopropyl,oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro and–COOH,

-NRx1Rx2,

where Rx1 and Rx2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

guanidino,

-C(O)OH,

-C(O)ORx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN, -C(O)NH2,

-C(O)NHRx,

where Rx is selected from aryl, heteroaryl, -OH, C1-4alkoxy, cycloalkyl, cycloalkyl substituted with HO-(C1-4alkyl)-, heterocyloalkyl, heterocyloalkyl substituted with HO-(C1-4alkyl)-, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, heteroaryl, -NH2, and–-CN,

-C(O)NRx1Rx2,

where Rx1 and Rx2 are each independently selected from aryl, heteroaryl, cycloalkyl, cycloalkyl substituted with HO-(C1-4alkyl)-, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

or Rx1 and Rx2 taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms independently selected from O, N, and S, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from fluoro, oxo, -OH, HO- (C1-4alkyl)-, -COOH, -NH2, and–CN,

aryl,

aryl substituted from 1 to 4 times by Rx,

where Rx is selected from fluoro, chloro, bromo, iodo, aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, -N(CH3)2, -NHC(O)C1-4alkyl, and– CN,

-Oaryl,

-Oaryl substituted from 1 to 4 times by Rx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN, heteroaryl,

heteroaryl substituted from 1 to 4 times by Rx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-4alkoxy, C1-6alkyl, and

C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

-Oheteroaryl,

-Oheteroaryl substituted from 1 to 4 times by Rx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

cycloalkyl,

cycloalkyl substituted from 1 to 4 times by Rx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

heterocycloalkyl,

heterocycloalkyl substituted from 1 to 4 times by Rx,

where Rx is selected from oxo, -OH,

-N(C1-4alkyl)2, aryl, heteroaryl,

cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, -N(CH3)2, and -CN,

-S(O)2NH2,

-S(O)2NHRx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

-S(O)2NRx1Rx2,

- where Rx1 and Rx2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

-NHS(O)2H,

-NHS(O)2Rx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

-OC(O)NH2,

-NHC(O)Rx,

where Rx is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and -CN

-NHC(O)NHRxp,

where Rxp is selected from heteroaryl, cycloalkyl, heterocyloalkyl, and C1-6alkyl substituted with from 1 to 4 substituents independently selected from: -COOH, -NH2, and –CN,

-NHC(O)NRx3Rx4,

where Rx3 and Rx4 are each independently selected from heteroaryl, cycloalkyl, heterocyloalkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from:

-COOH, -NH2, and–CN,

-NHC(O)C(O)NH2,

-NO2, and

-CN; and Rz is selected from

C1-6alkyl, Re,

cycloalkyl,

cycloalkyl substituted from 1 to 4 times by Rd, heterocycloalkyl, and

heterocycloalkyl substituted from 1 to 4 times by Rd; and Rzz is selected from

C1-6alkyl, and

Re; provided that:

X1cr and X2cr are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

2. A method according to claim 1 wherein the compound is a compound of Formula (IVccr):

wherein:

X41ccr and X42ccr are independently selected from: -CN, methyl, fluoro, chloro, bromo and

iodo;

Y4ccr is selected from: S and NH; R41ccr is selected from: C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, bromo, iodo, oxo, C1-4alkyloxy, -OH, -COOH, -NH2

-N(H)C1-4alkyl, -N(C1-4alkyl)2 and–CN,

C1-4alkyloxy,

C1-4alkyloxy substituted from 1 to 4 times by fluoro,

-N(H)C1-4alkyl, -N(C1-4alkyl)2,

-SC1-4alkyl,

aryl,

aryl substituted with from 1 to 4 substituents

independently selected from:

fluoro,

chloro,

bromo,

iodo,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH2 and–CN,

C1-4alkoxy,

–CN,

oxo,

-OH,

-NO2, and

-NH2,

heteroaryl,

heteroaryl substituted with from 1 to 4 substituents

independently selected from:

fluoro, chloro,

bromo,

iodo,

C1-6alkyl, C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH2 and–CN,

C1-4alkoxy,

–CN,

oxo,

-OH,

-NO2, and

-NH2,

cycloalkyl,

cycloalkyl substituted with from 1 to 4 substituents

independently selected from:

fluoro,

chloro,

bromo,

iodo,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH2 and–CN,

C1-4alkoxy,

–CN,

oxo,

-OH,

-NO2, and

-NH2; R43ccr is selected from:

aryl,

aryl substituted with from 1 to 4 substituents independently selected

from:

fluoro,

chloro,

bromo,

iodo,

C1-4alkoxy,

C1-4alkoxy substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, oxo, -OH, -NH2, -NHCH3, and–N(CH3)2,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -S(O)2C1-4alkyl, -CN, -OR49 and – NR46R47,

where R46 and R47 are independently selected from: hydrogen, -S(O)2CH3, pyrazole,

C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR48R49, where R48 and R49 are independently selected from: hydrogen, phenyl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo,

-OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro and–COOH, –CN,

oxo,

-OH,

heterocycloalkyl,

heterocycloalkyl independently substituted once or twice with a

substituent selected from: fluoro and oxo,

-N(CH3)S(O)2CFH2,

-N(CH3)S(O)2CF2H,

-N(CH3)S(O)2CF3,

-OS(O)2CH3,

-S(O)2NH2,

-S(O)2NHCH3,

–NR80a’R81a’ where R80a’ and R81a’ are independently selected form: hydrogen, -S(O)2CH3, phenyl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituentsindependently selected from: fluoro, oxo, -OH, -NH2, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro and–COOH,

boronic acid,

-NO2, and

-NH2,

heteroaryl, and

heteroaryl substituted with from 1 to 4 substituents independently selected from: fluoro,

chloro,

bromo,

iodo,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -CN, -OR49 and–NR46R47,

where R46 and R47 are independently selected from: hydrogen, -S(O)2CH3, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR48R49, where R48 and R49 are independently selected from: hydrogen, phenyl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro and–COOH, C1-4alkoxy,

–CN,

oxo,

-OH,

-S(O)2NH2,

-S(O)2NHCH3,

-NO2, and

-NH2; and R44ccr and R45ccr are independently selected from:

hydrogen, C1-6alkyl, C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: phenyl, morpholino, triazolyl, imidazolyl, pyrrolidinyl, -OC(O)NH2, -OCH2CH2NH2,

-ONHC(NH2)NH2, -NHCH2C(CH3)3, -NOCH3, -NHOH,

-NHCH2CH2F, -N(CH3)CH2CH2OCH3, -N(CH2CH3)2, -NCH(CH2OH)2, -N(CH2CH2OH)2, -NHCH2CH2OH,

-NHCH2CH2NH2, -N(CH3)C(CH3)2CH2OH, -NHCH2CH3, -NHCH2CH2OCH3, -N(CH3)CH2CH2OH, -NHC(O)C(O)NH2, -N(CH3)CH2CH2CH2OH, -N(CH3)CH2CH(OH)CH2OH,

-N(CH3)CH2CH2NH2, oxo, -NHCH2C(CH3)2CH2OH, -OH, -NH2, -NHCH3, -NHCH2CH2CH2OH, -N(CH3)2, -N(CH3)CH2CH3, -NHOC(CH3)2NH2, -N(CH3)CH2cyclopropyl, -NHCH2cyclopropyl, -NHoxetanyl, -NCH2CH2triazole, piperazinyl, piperidinyl, pyrazolyl, azepinyl, azetidinyl, methoxy, and cyclopropylamino,

where said phenyl, morpholino, triazolyl, imidazolyl, azepinyl, azetidinyl, pyrrolidinyl piperazinyl, piperidinyl, oxetanyl, cyclopropyl, and pyrazolyl are optionally substituted with from 1 to 4 substituents independently selected from: methyl, fluoro, -NH2, -N(CH3)2, hydroxymethyl, oxo, -OH, and–CH2NH2, cycloalkyl,

cycloalkyl substituted with from one to five substituents

independently selected from:

fluoro, chloro,

-OH,

C1-6alkyl, and

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro;

heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C1-6alkyl, C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH2 and–CN, aryl,

C1-4alkoxy,

C1-4alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

–CN,

oxo,

-OH,

-COOH,

-NO2,

-NH2, and

SO2NH2, or

R44ccr and R45ccr are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms independently selected from O, N, and S, to form a heterocycloalkyl, which is optionally

substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, C1-4alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl-, -OH, -NH2, -N(H)C1-5alkyl, aminoheterocycloalkyl-, -N(C1-5alkyl)2, --CN, -N(C1-4alkyl)(CH2OCH3), and -NHC1-4alkyl substituted by one or two substituents independently selected from oxo, NH2, and -OH,

aryl,

cycloalkyl,

heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents independently selected from: C1-6alkyl, -C1-6alkylOH, fluoro, -C1-6alkylNH2, chloro, bromo, iodo, oxo, -OH, -NH2 and–CN, C1-4alkoxy,

C1-4alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN, –CN,

oxo,

-OH,

-OP(O)(OH)2,

-COOH,

-NO2,

-NH2,

-N(H)C1-5alkyl,

-N(H)C1-6alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, bromo, iodo, C1-4alkoxy, oxo, phenyl, cycloalkyl, aminoC1-4alkoxy, heterocycloalkyl,

methylheterocycloalkyl, -OH, -NH2, -N(H)C1-4alkyl, -N(C1-4alkyl)2, and–CN,

-Ooxetanyl,

-ONHC(NH)NH2,

-NHcyclopropyl,

-NHoxetanyl,

-N(C1-5alkyl)2,

-S(O)2CH2CH3,

S(O)2CH2CH2CH3,

-S(O)2CH3,

-SO2NH2,

-S(O)2phenyl,

benzoyl,

benzylamino,

-propylpyrrolidinyl,

-methylcyclopropyl, cyclobutylamino,

cyclobutyl-N(CH3)-,

piperidinyl,

imidazolyl, morpholinyl,

morpholinylmethyl,

methylpiperazinylmethyl, methylpiperazinyl,

pyrrolidinyl,

pyrrolidinylmethyl,

(methoxypyridinylmethyl)amino, methylpyrrolidinyl,

difluoropyrrolidinyl,

dimethylpyrrolidinyl,

(methylcyclopropylmethyl)amino, hydroxymethylpyrrolidinyl, fluoropyrrolidinyl,

fluorophenylmethylamino, piperazinlymethyl,

oxazolidinyl,

(methyloxetanmethyl)amino, (methylcyclobutylmethyl)amino, oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl;

provided that:

R44ccr and R45ccr are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

3. The method of claim 2 wherein the mammal is a human.

4. A method of inhibiting DNMT1 activity in a mammal in need thereof, which comprises administering to such mammal a therapeutically effective amount of a compound of Formula (IVccr), as described in claim 2 or a pharmaceutically acceptable salt thereof.

5. The method of claim 4 wherein the mammal is a human.

6. The method of claim 1 wherein the compound is selected from:

N-(4-((3,5-Dicyano-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1-yl)pyridin-2- ylthio)methyl)benzyl)acetamide;

2-(4-(Aminomethyl)benzylthio)-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1-yl)pyridine- 3,5-dicarbonitrile;

tert-Butyl 4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzylcarbamate;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzamide;

2-((4-(Aminomethyl)benzyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridine- 3,5-dicarbonitrile;

2-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)acetic acid;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzoic acid;

2-(Dimethylamino)-4-ethyl-6-(((6-oxo-1,6-dihydropyridin-3-yl)methyl)thio)pyridine- 3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)thiazol-2-yl)acetamide;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzenesulfonamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl) acetamide; tert-Butyl (2-((4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)amino)-2-oxoethyl)carbamate;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)methanesulfonamide;

2-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)acetamide;

2-(4-Aminopiperidin-1-yl)-6-(benzylthio)-4-ethylpyridine-3, 5-dicarbonitrile;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl acetate;

2-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl acetamide;

2-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylacetamide;

4-Ethyl-2-((4-(hydroxymethyl)benzyl)thio)-6-(4-methyl-1,4-diazepan-1-yl)pyridine- 3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)-2-hydroxyacetamide;

Example 87N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2-yl)thio) methyl)benzyl)propionamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)isobutyramide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)-3-methylbutanamide;

4-Ethyl-2-((4-(((2-hydroxyethyl)amino)methyl)benzyl)thio)-6-(4-methyl-1,4- diazepan-1-yl)pyridine-3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-6-(4-methyl-1,4-diazepan-1-yl)-4-(methylamino)pyridin-2- yl)thio)methyl)benzyl)acetamide;

2-(((2-Acetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)methyl)thio)-6-(dimethylamino)-4- ethylpyridine-3,5-dicarbonitrile; 2-((4-Cyanobenzyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridine-3,5- dicarbonitrile;

2-Amino-N-(1-(6-(benzylthio)-3,5-dicyano-4-ethylpyridin-2-yl)piperidin-4- yl)acetamide;

2-Amino-N-(1-(6-(benzylthio)-3,5-dicyano-4-ethylpyridin-2-yl)piperidin-4-yl)-2- methylpropanamide;

3-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)propanamide;

(S)-2-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)propanamide;

(R)-2-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)propanamide;

1-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)-3-ethylurea;

1-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)-3-phenylurea;

N-(4-(((3,5-Dicyano-6-(4-methyl-1,4-diazepan-1-yl)-4-(methylthio)pyridin-2- yl)thio)methyl)benzyl)acetamide;

(E)-3-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2- yl)thio)methyl)phenyl)acrylic acid;

N-(4-(((3,5-Dicyano-4-ethyl-6-((2-hydroxyethyl)(methyl)amino)pyridin-2- yl)thio)methyl)benzyl)acetamide;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2-yl)thio)methyl)-N- methylbenzenesulfonamide;

N-(4-(((3,5-Dicyano-4-ethoxy-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)acetamide;

N-(4-(((6-(4-Aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2- yl)thio)methyl)benzyl)acetamide;

(S)-2-((1-(6-((4-(Acetamidomethyl)benzyl)thio)-3,5-dicyano-4-ethylpyridin-2- yl)piperidin-4-yl)oxy)ethyl 2-amino-3-methylbutanoate; (S)-2-((6-((4-(Acetamidomethyl)benzyl)thio)-3,5-dicyano-4-ethylpyridin-2- yl)(methyl)amino)ethyl 2-amino-3-methylbutanoate;

2-Amino-N-(4-(((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2- yl)thio)methyl)benzyl)acetamide;

4-Ethyl-2-(4-methyl-1,4-diazepan-1-yl)-6-((4-((2-oxopyrrolidin-1- yl)methyl)benzyl)thio)pyridine-3,5-dicarbonitrile;

2-((4-(Aminomethyl) benzyl)thio)-6-(dimethylamino)-4-ethylpyridine-3,5- dicarbonitrile;

N-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl) thio) methyl) phenyl) acetamide;

N-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)methyl)benzyl)-2- hydroxyacetamide;

3-Amino-N-(4-(((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2- yl)thio)methyl)benzyl)propanamide;

(S)-1-(6-((4-(Acetamidomethyl)benzyl)thio)-3,5-dicyano-4-ethylpyridin-2- yl)azetidin-3-yl 2-amino-3-methylbutanoate;

N-(4-(((3,5-Dicyano-4-ethyl-6-methylpyridin-2-yl)thio)methyl)benzyl)acetamide; 2-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)methyl)-1H-pyrazol- 1-yl)acetamide;

N-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)methyl)phenyl) methanesulfonamide;

(S)-1-(6-((4-(Acetamidomethyl)benzyl)thio)-3,5-dicyano-4-ethylpyridin-2- yl)piperidin-4-yl 2-amino-3-methylbutanoate;

N-(1-(6-((4-(Acetamidomethyl)benzyl)thio)-3,5-dicyano-4-ethylpyridin-2- yl)piperidin-4-yl)acetamide;

2-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)methyl)phenyl)-N-(2- hydroxyethyl)acetamide;

4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)methyl)-N-(2- hydroxyethyl)benzamide; 2-((4-(1H-Imidazol-1-yl)benzyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridine- 3,5-dicarbonitrile;

2-((4-Cyano-3-methylbenzyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridine- 3,5-dicarbonitrile;

tert-Butyl (4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)carbamate;

2-((4-Aminobenzyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridine-3,5- dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)acetamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl) methanesulfonamide;

2-(((6-Aminopyridin-3-yl)methyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1- yl)pyridine-3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)-2-hydroxyacetamide;

2-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)acetamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(3-oxopiperazin-1-yl)pyridin-2-yl)thio) methyl) benzyl) acetamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(3-hydroxypyrrolidin-1-yl)pyridin-2- yl)thio)methyl)benzyl)acetamide;

N-(4-(1-(3,5-Dicyano-6-(4-(dimethylamino)piperidin-1-yl)-4-ethylpyridin-2- ylthio)propyl)benzyl)acetamide;

N-(5-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)pyridin-2-yl)methanesulfonamide;

2-(6-(4-(Acetamidomethyl)benzylthio)-3,5-dicyano-4-ethylpyridin-2-ylthio)-2- phenylacetamide;

4-Ethyl-2-((4-(pyridin-3-yl)benzyl)thio)-6-(4-(pyrrolidin-1-yl)piperidin-1-yl)pyridine- 3,5-dicarbonitrile; 4-Ethyl-2-((4-(pyridin-4-yl)benzyl)thio)-6-(4-(pyrrolidin-1-yl)piperidin-1-yl)pyridine- 3,5-dicarbonitrile;

2-Amino-N-(1-(3,5-dicyano-4-ethyl-6-((4-sulfamoylbenzyl)thio)pyridin-2- yl)piperidin-4-yl)acetamide;

2-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-(2-hydroxyethyl)acetamide;

2-(((1H-Indol-5-yl)methyl)thio)-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1-yl)pyridine- 3,5-dicarbonitrile;

4-(((6-(4-Aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-yl)thio)methyl) benzenesulfonamide;

2-((Benzo[d][1,3]dioxol-5-ylmethyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1- yl)pyridine-3,5-dicarbonitrile;

2-(((3,3-Dimethoxy-2-oxoindolin-5-yl)methyl)thio)-4-ethyl-6-(4-methyl-1,4- diazepan-1-yl)pyridine-3,5-dicarbonitrile;

2-(((2,3-Dioxoindolin-5-yl)methyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1- yl)pyridine-3,5-dicarbonitrile;

N-(4-(((6-(((4H-1,2,4-Triazol-3-yl)methyl)(methyl)amino)-3,5-dicyano-4- ethylpyridin-2-yl)thio)methyl)benzyl)acetamide;

4-Ethyl-2-((4-(pyridin-2-yl)benzyl)thio)-6-(4-(pyrrolidin-1-yl)piperidin-1-yl)pyridine- 3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylacetamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2-yl) thio)methyl)phenyl)-N-methylmethanesulfonamide;

4-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- ylthio)methyl)phenylboronic acid;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)-2-(methylamino)acetamide;

2-((4-Amino-3-fluorobenzyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridine- 3,5-dicarbonitrile; N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2-yl)thio)methyl)- 2-fluorophenyl)methanesulfonamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2-yl) thio)methyl)-2-fluorophenyl)acetamide;

2-(4-Aminopiperidin-1-yl)-4-ethyl-6-(((1-(2-hydroxyethyl)-1H-pyrazol-4- yl)methyl)thio)pyridine-3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(3-hydroxypyrrolidin-1-yl)pyridin-2- yl)thio)methyl)benzyl)-2-hydroxyacetamide;

N-(4-(((6-((2-Amino-2-oxoethyl) (methyl) amino)-3, 5-dicyano-4-ethylpyridin-2-yl) thio) methyl) benzyl)-2-hydroxyacetamide;

2-(4-(2-(Dimethylamino)ethoxy)benzylthio)-4-ethyl-6-(4-methyl-1,4-diazepan-1- yl)pyridine-3,5-dicarbonitrile;

4-Ethyl-2-(4-methyl-1,4-diazepan-1-yl)-6-((4-(methylsulfonyl)benzyl)thio)pyridine- 3,5-dicarbonitrile;

2-(4-Aminopiperidin-1-yl)-6-(((1-(2,3-dihydroxypropyl)-1H-pyrazol-4-yl)methyl)thio)- 4-ethylpyridine-3,5-dicarbonitrile;

4-Ethyl-2-(4-methyl-1,4-diazepan-1-yl)-6-((4-(4-methylpiperazin-1- yl)benzyl)thio)pyridine-3,5-dicarbonitrile;

4-Ethyl-2-(4-methyl-1,4-diazepan-1-yl)-6-((4-(((2-oxopyrrolidin-3- yl)amino)methyl)benzyl)thio)pyridine-3,5-dicarbonitrile;

2-(((1H-Benzo[d]imidazol-5-yl)methyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1- yl)pyridine-3,5-dicarbonitrile;

4-Ethyl-2-(4-methyl-1,4-diazepan-1-yl)-6-(4- (methylsulfonylmethyl)benzylthio)pyridine-3,5-dicarbonitrile;

2-{[3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl]sulfanyl}-2-phenylacetamide; N-(4-(((3,5-dicyano-4-ethyl-6-(methyl(2-(neopentylamino)ethyl)amino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-((2-((2- methoxyethyl)(methyl)amino)ethyl)(methyl)amino)pyridin-2-yl)thio)methyl)phenyl)-N- methylmethanesulfonamide; N-(4-(((3,5-dicyano-4-ethyl-6-(methyl(2-(methylamino)ethyl)amino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-((2-((2- methoxyethyl)amino)ethyl)(methyl)amino)pyridin-2-yl)thio)methyl)phenyl)-N- methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(methyl(2-((1- methylcyclopropyl)amino)ethyl)amino)pyridin-2-yl)thio)methyl)phenyl)-N- methylmethanesulfonamide;

N-(4-(((3,5-dicyano-6-((2-(dimethylamino)ethyl)(methyl)amino)-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((6-((2-aminoethyl)(methyl)amino)-3,5-dicyano-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

2-(4-aminopiperidin-1-yl)-4-ethyl-6-((4- ((methylsulfonyl)methyl)benzyl)thio)pyridine-3,5-dicarbonitrile;

N-(4-(((3,5-dicyano-4-ethyl-6-((2-((2-fluoroethyl)amino)ethyl)(methyl)amino)pyridin- 2-yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

2-amino-N-(4-(((3,5-dicyano-6-((2-(diethylamino)ethyl)(methyl)amino)-4- ethylpyridin-2-yl)thio)methyl)benzyl)acetamide;

4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2-yl)thio)methyl)-N- (1H-pyrazol-4-yl)benzamide;

rel-2-amino-N-(4-(((6-(cis-4-amino-3-fluoropiperidin-1-yl)-3,5-dicyano-4- ethylpyridin-2-yl)thio)methyl)benzyl)acetamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-(isopropylamino)piperidin-1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-((2-methoxyethyl)amino)piperidin-1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-(neopentylamino)piperidin-1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(methyl(2-(pyrrolidin-1-yl)ethyl)amino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide; N-(4-(((3,5-dicyano-6-(2-((dimethylamino)methyl)morpholino)-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

2-amino-N-(1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)piperidin-4-yl)-2-methylpropanamide;

N-(4-(((3,5-dicyano-6-(4-(cyclopropylamino)piperidin-1-yl)-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(2-(pyrrolidin-1-ylmethyl)morpholino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(methyl(2-(piperidin-1-yl)ethyl)amino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-6-((2-(diethylamino)ethyl)(methyl)amino)-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-6-(2-((diethylamino)methyl)morpholino)-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

(R)-2-amino-N-(1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)piperidin-4-yl)propanamide;

(S)-2-amino-N-(1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)piperidin-4-yl)propanamide;

N-(4-(((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

2-amino-N-(1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)piperidin-4-yl)acetamide;

N-(4-(((6-(2-(aminomethyl)morpholino)-3,5-dicyano-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)-1-fluoro-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(2-((methylamino)methyl)morpholino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide; N-(4-(((3,5-dicyano-6-(3-((dimethylamino)methyl)piperidin-1-yl)-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

2-(4-aminopiperidin-1-yl)-6-((4-(1,1-dioxidoisothiazolidin-2-yl)benzyl)thio)-4- ethylpyridine-3,5-dicarbonitrile;

2-(4-aminopiperidin-1-yl)-6-((4-(1,1-dioxido-1,2-thiazinan-2-yl)benzyl)thio)-4- ethylpyridine-3,5-dicarbonitrile;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)-1,1-difluoro-N-methylmethanesulfonamide;

2-((4-(1,1-dioxidoisothiazolidin-2-yl)benzyl)thio)-4-ethyl-6-(4- (neopentylamino)piperidin-1-yl)pyridine-3,5-dicarbonitrile;

2-((4-(1,1-dioxido-1,2-thiazinan-2-yl)benzyl)thio)-4-ethyl-6-(4- (neopentylamino)piperidin-1-yl)pyridine-3,5-dicarbonitrile;

4-(((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-yl)thio)methyl)phenyl methanesulfonate;

(R)-2-amino-N-((1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)pyrrolidin-3-yl)methyl)acetamide;

(S)-2-amino-N-((1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)pyrrolidin-3-yl)methyl)acetamide;

N-(4-(1-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2- yl)thio)ethyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-methoxypyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide; and

N-(4-(((3,5-dicyano-4-ethyl-6-(4-((2-hydroxyethyl)amino)piperidin-1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide; or a pharmaceutically acceptable salt or prodrug thereof.

7. A compound according to Formula (IVccr): wherein: X41ccr and X42ccr are independently selected from: -CN, methyl, fluoro, chloro, bromo and

iodo;

Y4ccr is selected from: S and NH; R41ccr is selected from: C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo,

iodo, oxo, C1-4alkyloxy, -OH, -COOH, -NH2 -N(H)C1-4alkyl, -N(C1-4alkyl)2 and–CN,

C1-4alkyloxy,

C1-4alkyloxy substituted from 1 to 4 times by fluoro,

-N(H)C1-4alkyl,

-N(C1-4alkyl)2,

-SC1-4alkyl,

aryl,

aryl substituted with from 1 to 4 substituents

independently selected from:

fluoro,

chloro,

bromo,

iodo, C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH2 and–CN,

C1-4alkoxy,

–CN,

oxo,

-OH,

-NO2, and

-NH2,

heteroaryl,

heteroaryl substituted with from 1 to 4 substituents

independently selected from:

fluoro,

chloro,

bromo,

iodo,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH2 and–CN,

C1-4alkoxy,

–CN,

oxo,

-OH,

-NO2, and

-NH2,

cycloalkyl,

cycloalkyl substituted with from 1 to 4 substituents

independently selected from: fluoro,

chloro,

bromo,

iodo,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH2 and–CN,

C1-4alkoxy,

–CN,

oxo,

-OH,

-NO2, and

-NH2;

R43ccr is selected from:

aryl,

aryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C1-4alkoxy,

C1-4alkoxy substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, oxo, -OH, -NH2, -NHCH3, and–N(CH3)2, C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -S(O)2C1-4alkyl, -CN, -OR49 and – NR46R47,

where R46 and R47 are independently selected from: hydrogen, -S(O)2CH3, pyrazole,

C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR48R49, where R48 and R49 are independently selected from: hydrogen, phenyl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro and–COOH, –CN,

oxo,

-OH,

heterocycloalkyl,

heterocycloalkyl independently substituted once or twice with a

substituent selected from: fluoro and oxo,

-N(CH3)S(O)2CFH2,

-N(CH3)S(O)2CF2H,

-N(CH3)S(O)2CF3,

-OS(O)2CH3,

-S(O)2NH2,

-S(O)2NHCH3, –NR80aR81a where R80a and R81a are independently selected form: hydrogen, -S(O)2CH3, phenyl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituentsindependently selected from: fluoro, oxo, -OH, -NH2, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro and–COOH,

boronic acid,

-NO2, and

-NH2,

heteroaryl, and

heteroaryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -CN, -OR49 and–NR46R47,

where R46 and R47 are independently selected from: hydrogen, -S(O)2CH3, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR48R49, where R48 and R49 are independently selected from: hydrogen, phenyl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro and–COOH, C1-4alkoxy,

–CN,

oxo,

-OH,

-S(O)2NH2,

-S(O)2NHCH3,

-NO2, and

-NH2; and

R44ccr and R45ccr are independently selected from:

hydrogen, C1-6alkyl, C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: phenyl, morpholino, triazolyl, imidazolyl, pyrrolidinyl, -OC(O)NH2, -OCH2CH2NH2,

-ONHC(NH2)NH2, -NHCH2C(CH3)3, -NOCH3, -NHOH, -NHCH2CH2F, -N(CH3)CH2CH2OCH3, -N(CH2CH3)2, -NCH(CH2OH)2, -N(CH2CH2OH)2, -NHCH2CH2OH,

-NHCH2CH2NH2, -N(CH3)C(CH3)2CH2OH, -NHCH2CH3, -NHCH2CH2OCH3, -N(CH3)CH2CH2OH, -NHC(O)C(O)NH2, -N(CH3)CH2CH2CH2OH, -N(CH3)CH2CH(OH)CH2OH,

-N(CH3)CH2CH2NH2, oxo, -NHCH2C(CH3)2CH2OH, -OH, -NH2, -NHCH3, -NHCH2CH2CH2OH, -N(CH3)2, -N(CH3)CH2CH3, -NHOC(CH3)2NH2, -N(CH3)CH2cyclopropyl, -NHCH2cyclopropyl, -NHoxetanyl, -NCH2CH2triazole, piperazinyl, piperidinyl, pyrazolyl, azepinyl, azetidinyl, methoxy, and cyclopropylamino,

where said phenyl, morpholino, triazolyl, imidazolyl, azepinyl, azetidinyl, pyrrolidinyl piperazinyl, piperidinyl, oxetanyl, cyclopropyl, and pyrazolyl are optionally substituted with from 1 to 4 substituents independently selected from: methyl, fluoro, -NH2, -N(CH3)2, hydroxymethyl, oxo, -OH, and–CH2NH2, cycloalkyl,

cycloalkyl substituted with from one to five substituents

independently selected from:

fluoro,

chloro,

-OH,

C1-6alkyl, and

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro; heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH2 and–CN, aryl,

C1-4alkoxy,

C1-4alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

–CN,

oxo,

-OH,

-COOH,

-NO2,

-NH2, and

SO2NH2, or

R44ccr and R45ccr are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms independently selected from O, N, and S, to form a heterocycloalkyl, which is optionally

substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, C1-4alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl-, -OH, -NH2, -N(H)C1-5alkyl, aminoheterocycloalkyl-, -N(C1-5alkyl)2, --CN, -N(C1-4alkyl)(CH2OCH3), and -NHC1-4alkyl substituted by one or two substituents independently selected from oxo, NH2, and -OH,

aryl,

cycloalkyl,

heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents independently selected from: C1-6alkyl, -C1-6alkylOH, fluoro, -C1-6alkylNH2,

chloro, bromo, iodo, oxo, -OH, -NH2 and–CN, C1-4alkoxy, C1-4alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

–CN,

oxo,

-OH,

-OP(O)(OH)2,

-COOH,

-NO2,

-NH2,

-N(H)C1-5alkyl, -N(H)C1-6alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, bromo, iodo, C1-4alkoxy, oxo, phenyl, cycloalkyl, aminoC1-4alkoxy, heterocycloalkyl, methylheterocycloalkyl, -OH, -NH2, -N(H)C1-4alkyl, -N(C1-4alkyl)2, and–CN, -Ooxetanyl,

-ONHC(NH)NH2,

-NHcyclopropyl,

-NHoxetanyl,

-N(C1-5alkyl)2,

-S(O)2CH2CH3,

S(O)2CH2CH2CH3, -S(O)2CH3,

-SO2NH2,

-S(O)2phenyl,

benzoyl,

benzylamino,

-propylpyrrolidinyl,

-methylcyclopropyl, cyclobutylamino,

cyclobutyl-N(CH3)-, piperidinyl,

imidazolyl,

morpholinyl,

morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinyl,

pyrrolidinyl,

pyrrolidinylmethyl,

(methoxypyridinylmethyl)amino, methylpyrrolidinyl,

difluoropyrrolidinyl, dimethylpyrrolidinyl,

(methylcyclopropylmethyl)amino, hydroxymethylpyrrolidinyl, fluoropyrrolidinyl,

fluorophenylmethylamino, piperazinlymethyl,

oxazolidinyl,

(methyloxetanmethyl)amino,

(methylcyclobutylmethyl)amino, oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl;

provided that:

R44ccr and R45ccr are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

8. A compound according to Claim 7 represented by the following Formula (Vccr):

wherein: Y5ccr is selected from: S and NH; R50ccr is selected from: C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro, -N(H)C1-4alkyl,

-N(C1-4alkyl)2,

-SC1-4alkyl,

C1-4alkyloxy,

aryl,

aryl substituted with from one to five substituents independently selected from:

fluoro,

chloro,

-OH,

C1-6alkyl, and

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro, heteroaryl,

heteroaryl substituted with from one to five substituents

independently selected from:

fluoro,

chloro,

-OH,

C1-6alkyl, and

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro, cycloalkyl,

cycloalkyl substituted with from one to five substituents

independently selected from:

fluoro,

chloro,

-OH,

C1-6alkyl, and C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro; R52ccr is selected from:

aryl,

aryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro, C1-4alkoxy,

C1-4alkoxy substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, oxo, -OH, -NH2, -NHCH3, and–N(CH3)2,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -S(O)2CH3, -CN, -OR59 and–NR56R57, where R56 and R57 are independently selected from: hydrogen, -S(O)2CH3, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR58R59, where R58 and R59 are independently selected from: hydrogen, phenyl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro and–COOH, oxo,

-CN,

tetrahydroisothiazolyl,

tetrahydroisothiazolyl substituted twice by oxo, tetrahydro-1,2-thiazinyl,

tetrahydro-1,2-thiazinyl substituted twice by oxo, -N(CH3)S(O)2CH3, -N(CH3)S(O)2CFH2,

-N(CH3)S(O)2CF2H,

-N(CH3)S(O)2CF3,

-OS(O)2CH3,

-S(O)2NH2,

-S(O)2NHCH3,

–NR80a’R81a’ where R80a’ and R81a’ are independently selected form: hydrogen, -S(O)2CH3, phenyl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituentsindependently selected from: fluoro, oxo, -OH, -NH2, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6

times by fluoro and–COOH, and

-OH;

heteroaryl, and

heteroaryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -CN, -OR59 and–NR56R57,

where R56 and R57 are independently selected from: hydrogen, -S(O)2CH3, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl,

-OC1-5alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR58R59, where R58 and R59 are independently selected from: hydrogen, phenyl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro and–COOH, oxo,

-S(O)2NH2,

-S(O)2NHCH3,

-OH; and

R53ccr and R54ccr are independently selected from:

hydrogen,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: phenyl, morpholino, triazolyl, imidazolyl, -CH2CH2pyrrolidinyl, -OC(O)NH2, -OCH2CH2NH2, -ONHC(NH2)NH2, -NHCH2C(CH3)3, -NOCH3, -NHOH, -NHCH2CH2F, -N(CH3)CH2CH2OCH3, -N(CH2CH3)2, -NCH(CH2OH)2, -N(CH2CH2OH)2, -NHCH2CH2OH, -NHCH2CH2NH2, -N(CH3)CH2(CH3)2CH2OH, -NHCH2CH3, -NHCH2CH2OCH3, -N(CH3)CH2CH2OH, -NHC(O)C(O)NH2, -N(CH3)CH2CH2CH2OH, -N(CH3)CH2CH(OH)CH2OH, -N(CH3)CH2CH2NH2, oxo, -NHCH2C(CH3)2CH2OH, -OH, -NH2, -NHCH3, -NHCH2CH2CH2OH, -N(CH3)2, -N(CH3)CH2CH3, -NHOC(CH3)2NH2, -N(CH3)CH2cyclopropyl, -NHCH2cyclopropyl, -NHoxetanyl, -NCH2CH2triazole, piperazinyl, piperidinyl, pyrazolyl, azepinyl, azetidinyl, methoxy, and cyclopropylamino,

where said phenyl, morpholino, triazolyl, imidazolyl, azepinyl, azetidinyl, pyrrolidinyl piperazinyl, piperidinyl, oxetanyl, cyclopropyl, and pyrazolyl are optionally substituted with from 1 to 4 substituents independently selected from: methyl, fluoro, -NH2, -N(CH3)2, hydroxymethyl, oxo, -OH, and–CH2NH2, cycloalkyl,

cycloalkyl substituted with from one to five substituents

independently selected from:

fluoro,

chloro,

-OH,

C1-6alkyl, and

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro; heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro, C1-4alkoxy, and

-OH, or

R53ccr and R54ccr are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms independently

selected from O, N, and S, to form a heterocycloalkyl, which is optionally

substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, C1-4alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, -OH, -NH2, -N(H)C1-5alkyl, aminoheterocycloalkyl, -N(C1-5alkyl)2, -CN, -N(C1-4alkyl)(CH2OCH3), and -NHC1-4alkyl substituted by one or two substituents independently selected from oxo, NH2, and -OH,

heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents independently selected from: C1-6alkyl,

-C1-6alkylOH, fluoro, -C1-6alkylNH2,

chloro, oxo and -OH,

C1-4alkoxy,

C1-4alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

–CN,

oxo,

-OH, -OP(O)(OH)2,

-COOH,

-CONH2,

-NH2,

-N(H)C1-4alkyl,

-N(H)C1-6alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, C1-4alkoxy, oxo, phenyl, cycloalkyl,

aminoC1-4alkoxy, heterocycloalkyl,

methylheterocycloalkyl, -OH, -NH2, -N(H)C1-4alkyl, -N(C1-4alkyl)2, and–CN,

-Ooxetanyl,

-ONHC(NH)NH2,

-NHcyclopropyl,

-NHoxetanyl,

-N(C1-4alkyl)2,

-S(O)2CH2CH3, S(O)2CH2CH2CH3,

-S(O)2CH3,

-S(O)2phenyl,

benzoyl,

benzylamino,

-propylpyrrolidinyl,

-methylcyclopropyl,

cyclobutylamino,

cyclobutyl-N(CH3)-,

piperidinyl,

imidazolyl, morpholinyl,

morpholinylmethyl,

methylpiperazinylmethyl, methylpiperazinlyl

pyrrolidinyl,

pyrrolidinylmethyl,

(methoxypyridinylmethyl)amino,

methylpyrrolidinyl,

difluoropyrrolidinyl,

dimethylpyrrolidinyl,

(methylcyclopropylmethyl)amino,

hydroxymethylpyrrolidinyl, fluoropyrrolidinyl,

fluorophenylmethylamino, piperazinylmethyl,

oxazolidinyl,

(methyloxetanylmethyl)amino,

(methylcyclobutylmethyl)amino,

oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl;

provided that:

R53ccr and R54ccr are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

9. A compound according to claim 7 or claim 8 represented by the following Formula (VIccr):

wherein: Y6ccr is selected from: S and NH; R60ccr is selected from: C1-3alkyl,

C1-3alkyl substituted with from 1 to 6 substituents independently selected from: fluoro and chloro, -N(H)C1-3alkyl,

-N(C1-3alkyl)2, -SC1-4alkyl,

C1-3alkyloxy,

aryl,

aryl substituted with from one to 3 substituents

independently selected from:

fluoro,

chloro,

-OH, and

C1-3alkyl,

heteroaryl,

heteroaryl substituted with from one to 3 substituents independently selected from:

fluoro,

chloro,

-OH, and

C1-3alkyl,

cycloalkyl,

cycloalkyl substituted with from one to 3 substituents independently selected from:

fluoro,

chloro,

-OH, and C1-3alkyl;

R62ccr is selected from:

phenyl,

phenyl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

-CN,

oxo,

C1-4alkoxy,

C1-4alkoxy substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, oxo, -OH, -NH2, -NHCH3, and–N(CH3)2,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 5 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -S(O)2CH3, -CN, -OR69 and–NR66R67, where R66 and R67 are independently selected from: hydrogen, -S(O)2CH3, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR68R69, where R68 and R69 are independently selected from: hydrogen, phenyl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro and–COOH, tetrahydroisothiazolyl,

tetrahydroisothiazolyl substituted twice by oxo, tetrahydro-1,2-thiazinyl,

tetrahydro-1,2-thiazinyl substituted twice by oxo,

-N(CH3)S(O)2CFH2,

-N(CH3)S(O)2CF2H,

-N(CH3)S(O)2CF3,

-OS(O)2CH3,

-S(O)2NH2,

-S(O)2NHCH3, and

–NR80a’R81a’ where R80a’ and R81a’ are independently selected form: hydrogen, -S(O)2CH3, phenyl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituentsindependently selected from: fluoro, oxo, -OH, -NH2, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6

times by fluoro and–COOH,

hetroaryl, and

hetroaryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 5 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -S(O)2CH3, -CN, -OR69 and–NR66R67, where R66 and R67 are independently selected from: hydrogen, -S(O)2CH3, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR68R69, where R68 and R69 are independently selected from: hydrogen, phenyl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro and–COOH, -S(O)2NH2, and

-S(O)2NHCH3; and

R63ccr and R64ccr are independently selected from:

hydrogen,

C1-4alkyl,

C1-4alkyl substituted with from 1 to 4 substituents

independently selected from: phenyl, morpholino, triazolyl, imidazolyl, -CH2CH2pyrrolidinyl, -OC(O)NH2, -OCH2CH2NH2, -ONHC(NH2)NH2, -NHCH2C(CH3)3, -NOCH3, -NHOH, -NHCH2CH2F, -N(CH3)CH2CH2OCH3, -N(CH2CH3)2, -NCH(CH2OH)2, -N(CH2CH2OH)2, -NHCH2CH2OH, -NHCH2CH2NH2, -N(CH3)CH2(CH3)2CH2OH, -NHCH2CH3, -NHCH2CH2OCH3, -N(CH3)CH2CH2OH, -NHC(O)C(O)NH2, -N(CH3)CH2CH2CH2OH, -N(CH3)CH2CH(OH)CH2OH, -N(CH3)CH2CH2NH2, oxo, -NHCH2C(CH3)2CH2OH, -OH, -NH2, -NHCH3, -NHCH2CH2CH2OH, -N(CH3)2, -N(CH3)CH2CH3, -NHOC(CH3)2NH2, -N(CH3)CH2cyclopropyl, -NHCH2cyclopropyl, -NHoxetanyl, -NCH2CH2triazole, piperazinyl, piperidinyl, pyrazolyl, azepinyl, azetidinyl, methoxy, and cyclopropylamino,

where said phenyl, morpholino, triazolyl, imidazolyl, azepinyl, azetidinyl, pyrrolidinyl piperazinyl, piperidinyl, oxetanyl, cyclopropyl, and pyrazolyl are optionally substituted with from 1 to 4 substituents independently selected from: methyl, fluoro, -NH2, -N(CH3)2, hydroxymethyl, oxo, -OH, and–CH2NH2, cycloalkyl,

cycloalkyl substituted with from 1 to 5 substituents independently

selected from:

fluoro,

chloro,

-OH, and

C1-6alkyl,

heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

-OH, and

C1-6alkyl, or

R63ccr and R64ccr are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms independently selected from O, N, and S, to form a heterocycloalkyl, which is optionally

substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

-OH,

-OP(O)(OH)2,

-CN,

C1-6alkyl, C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, C1-4alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, -OH, -NH2, -N(H)C1-5alkyl, aminoheterocycloalkyl, -N(C1-5alkyl)2, -CN, -N(C1-4alkyl)(CH2OCH3), and -NHC1-4alkyl substituted by one or two substituents independently selected from oxo, NH2, and -OH,

heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents independently selected from: C1-6alkyl,

-C1-6alkylOH, fluoro, chloro, oxo and -OH, C1-4alkoxy,

C1-4alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–CN,

oxo,

-NH2, -N(H)C1-4alkyl,

-N(H)C1-6alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, C1-4alkoxy, oxo, phenyl, cycloalkyl,

aminoC1-4alkoxy, heterocycloalkyl,

methylheterocycloalkyl, -OH, -NH2, -N(H)C1-4alkyl, -N(C1-4alkyl)2, and–CN,

-ONHC(NH)NH2,

-Ooxetanyl,

-ONHC(NH)NH2,

-NHcyclopropyl,

-NHoxetanyl,

-N(C1-4alkyl)2,

-S(O)2CH2CH3,

S(O)2CH2CH2CH3,

-S(O)2CH3,

-S(O)2phenyl,

benzoyl,

benzylamino,

-propylpyrrolidinyl,

-methylcyclopropyl,

cyclobutylamino,

cyclobutyl-N(CH3)-,

piperidinyl,

imidazolyl,

morpholinyl,

morpholinylmethyl,

methylpiperazinylmethyl,

methylpiperazinyl, pyrrolidinyl,

pyrrolidinylmethyl,

(methoxypyridinylmethyl)amino, methylpyrrolidinyl,

difluoropyrrolidinyl,

dimethylpyrrolidinyl,

(methylcyclopropylmethyl)amino, hydroxymethylpyrrolidinyl,

fluoropyrrolidinyl,

(fluorophenylmethyl)amino,

piperazinylmethyl,

oxazolidinyl,

(methyloxetanylmethyl)amino,

(methylcyclobutylmethyl)amino, oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl;

provided that:

R63ccr and R64ccr are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

10. A compound according to anyone of claims 7 to 9 represented by the following Formula (Qc):

wherein:

R70ca’’ is selected from: ethyl,

-OCH3,

-CH2CF3, and

cyclopropyl;

R77ca’’ is selected from:

phenyl,

phenyl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

-CN,

oxo,

C1-4alkoxy,

C1-4alkoxy substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, oxo, -OH, -NH2, -NHCH3, and–N(CH3)2,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -S(O)2CH3, -CN, -OR79a’ and – NR76a’R77a’,

where R76a’ and R77a’ are independently selected form: hydrogen, -S(O)2CH3, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR78a’R79a’, where R78a and R79a are independently selected form: hydrogen, phenyl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituentsindependently selected from: fluoro, oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro and –COOH,

tetrahydroisothiazolyl,

tetrahydroisothiazolyl substituted twice by oxo, tetrahydro-1,2-thiazinyl,

tetrahydro-1,2-thiazinyl substituted twice by oxo,

-N(CH3)S(O)2CFH2,

-N(CH3)S(O)2CF2H,

-N(CH3)S(O)2CF3,

-OS(O)2CH3,

-S(O)2NH2, -S(O)2NHCH3, and –NR80a’R81a’ where R80a’ and R81a’ are independently selected form: hydrogen, -S(O)2CH3, phenyl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituentsindependently selected from: fluoro, oxo, -OH, -NH2, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6

times by fluoro and–COOH, and

R72ca’’ and R73ca’’ are independently selected from:

hydrogen, C1-4alkyl,

C1-4alkyl substituted with from 1 to 4 substituents

independently selected from: phenyl, morpholino, triazolyl, imidazolyl, -CH2CH2pyrrolidinyl, -OC(O)NH2, -OCH2CH2NH2, -ONHC(NH2)NH2, -NHCH2C(CH3)3, -NOCH3, -NHOH,

-NHCH2CH2F, -N(CH3)CH2CH2OCH3, -N(CH2CH3)2, -NCH(CH2OH)2, -N(CH2CH2OH)2, -NHCH2CH2OH,

-NHCH2CH2NH2, -N(CH3)CH2(CH3)2CH2OH, -NHCH2CH3, -NHCH2CH2OCH3, -N(CH3)CH2CH2OH, -NHC(O)C(O)NH2, -N(CH3)CH2CH2CH2OH, -N(CH3)CH2CH(OH)CH2OH,

-N(CH3)CH2CH2NH2, oxo, -NHCH2C(CH3)2CH2OH, -OH, -NH2, -NHCH3, -NHCH2CH2CH2OH, -N(CH3)2, -N(CH3)CH2CH3, -NHOC(CH3)2NH2, -N(CH3)CH2cyclopropyl, -NHCH2cyclopropyl, -NHoxetanyl, -NCH2CH2triazole, piperazinyl, piperidinyl, pyrazolyl, azepinyl, azetidinyl, methoxy, and cyclopropylamino,

where said phenyl, morpholino, triazolyl, imidazolyl, azepinyl, azetidinyl, pyrrolidinyl piperazinyl, piperidinyl, oxetanyl, cyclopropyl, and pyrazolyl are optionally substituted with from 1 to 4 substituents independently selected from: methyl, fluoro, -NH2, -N(CH3)2, hydroxymethyl, oxo, -OH, and–CH2NH2, cyclobutyl,

aminocyclobutyl,

tetrahydrofuran,

5-oxa-2azaspiro[3.4]octan, and

8-azabicyclo[3.2.1]octan, or

R72a’’ and R73a’’ are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms independently

selected from O, N, and S, to form a heterocycloalkyl selected from: pyrrolidinyl,

pyrrolo[3,4-c]pyrazolyl,

piperidinyl,

1,4diazepanyl,

piperazinyl,

6,7-dihydro-triazolo[4,5-c]pyridinyl,

2,9-diazaspiro[5.5]undecanyl,

2,8-diazaspiro[4.5]decanyl,

octahydro-1H-pyrrolo[1,2a][1,4]diazepinyl,

oxa-diazaspiro[4.5]decanyl,

oxazolyl,

morpholinyl,

1-oxa-6-azaspiro[3.4]octanyl,

2-oxa-6-azaspiro[3.4]octanyl,

1,7-diazaspiro[3.5]nonanyl,

2,7-diazaspiro[3.5]nonanyl,

2,6-diazaspiro[3.4]octanyl,

azetidinyl,

hexahydropyrrolo[3,4-b]oxazinyl,

dihydronaphthyridinyl,

diazabicycloheptanyl,

1,8-diazaspiro[4.5]decanyl, and

5-oxa-2-azaspiro[3.4]octanyl,

all of which are optionally substituted with from 1 to 5

substituents independently selected from:

fluoro,

chloro,

oxo,

-OH,

-OP(O)(OH)2,

-CN, -CH3,

-CH2OH,

methoxy,

-CH2CH3,

-C(O)CH3,

-C(O)NH2,

-OCH2CH2OH,

-OCH2CH2NH2,

-ONHC(NH)NH2,

-OC(O)NH2,

-Ooxetanyl,

-CH2CH2OH,

-CH2CH2CH2OH, -CH2CH2CH3,

-CH2CH2OCH3,

-CH2CH(OH)CH3, -CH2CH(OH)CH2OH, -CH2C(O)OCH3,

-CH2C(O)NH2,

-C(O)CH(CH3)2,

-CH2CH2N(CH3)2, -CH2CH2NHCH2CH3, -CH2CH2CH2N(CH3)2, -CH2CH2NHCH2C(CH3)3, -CH2CH2N(CH3)CH2OCH3, -C(CH3)2CH2OH,

-CH2C(CH3)2OH, -CH2C(CH3)2OCH3, -C(O)CH2OH,

-CH2isothiazolyl,

-CH2thiazolyl,

-CH2pyrazolyl,

-CH2imidazolyl,

-CH2pyridinyl,

-CH2oxazolyl,

-CH2pyrrolyl,

-CH2pyrrolidinyl, -CH2isoxazoly,

-CH2furanyl,

-CH2CH2morpholinyl, -CH2CH2pyrrolidinyl, -CH2CH2pyrrolidinylCH3, -CH2CH2CH2pyrrolidinyl, -C(O)phenyl,

-C(O)C(tetrahydropyranyl)NH2, -NH2,

-NHCH3,

-N(CH3)2,

-NHC(O)CH3, -NHCH(CH3)2,

-NHCH2CHF2, -NHCH2C(CH3)3, -NHCH2CH(CH3)2, -NHCH2CH2OCH3, -NHCH2CH2OH, -NHCH2CH2NH2, -NHCH2C(O)OH, -NHC(O)CH2NH2, -NHC(O)CH2CH2CH2NH2, -NHCH2C(O)NH2, -NHCH2C(OH)(CH3)2, -NHC(O)CH(CH3)NH2, -NHC(O)OCH(CH3)NH2, -NHC(O)CH(CH3)2, -NHC(O)C(CH3)3, -NHC(O)C(CH3)2NH2, -NHC(O)CH2OH, -NHC(O)CH(CH2OH)NH2, -NHC(O)(oxetanyl)NH2, -NHC(O)OC(CH3)3, -NHC(CH3)2C(O)OCH3, -NHcyclopropyl,

-NHoxetanyl,

-CH2NH2, -CH2CH2NH2, -CH2CH2CH2NH2, -CH2NHCH2C(CH3)3, -CH2NHC(O)C(CH3)3, -CH2NHC(O)CH2NH2, -CH2NHC(O)CH2OH, -CH2N(CH3)2, -CH2NHCH3,

-CH2N(CH2CH3)2, -CH2CH2N(CH3)2, -S(O)2CH2CH3, -S(O)2CH2CH2CH3, -S(O)2phenyl, -S(O)2CH3, benzoyl,

benzylamino,

-propylpyrrolidinyl, -methylcyclopropyl, cyclobutylamino, cyclobutyl-N(CH3)-, piperidinyl, imidazolyl, morpholinyl, morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinyl, pyrrolidinyl, pyrrolidinylmethyl, (methoxypyridinylmethyl)amino,

methylpyrrolidinyl,

difluoropyrrolidinyl,

dimethylpyrrolidinyl,

(methylcyclopropylmethyl)amino,

hydroxymethylpyrrolidinyl,

fluoropyrrolidinyl,

(fluorophenylmethyl)amino,

piperazinylmethyl,

oxazolidinyl,

(methyloxetanylmethyl)amino,

(methylcyclobutylmethyl)amino,

oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl;

provided that:

R72a’’ and R73a’’ are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

11. A compound of claim 7 selected from:

N-(4-((3,5-Dicyano-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1-yl)pyridin-2- ylthio)methyl)benzyl)acetamide;

2-(4-(Aminomethyl)benzylthio)-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1-yl)pyridine- 3,5-dicarbonitrile;

tert-Butyl4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzylcarbamate;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzamide;

2-((4-(Aminomethyl)benzyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridine- 3,5-dicarbonitrile; 2-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)acetic acid;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzoic acid;

2-(Dimethylamino)-4-ethyl-6-(((6-oxo-1,6-dihydropyridin-3-yl)methyl)thio)pyridine- 3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)thiazol-2-yl)acetamide;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzenesulfonamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl) acetamide;

tert-Butyl(2-((4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)amino)-2-oxoethyl)carbamate;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)methanesulfonamide;

2-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)acetamide;

2-(4-Aminopiperidin-1-yl)-6-(benzylthio)-4-ethylpyridine-3, 5-dicarbonitrile; 4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl acetate;

2-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl acetamide;

2-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylacetamide;

4-Ethyl-2-((4-(hydroxymethyl)benzyl)thio)-6-(4-methyl-1,4-diazepan-1-yl)pyridine- 3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)-2-hydroxyacetamide;

Example 87N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2-yl)thio) methyl)benzyl)propionamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)isobutyramide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)-3-methylbutanamide;

4-Ethyl-2-((4-(((2-hydroxyethyl)amino)methyl)benzyl)thio)-6-(4-methyl-1,4- diazepan-1-yl)pyridine-3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-6-(4-methyl-1,4-diazepan-1-yl)-4-(methylamino)pyridin-2- yl)thio)methyl)benzyl)acetamide;

2-(((2-Acetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)methyl)thio)-6-(dimethylamino)-4- ethylpyridine-3,5-dicarbonitrile;

2-((4-Cyanobenzyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridine-3,5- dicarbonitrile;

2-Amino-N-(1-(6-(benzylthio)-3,5-dicyano-4-ethylpyridin-2-yl)piperidin-4- yl)acetamide;

2-Amino-N-(1-(6-(benzylthio)-3,5-dicyano-4-ethylpyridin-2-yl)piperidin-4-yl)-2- methylpropanamide;

3-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)propanamide;

(S)-2-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)propanamide;

Example 98(R)-2-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1- yl)pyridin-2-yl)thio)methyl)benzyl)propanamide; 1-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2-yl)thio)m ethyl)benzyl)-3-ethylurea;

1-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)-3-phenylurea;

N-(4-(((3,5-Dicyano-6-(4-methyl-1,4-diazepan-1-yl)-4-(methylthio)pyridin-2- yl)thio)methyl)benzyl)acetamide; (E)-3-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2- yl)thio)methyl)phenyl)acrylic acid;

N-(4-(((3,5-Dicyano-4-ethyl-6-((2-hydroxyethyl)(methyl)amino)pyridin-2- yl)thio)methyl)benzyl)acetamide;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2-yl)thio)methyl)-N- methylbenzenesulfonamide;

N-(4-(((3,5-Dicyano-4-ethoxy-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)acetamide;

N-(4-(((6-(4-Aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2- yl)thio)methyl)benzyl)acetamide;

(S)-2-((1-(6-((4-(Acetamidomethyl)benzyl)thio)-3,5-dicyano-4-ethylpyridin-2- yl)piperidin-4-yl)oxy)ethyl 2-amino-3-methylbutanoate;

(S)-2-((6-((4-(Acetamidomethyl)benzyl)thio)-3,5-dicyano-4-ethylpyridin-2- yl)(methyl)amino)ethyl 2-amino-3-methylbutanoate;

2-Amino-N-(4-(((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2- yl)thio)methyl)benzyl)acetamide;

4-Ethyl-2-(4-methyl-1,4-diazepan-1-yl)-6-((4-((2-oxopyrrolidin-1- yl)methyl)benzyl)thio)pyridine-3,5-dicarbonitrile;

2-((4-(Aminomethyl) benzyl)thio)-6-(dimethylamino)-4-ethylpyridine-3,5- dicarbonitrile;

N-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl) thio) methyl) phenyl) acetamide;

N-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)methyl)benzyl)-2- hydroxyacetamide;

3-Amino-N-(4-(((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2- yl)thio)methyl)benzyl)propanamide;

(S)-1-(6-((4-(Acetamidomethyl)benzyl)thio)-3,5-dicyano-4-ethylpyridin-2- yl)azetidin-3-yl 2-amino-3-methylbutanoate;

N-(4-(((3,5-Dicyano-4-ethyl-6-methylpyridin-2-yl)thio)methyl)benzyl)acetamide; 2-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)methyl)-1H-pyrazol- 1-yl)acetamide;

N-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)methyl)phenyl) methanesulfonamide;

(S)-1-(6-((4-(Acetamidomethyl)benzyl)thio)-3,5-dicyano-4-ethylpyridin-2- yl)piperidin-4-yl 2-amino-3-methylbutanoate;

N-(1-(6-((4-(Acetamidomethyl)benzyl)thio)-3,5-dicyano-4-ethylpyridin-2- yl)piperidin-4-yl)acetamide;

2-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)methyl)phenyl)-N-(2- hydroxyethyl)acetamide;

4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)methyl)-N-(2- hydroxyethyl)benzamide;

2-((4-(1H-Imidazol-1-yl)benzyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridine- 3,5-dicarbonitrile;

2-((4-Cyano-3-methylbenzyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridine- 3,5-dicarbonitrile;

tert-Butyl (4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)carbamate;

2-((4-Aminobenzyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridine-3,5- dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)acetamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl) methanesulfonamide;

2-(((6-Aminopyridin-3-yl)methyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1- yl)pyridine-3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)-2-hydroxyacetamide;

2-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)acetamide; N-(4-(((3,5-Dicyano-4-ethyl-6-(3-oxopiperazin-1-yl)pyridin-2-yl)thio) methyl) benzyl) acetamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(3-hydroxypyrrolidin-1-yl)pyridin-2- yl)thio)methyl)benzyl)acetamide;

N-(4-(1-(3,5-Dicyano-6-(4-(dimethylamino)piperidin-1-yl)-4-ethylpyridin-2- ylthio)propyl)benzyl)acetamide;

N-(5-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)pyridin-2-yl)methanesulfonamide;

2-(6-(4-(Acetamidomethyl)benzylthio)-3,5-dicyano-4-ethylpyridin-2-ylthio)-2- phenylacetamide;

4-Ethyl-2-((4-(pyridin-3-yl)benzyl)thio)-6-(4-(pyrrolidin-1-yl)piperidin-1-yl)pyridine- 3,5-dicarbonitrile;

4-Ethyl-2-((4-(pyridin-4-yl)benzyl)thio)-6-(4-(pyrrolidin-1-yl)piperidin-1-yl)pyridine- 3,5-dicarbonitrile;

2-Amino-N-(1-(3,5-dicyano-4-ethyl-6-((4-sulfamoylbenzyl)thio)pyridin-2- yl)piperidin-4-yl)acetamide;

2-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-(2-hydroxyethyl)acetamide;

2-(((1H-Indol-5-yl)methyl)thio)-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1-yl)pyridine- 3,5-dicarbonitrile;

4-(((6-(4-Aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-yl)thio)methyl) benzenesulfonamide;

2-((Benzo[d][1,3]dioxol-5-ylmethyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1- yl)pyridine-3,5-dicarbonitrile;

2-(((3,3-Dimethoxy-2-oxoindolin-5-yl)methyl)thio)-4-ethyl-6-(4-methyl-1,4- diazepan-1-yl)pyridine-3,5-dicarbonitrile;

2-(((2,3-Dioxoindolin-5-yl)methyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1- yl)pyridine-3,5-dicarbonitrile;

N-(4-(((6-(((4H-1,2,4-Triazol-3-yl)methyl)(methyl)amino)-3,5-dicyano-4- ethylpyridin-2-yl)thio)methyl)benzyl)acetamide; 4-Ethyl-2-((4-(pyridin-2-yl)benzyl)thio)-6-(4-(pyrrolidin-1-yl)piperidin-1-yl)pyridine- 3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylacetamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2-yl) thio)methyl)phenyl)-N-methylmethanesulfonamide;

4-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- ylthio)methyl)phenylboronic acid;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)benzyl)-2-(methylamino)acetamide;

2-((4-Amino-3-fluorobenzyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridine- 3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2-yl)thio)methyl)- 2-fluorophenyl)methanesulfonamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2-yl) thio)methyl)-2-fluorophenyl)acetamide;

2-(4-Aminopiperidin-1-yl)-4-ethyl-6-(((1-(2-hydroxyethyl)-1H-pyrazol-4- yl)methyl)thio)pyridine-3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(3-hydroxypyrrolidin-1-yl)pyridin-2- yl)thio)methyl)benzyl)-2-hydroxyacetamide;

N-(4-(((6-((2-Amino-2-oxoethyl) (methyl) amino)-3, 5-dicyano-4-ethylpyridin-2-yl) thio) methyl) benzyl)-2-hydroxyacetamide;

2-(4-(2-(Dimethylamino)ethoxy)benzylthio)-4-ethyl-6-(4-methyl-1,4-diazepan-1- yl)pyridine-3,5-dicarbonitrile;

4-Ethyl-2-(4-methyl-1,4-diazepan-1-yl)-6-((4-(methylsulfonyl)benzyl)thio)pyridine- 3,5-dicarbonitrile;

2-(4-Aminopiperidin-1-yl)-6-(((1-(2,3-dihydroxypropyl)-1H-pyrazol-4-yl)methyl)thio)- 4-ethylpyridine-3,5-dicarbonitrile;

4-Ethyl-2-(4-methyl-1,4-diazepan-1-yl)-6-((4-(4-methylpiperazin-1- yl)benzyl)thio)pyridine-3,5-dicarbonitrile; 4-Ethyl-2-(4-methyl-1,4-diazepan-1-yl)-6-((4-(((2-oxopyrrolidin-3- yl)amino)methyl)benzyl)thio)pyridine-3,5-dicarbonitrile;

2-(((1H-Benzo[d]imidazol-5-yl)methyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1- yl)pyridine-3,5-dicarbonitrile;

4-Ethyl-2-(4-methyl-1,4-diazepan-1-yl)-6-(4- (methylsulfonylmethyl)benzylthio)pyridine-3,5-dicarbonitrile;

2-{[3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl]sulfanyl}-2-phenylacetamide; N-(4-(((3,5-dicyano-4-ethyl-6-(methyl(2-(neopentylamino)ethyl)amino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-((2-((2- methoxyethyl)(methyl)amino)ethyl)(methyl)amino)pyridin-2-yl)thio)methyl)phenyl)-N- methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(methyl(2-(methylamino)ethyl)amino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-((2-((2- methoxyethyl)amino)ethyl)(methyl)amino)pyridin-2-yl)thio)methyl)phenyl)-N- methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(methyl(2-((1- methylcyclopropyl)amino)ethyl)amino)pyridin-2-yl)thio)methyl)phenyl)-N- methylmethanesulfonamide;

N-(4-(((3,5-dicyano-6-((2-(dimethylamino)ethyl)(methyl)amino)-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((6-((2-aminoethyl)(methyl)amino)-3,5-dicyano-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

2-(4-aminopiperidin-1-yl)-4-ethyl-6-((4- ((methylsulfonyl)methyl)benzyl)thio)pyridine-3,5-dicarbonitrile;

N-(4-(((3,5-dicyano-4-ethyl-6-((2-((2-fluoroethyl)amino)ethyl)(methyl)amino)pyridin- 2-yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

2-amino-N-(4-(((3,5-dicyano-6-((2-(diethylamino)ethyl)(methyl)amino)-4- ethylpyridin-2-yl)thio)methyl)benzyl)acetamide; 4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2-yl)thio)methyl)-N- (1H-pyrazol-4-yl)benzamide;

rel-2-amino-N-(4-(((6-(cis-4-amino-3-fluoropiperidin-1-yl)-3,5-dicyano-4- ethylpyridin-2-yl)thio)methyl)benzyl)acetamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-(isopropylamino)piperidin-1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-((2-methoxyethyl)amino)piperidin-1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-(neopentylamino)piperidin-1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(methyl(2-(pyrrolidin-1-yl)ethyl)amino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-6-(2-((dimethylamino)methyl)morpholino)-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

2-amino-N-(1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)piperidin-4-yl)-2-methylpropanamide;

N-(4-(((3,5-dicyano-6-(4-(cyclopropylamino)piperidin-1-yl)-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(2-(pyrrolidin-1-ylmethyl)morpholino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(methyl(2-(piperidin-1-yl)ethyl)amino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-6-((2-(diethylamino)ethyl)(methyl)amino)-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-6-(2-((diethylamino)methyl)morpholino)-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

(R)-2-amino-N-(1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)piperidin-4-yl)propanamide; (S)-2-amino-N-(1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)piperidin-4-yl)propanamide;

N-(4-(((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

2-amino-N-(1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)piperidin-4-yl)acetamide;

N-(4-(((6-(2-(aminomethyl)morpholino)-3,5-dicyano-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)-1-fluoro-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(2-((methylamino)methyl)morpholino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-6-(3-((dimethylamino)methyl)piperidin-1-yl)-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

2-(4-aminopiperidin-1-yl)-6-((4-(1,1-dioxidoisothiazolidin-2-yl)benzyl)thio)-4- ethylpyridine-3,5-dicarbonitrile;

2-(4-aminopiperidin-1-yl)-6-((4-(1,1-dioxido-1,2-thiazinan-2-yl)benzyl)thio)-4- ethylpyridine-3,5-dicarbonitrile;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridin-2- yl)thio)methyl)phenyl)-1,1-difluoro-N-methylmethanesulfonamide;

2-((4-(1,1-dioxidoisothiazolidin-2-yl)benzyl)thio)-4-ethyl-6-(4- (neopentylamino)piperidin-1-yl)pyridine-3,5-dicarbonitrile;

2-((4-(1,1-dioxido-1,2-thiazinan-2-yl)benzyl)thio)-4-ethyl-6-(4- (neopentylamino)piperidin-1-yl)pyridine-3,5-dicarbonitrile;

4-(((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-yl)thio)methyl)phenyl methanesulfonate;

(R)-2-amino-N-((1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)pyrrolidin-3-yl)methyl)acetamide;

(S)-2-amino-N-((1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)pyrrolidin-3-yl)methyl)acetamide; N-(4-(1-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2- yl)thio)ethyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-methoxypyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide; and

N-(4-(((3,5-dicyano-4-ethyl-6-(4-((2-hydroxyethyl)amino)piperidin-1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide; or a pharmaceutically acceptable salt or prodrug thereof. 12. A pharmaceutical composition comprising a compound according to any one of claims 7 to 11 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient. 13. A method of treating a disease selected from: cancer, pre-cancerous syndromes, beta haemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, in a mammal in need thereof, which comprises administering to such mammal a therapeutically effective amount of a compound as described in any one of claims 7 to 11 or a pharmaceutically acceptable salt thereof. 14. The method of claim 13 wherein the mammal is a human. 15. A method of treating a disease selected from: cancer, pre-cancerous syndromes, beta haemoglobinopathy disordes, sickle cell disease, sickle cell anemia, and beta thalassemia, in a mammal in need thereof, which comprises administering to such mammal a therapeutically effective amount of a compound of claim 11 or a pharmaceutically acceptable salt thereof. 16. The method of claim 15 wherein the mammal is a human. 17. The method according to claim 14 wherein said cancer is selected from: brain (gliomas), glioblastomas, astrocytomas, glioblastoma multiforme, Bannayan-Zonana syndrome, Cowden disease, Lhermitte-Duclos disease, breast, colon, head and neck, kidney, lung, liver, melanoma, ovarian, pancreatic, adenocarcinoma, ductal adenocarcinoma, adenosquamous carcinoma, acinar cell carcinoma, glucagonoma, insulinoma, prostate, sarcoma and thyroid.

18. The method according to claim 16 wherein: said cancer is selected from brain (gliomas), glioblastomas, astrocytomas, glioblastoma multiforme, Bannayan-Zonana syndrome, Cowden disease, Lhermitte-Duclos disease, breast, colon, head and neck, kidney, lung, liver, melanoma, ovarian, pancreatic, adenocarcinoma, ductal adenocarcinoma, adenosquamous carcinoma, acinar cell carcinoma, glucagonoma, insulinoma, prostate, sarcoma and thyroid. 19. Use of a compound as described in any one of claims 7 to 11 or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in treating or lessening the severity of cancer. 20. A method of inhibiting DNMT1 activity in a mammal in need thereof, which comprises administering to such mammal a therapeutically effective amount of a compound as described in any one of claims 7 to 11 or a pharmaceutically acceptable salt thereof. 21. The method of claim 20 wherein the mammal is a human. 22. A method of treating cancer in a mammal in need thereof, which comprises: administering to such mammal a therapeutically effective amount of

a) a compound of as described in any one of claims 7 to 11 or a pharmaceutically acceptable salt thereof; and

b) at least one anti-neoplastic agent. 23. The method claim 22, wherein the at least one anti-neoplastic agent is selected from the group consisting of: anti-microtubule agents, platinum coordination complexes, alkylating agents, antibiotic agents, topoisomerase II inhibitors, antimetabolites, topoisomerase I inhibitors, hormones and hormonal analogues, signal transduction pathway inhibitors, non-receptor tyrosine kinase angiogenesis, inhibitors, immunotherapeutic agents, proapoptotic agents, cell cycle signaling inhibitors, proteasome inhibitors, inhibitors of cancer metabolism, anti-PD-L1 agents, PD-1 antagonist, immuno- modulators, STING modulating compounds, CD39 inhibitors, A2a and A2a adenosine antagonists, TLR4 antagonists, antibodies to ICOS, and antibodies to OX40. 24. A pharmaceutical combination comprising:

a) a compound as described in any one of claims 7 to 11 or a pharmaceutically acceptable salt thereof; and

b) at least one anti-neoplastic agent.

25. A pharmaceutical combination as claimed in claim 24 for use in the treatment of cancer. 26. The method according to claim 13 wherein said cancer is selected from: breast cancer, inflammatory breast cancer, ductal carcinoma, lobular carcinoma, colon cancer, pancreatic cancer, insulinomas, adenocarcinoma, ductal adenocarcinoma, adenosquamous carcinoma, acinar cell carcinoma, glucagonoma, skin cancer, melanoma, metastatic melanoma, lung cancer, small cell lung cancer, non-small cell lung cancer, squamous cell carcinoma, adenocarcinoma, large cell carcinoma, brain (gliomas), glioblastomas, astrocytomas, glioblastoma multiforme, Bannayan-Zonana syndrome, Cowden disease, Lhermitte-Duclos disease, Wilm's tumor, Ewing's sarcoma, Rhabdomyosarcoma, ependymoma, medulloblastoma, head and neck, kidney, liver, melanoma, ovarian, pancreatic, adenocarcinoma, ductal adenocarcinoma, adenosquamous carcinoma, acinar cell carcinoma, glucagonoma, insulinoma, prostate, sarcoma, osteosarcoma, giant cell tumor of bone, thyroid,

lymphoblastic T cell leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, hairy-cell leukemia, acute lymphoblastic leukemia, acute myelogenous leukemia, chronic neutrophilic leukemia, acute lymphoblastic T cell leukemia, plasmacytoma, Immunoblastic large cell leukemia, mantle cell leukemia, multiple myeloma, megakaryoblastic leukemia, multiple myeloma, acute megakaryocytic leukemia, promyelocytic leukemia, erythroleukemia,

malignant lymphoma, hodgkins lymphoma, non-hodgkins lymphoma, lymphoblastic T cell lymphoma, Burkitt’s lymphoma, follicular lymphoma,

neuroblastoma, bladder cancer, urothelial cancer, vulval cancer, cervical cancer, endometrial cancer, renal cancer, mesothelioma, esophageal cancer, salivary gland cancer, hepatocellular cancer, gastric cancer, nasopharangeal cancer, buccal cancer, cancer of the mouth, GIST (gastrointestinal stromal tumor), neuroendocrine cancers and testicular cancer. 27. The method of claim 26 wherein the mammal is a human. 28. . A process for preparing a pharmaceutical composition containing a pharmaceutically acceptable excipient and an effective amount of a compound of Formula (IVccr), (Vccr), (VIccr), or (Qc) as described in any one of claims 7 to 11 or a pharmaceutically acceptable salt thereof, which process comprises bringing the compound of Formula (IVccr), (Vccr), (VIccr), or (Qc) or a pharmaceutically acceptable salt thereof into association with a pharmaceutically acceptable excipient. 29. The method according to claim 14 wherein said pre-cancerous syndrome is selected from: cervical intraepithelial neoplasia, monoclonal gammapathy of unknown significance (MGUS), myelodysplastic syndrome, aplastic anemia, cervical lesions, skin nevi (pre-melanoma), prostatic intraepithleial (intraductal) neoplasia (PIN), Ductal Carcinoma in situ (DCIS), colon polyps and severe hepatitis or cirrhosis. 30. A pharmaceutical combination comprising:

a) a compound as described in any one of claims 7 to 11 or a pharmaceutically acceptable salt thereof; and

b) at least one agent useful for treating beta haemoglobinopathies. 31. A pharmaceutical combination as claimed in claim 30 for use in treating sickle cell disease. 32. A pharmaceutical combination as claimed in claim 30 for use in treating sickle cell anemia. 33. A pharmaceutical combination as claimed in claim 30 for use in treating beta- thalassemia. 34. A method of treating a disease selected from: diabetic nephropathy, diabetes, podocyte injury, atherosclerosis, psoriasis, idiopathic pulmonary fibrosis, scleroderma, liver cirrhosis, rheumatoid arthritis, and Alzheimer’s disease, in a mammal in need thereof, which comprises administering to such mammal a therapeutically effective amount of a compound as described in any one of claims 7 to 11 or a pharmaceutically acceptable salt thereof.

35. The method of claim 34 wherein the mammal is a human. 36. A pharmaceutical composition comprising from 0.5 to 1,000 mg of a compound or pharmaceutically acceptable salt thereof as defined in any one of claims 1, 2 or 6, and from 0.5 to 1,000 mg of a pharmaceutically acceptable excipient.

Description:
CHEMICAL COMPOUNDS FIELD OF THE INVENTION

The present invention relates to substituted pyridine derivatives that are selective inhibitors of the activity of DNA methyltransferase1 (DNMT1). The present invention also relates to pharmaceutical compositions comprising such compounds and methods of using such compounds in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anaemia, and beta thalassemia, and other diseases associated with DNMT1 inhibition. BACKGROUND OF THE INVENTION

Epigenetics is a way to turn genes on and off independent of the underlaying DNA sequence. DNA methylation occurring in gene promotors is an example of a repressive epigenetic mark resulting in chromatin compaction and gene silencing. DNA methylation is mediated by the DNA methyltransferase (DNMT) family of proteins which is comprised of four family members. Three of the family members, DNMT1, DNMT3A and DNMT3B, contain DNA methyltransferase activity. These three members are responsible for establishing the de novo DNA methylation pattern, while DNMT1 is primarily responsible for maintaining the methylation pattern in daughter strands following DNA replication. In cancer, DNA methylation patterns become aberrant resulting in global hypomethylation and localized hypermethylation within promoter regions. This can result in downstream silencing of tumor suppressor genes (Ting et al. Genes Dev.2006;

20:3215-3231). Additionally, silencing of DNMT1 results in DNA demethylation and reexpression of tumor suppressor genes resulting in tumor growth inhibition (Zhou et al. Oncol. Lett.2014; 5: 2130– 2134). DNA methylation inhibitors (termed DNA hypomethylating agents) are clinically validated anti-cancer therapies utilized for the treatment of MDS, AML and CMML. While these agents are available, there is still significant opportunity for improvement regarding toxicity, utility in solid tumors and oral bioavailability. Hence, a novel DNMT inhibitor would be of interest for the treatment of cancer and/or any disease or condition mediated by DNA methylation. Of particular interest to this invention, is specifically targeting DNMT1 to prevent propagation of abnormal methylation patterns (such as those that occur in cancer) to daughter strands during replication. US 2008/0132525 and WO 2006/078752 describe inhibitors of DNA

methyltransferase. CA 2030875 describes methods and probes for detecting nucleoside transporter and method for producing the probes. Hemoglobinopathies

Hemoglobin disorders, such as sickle cell anemia and beta-thalassaemia, represent the most common heritable blood diseases in the world. Sickle cell anemia and beta-thalassemia are characterized by disorders of hemoglobin, which is the oxygen carrying protein complex in red blood cells. Structurally, hemoglobin is normally composed of two pairs of proteins plus four molecules of heme. Adults and children older than about four months, express a form of hemoglobin referred to as adult hemoglobin, which predominantly consists of two alpha-globin proteins paired with two beta-globin proteins plus four molecules of heme. However, fetuses and infants typically express mostly fetal hemoglobin, which is composed of two alpha-globin proteins paired with two gamma-globin proteins plus four molecules of heme. Note that there are two forms of gamma-globin, termed G-gamma and A-gamma, that are encoded by two different genes (HBG1 and HBG2) but that are functionally equivalent to a large degree; fetal hemoglobin refers to any combination of a pair of G-gamma and/or A-gamma plus a pair of alpha- globin proteins plus four molecules of heme. In sickle cell anemia, the gene encoding for beta-globin contains a mutation which results in an abnormal hemoglobin structure and causes red blood cells to adopt a characteristic sickle shape under certain conditions. This sickle shape leads to reduced red cell plasticity, longer capillary transit times, and frequent vaso-occlusive processes that can damage tissues and result in patient morbidity. In contrast, beta-thalassemia is characterized by inadequate beta-globin production to combine with normally produced alpha-globin. The resulting accumulation of alpha globin is toxic to red blood cell precursors, and results in ineffective erythropoiesis and extensive red blood cell hemolysis. There is currently no approved pharmacologic treatment to cure sickle cell anemia or beta-thalassemia. However, increases in the number of red blood cells that produce fetal hemoglobin, combined with overall increases in the level of fetal hemoglobin per red blood cell have been proven to provide clinical benefit in sickle cell anemia and sickle cell disease patients by reducing the frequency of acute vaso-occlusive crises. Additionally, although not clinically proven, the disease biology of beta-thalassemia suggests that increasing fetal hemoglobin production to high levels may be a viable strategy for the therapy of this disease as well. The object of this therapeutic approach, the de-repression of the silenced HBG1 and HBG2 genes, may be targeted through intervention in an epigenetic process in erythropoiesis. Changes in DNA methylation are key determining events in the course of hematopoiesis, marking differentiation milestones that result in commitments to various cell lineages. During erythropoiesis, a rapid decrease in global DNA methylation demarks a commitment point toward the expression of erythroid specific regulators GATA1 and KLF1, and suppression of hematopoietic progenitor regulators GATA2 and PU.1 (1, 2). For erythroid progenitor cells in adult bone marrow, DNA in the promoter region of the beta-globin HBB gene becomes unmethylated, corresponding to high level expression of beta-globin protein. In contrast, promoters of the HBG1 and HBG2 loci are highly methylated, resulting in greatly diminished expression of gamma-globin proteins (3). Although DNA methyltransferases DNMT1, DNMT3A, and DNMT3B are each expressed in erythroid progenitors, the relatively greater expression of DNMT1, particularly in the final stages of erythroid differentiation suggests that it plays a dominant role in globin gene regulation (2). 5-azacytidine and 5-aza-2’-deoxycytidine (decitabine) are pan-DNMT inhibitors that are known inducers of fetal hemoglobin in erythroid progenitor cells. In erythroid cell culture and in an in vivo model of fetal hemoglobin induction (4, 5), treatment with these agents causes decreased methylation of CpG sites in the HBG promoters with corresponding increases in the gamma globin protein expression.

Moreover, in a limited set of clinical studies, both agents caused increases in fetal hemoglobin in patients with sickle cell anemia, sickle cell disease and beta-thalassemia (6-9). While effective at inducing fetal hemoglobin, these agents have not been widely used to treat sickle cell anemia, sickle cell disease, or beta-thalassemia due to concerns over long-term safety, dose-limiting toxicities, and an unsuitable dosing route. References (1) Pop R, Shearstone JR, Shen Q, Liu Y, Hallstrom K, Koulnis M, et al. A key commitment step in erythropoiesis is synchronized with the cell cycle clock through mutual inhibition between PU.1 and S-phase progression.2010;8.

(2) Shearstone JR, Pop R, Bock C, Boyle P, Meissner A, Socolovsky M. Global DNA demethylation during mouse erythropoiesis in vivo.2011;334:799-802. (3) Mabaera R, Richardson CA, Johnson K, Hsu M, Fiering S, Lowrey CH. Developmental- and differentiation-specific patterns of human +¦- and +¦-globin promoter DNA methylation.2007;110:1343-52.

(4) Chin J, Singh M, Banzon V, Vaitkus K, Ibanez V, Kouznetsova T, et al.

Transcriptional activation of the +¦-globin gene in baboons treated with decitabine and in cultured erythroid progenitor cells involves different mechanisms. 2009;37:1131-42.

(5) Akpan I, Banzon V, Ibanez V, Vaitkus K, DeSimone J, Lavelle D. Decitabine increases fetal hemoglobin in Papio anubis by increasing +¦-globin gene transcription.2010;38:989-93.

(6) Dover GJ, Charache SH, Boyer SH, Talbot J, Smith KD. 5-Azacytidine increases fetal hemoglobin production in a patient with sickle cell disease.1983;134:475-88. (7) Saunthararajah Y, Hillery CA, Lavelle D, Molokie R, Dorn L, Bressler L, et al. Effects of 5-aza-2GǦ-deoxycytidine on fetal hemoglobin levels, red cell adhesion, and hematopoietic differentiation in patients with sickle cell disease.2003;102:3865-70. (8) Ley TJ, DeSimone J, Noguchi CT, Turner PH, Schechter AN, Heller P, et al. 5- Azacytidine increases +¦-globin synthesis and reduces the proportion of dense cells in patients with sickle cell anemia.1983;62:370-80.

(9) Lowrey CH, Nienhuis AW. Brief report: Treatment with azacitidine of patients with end-stage +¦- thalassemia.1993;329:845-8.

It is an object of the present invention to provide novel compounds that are selective inhibitors of DNMT1. It is also an object of this invention to provide compounds which increase the production of gamma globin, and thereby also increase the production of fetal hemoglobin in human erythroid cells. The compounds of this invention may therefore be useful to treat sickle cell anemia and sickle cell disease. Beta-thalassemia may also be ameliorated by treatment with these compounds. It is also an object of the present invention to provide pharmaceutical compositions that comprise a pharmaceutical excipient and compounds of Formula (I). It is also an object of the present invention to provide a method for treating cancer, pre-cancerous syndromes, beta hemoglobinopathies, such as sickle cell disease, sickle cell anaemia, and beta thalassemia, that comprises administering novel selective inhibitors of DNMT1 activity. SUMMARY OF THE INVENTION

The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar):

w herein Y ar , X 1ar , X 2ar , R 1ar , R 2ar , R 3ar , R 4ar and R 5ar are as defined below; or a pharmaceutically acceptable salt or prodrug thereof. The present invention also relates to the discovery that the compounds of Formula (I) are active as inhibitors of DNMT1, and selective against DNMT3A and DNMT3B. This invention also relates to a method of treating cancer, which comprises administering to a subject in need thereof an effective amount of a DNMT1 inhibiting compound of Formula (I); or a pharmaceutically acceptable salt thereof. This invention also relates to a method of treating pre-cancerous syndromes, which comprises administering to a subject in need thereof an effective amount of a DNMT1 inhibiting compound of Formula (I); or a pharmaceutically acceptable salt thereof. This invention also relates to a method of treating beta hemoglobinopathies, which comprises administering to a subject in need thereof an effective amount of a DNMT1 inhibiting compound of Formula (I); or a pharmaceutically acceptable salt thereof. This invention also relates to a method of treating sickle cell disease, which comprises administering to a subject in need thereof an effective amount of a DNMT1 inhibiting compound of Formula (I); or a pharmaceutically acceptable salt thereof. This invention also relates to a method of treating sickle cell anemia, which comprises administering to a subject in need thereof an effective amount of a DNMT1 inhibiting compound of Formula (I); or a pharmaceutically acceptable salt thereof. This invention also relates to a method of treating beta thalassemia, which comprises administering to a subject in need thereof an effective amount of a DNMT1 inhibiting compound of Formula (I); or a pharmaceutically acceptable salt thereof. The invention also relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in therapy. The invention also relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of cancer. The invention also relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of pre-cancerous syndromes. The invention also relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of beta hemoglobinopathies. The invention also relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of sickle cell disease. The invention also relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of sickle cell anemia. The invention also relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of beta thalassemia. The invention also relates to the use of a compound of Formula (I) or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of cancer. The invention also relates to the use of a compound of Formula (I) or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of pre-cancerous syndromes. The invention also relates to the use of a compound of Formula (I) or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of beta hemoglobinopathies. The invention also relates to the use of a compound of Formula (I) or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of sickle cell disease. The invention also relates to the use of a compound of Formula (I) or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of sickle cell anemia. The invention also relates to the use of a compound of Formula (I) or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment of beta thalassemia. Included in the present invention are pharmaceutical compositions that comprise a pharmaceutical carrier and a compound of Formula (I) or a pharmaceutically acceptable salt thereof. The invention also relates to a pharmaceutical composition as defined above for use in therapy. Also included in the present invention are methods of co-administering the presently invented DNMT1 inhibiting compounds with a further anti-neoplastic agent or agents. Also included in the present invention are methods of co-administering the presently invented DNMT1 inhibiting compounds with a further fetal hemoglobin inducing agent or agents. Also included in the present invention are methods of co-administering the presently invented DNMT1 inhibiting compounds with a further agent or agents that lessens the severity of beta hemoglobinopathies. Also included in the present invention are methods of co-administering the presently invented DNMT1 inhibiting compounds with a further agent or agents that lessens the severity of sickle cell anemia. Also included in the present invention are methods of co-administering the presently invented DNMT1 inhibiting compounds with a further agent or agents that lessens the severity of sickle cell disease. Also included in the present invention are methods of co-administering the presently invented DNMT1 inhibiting compounds with a further agent or agents that lessens the severity of beta thalassemia. The invention also relates to a combination for use in therapy which comprises a therapeutically effective amount of (i) a compound of Formula (I) or a pharmaceutically acceptable salt thereof; and (ii) at least one anti-neoplastic agent. The invention also relates to a combination for use in therapy which comprises a therapeutically effective amount of (i) a compound of Formula (I) or a pharmaceutically acceptable salt thereof; and (ii) at least one further fetal hemoglobin inducing agent. The invention also relates to a combination for use in therapy which comprises a therapeutically effective amount of (i) a compound of Formula (I) or a pharmaceutically acceptable salt thereof; and (ii) at least one further agent that lessens the severity of beta hemoglobinopathies. The invention also relates to a combination for use in therapy which comprises a therapeutically effective amount of (i) a compound of Formula (I) or a pharmaceutically acceptable salt thereof; and (ii) at least one further agent that lessens the severity of sickle cell anemia. The invention also relates to a combination for use in therapy which comprises a therapeutically effective amount of (i) a compound of Formula (I) or a pharmaceutically acceptable salt thereof; and (ii) at least one further agent that lessens the severity of sickle cell disease. The invention also relates to a combination for use in therapy which comprises a therapeutically effective amount of (i) a compound of Formula (I) or a pharmaceutically acceptable salt thereof; and (ii) at least one further agent that lessens the severity of beta thalassemia.

BRIEF DESCRIPTION OF THE DRAWINGS Figure– 1A depicts the effect of Compound A on erythroid progenitor cells (EPCs).

Representative results (n=3 studies each) of 5 day treatment with Compound A on fetal hemoglobin (HbF) ELISA (open circles), and cell growth assay (closed circles). Figure– 1B depicts the effect of Compound A on HBG1 and HBG2 DNA methylation.

Erythroid progenitor cells (EPCs) were treated for 3 days with vehicle (gray bars) or 5µM Compound A (black bars), genomic DNA was extracted and bisulfite sequenced for nine loci in the promoter regions of HBG1 and HBG2 that were previously described to be sites of DNMT1 cytosine methylation. Sites of methylation are labeled as positions relative to respective start sites Figure– 2A depicts the effect of Compound A on fetal hemoglobin in the transgenic mouse model. Compound A administered orally to sickle cell disease (SCD) model transgenic mice at 10 or 50 mg/kg, BID daily caused dose dependent increases in %HbF protein, measured by HPLC. Figure– 2B depicts the effect of Compound A on fetal hemoglobin in the transgenic mouse model. Compound A administered orally to SCD transgenic mice at 10 or 50 mg/kg, BID daily caused dose dependent increases in %F- reticulocytes and %F-RBCs, measured by flow cytometry. DETAILED DESCRIPTION OF THE INVENTION

This invention relates to compounds of Formula (Iar) and to the use of compounds of Formula (Iar) in the methods of the invention:

wherein:

X 1ar and X 2ar are independently selected from: hydrogen,

cyano,

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

- OC 1-6 alkyl,

- OR e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d ,

heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R d ,

-SH, and

- SR a ; Y ar is selected from: S, NH, NR z , O, S(O) and S(O)2; R 1ar is selected from: amino,

- NHR a ,

- NR b R c ,

cyano,

fluoro, chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

- OC 1-6 alkyl,

- OR e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R d , aryl,

a ryl substituted from 1 to 4 times by R d , heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d , -SH, and

- SR a ; R 2ar is selected from: hydrogen,

C 1-6 alkyl,

R e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R d , -C(O)OR a ,

- C(O)NHR a , and

- C(O)NR b R c ; R 3ar is selected from: hydrogen,

aryl,

a ryl substituted from 1 to 4 times by R d , heteroaryl, and

h eteroaryl substituted from 1 to 4 times by R d ; R 4ar is selected from: hydrogen,

C 1-6 alkyl,

R e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R d , -C(O)OR a ,

- C(O)NHR a , and

- C(O)NR b R c ; R 5ar is selected from: amino,

- NHR a ,

- NR b R c ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

- OC 1-6 alkyl,

- OR e ,

-Oaryl,

- Oaryl substituted from 1 to 4 times by R d , -Oheteroaryl,

- Oheteroaryl substituted from 1 to 4 times by R d , -SH, and

- SR a ; where: e ach R a is independently selected from

C 1-6 alkyl,

R e ,

aryl,

a ryl substituted from 1 to 4 times by R d , heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d cycloalkyl, cycloalkyl substituted from 1 to 4 times by R d ,

heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d ; R b and R c are independently selected from:

C 1-6 alkyl,

R e ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d ;

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d ,

heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d , or

R b and R c are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d , C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

–-CN,

oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 ,

- N(H)C 1-4 alkyl,

- N(H)R e , - N(C 1-4 alkyl) 2 ,

- NR e R e ,

SO 2 NH 2,

SO 2 CH 2 CH 3 , and

SO 2 CH 3 ; each R d is independently selected from: fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, aryl,

a ryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

C 1-4 alkoxy,

C 1-4 alkoxy substituted from 1 to 4 times by fluoro,

-Oaryl,

- Oaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

-C(O)H,

- C(O)R zz ,

-C(O)aryl,

- C(O)aryl substituted from 1 to 4 times by R zz ,

-C(O)heteroaryl,

- C(O)heteroaryl substituted from 1 to 4 times by R zz , -OC(O)H,

- CO(O)R zz ,

-OC(O)aryl,

- CO(O)aryl substituted from 1 to 4 times by R zz ,

-OC(O)heteroaryl,

- OC(O)heteroaryl substituted from 1 to 4 times by R zz , mercapto,

- SR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

-S(O)H,

- S(O)R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- S(O) 2 H,

- S(O)2R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- S(O) 2 NH 2 ,

- S(O)2NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- S(O)2NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

- NHS(O) 2 H,

- NHS(O)2R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

-NHC(O)H,

- NHC(O)R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- C(O)NH 2 ,

- C(O)NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- C(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

-C(O)OH,

- C(O)OR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, oxo,

hydroxy,

amino,

- NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

nitro,

cyano,

- NHC(O)NH 2 , -NHC(O)NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, - NHC(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

e ach R e is independently selected from:

C 1-6 alkyl substituted with from 1 to 9 substitutents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C1-6alkyl,

- OC 1-6 alkyl,

- OC 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

mercapto,

- SR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

-S(O)H,

- S(O)R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O) 2 H, -S(O)2R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

oxo,

hydroxy,

amino,

- NHR xx ,

w here R xx is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl,

a nd C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, o xo, -ORxy, -COOH,–-CN, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and –NR xy R xz , where R xy and R xz are independently s elected from: hydrogen, aryl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, - OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH,

- NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 Substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

guanidino,

-C(O)OH,

- C(O)OR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- C(O)NH 2 ,

- C(O)NHR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- C(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 Substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

aryl,

a ryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

-Oaryl,

- Oaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

-Oheteroaryl,

- Oheteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O) 2 NH 2 ,

- S(O)2NHR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–-CN,

- S(O)2NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 Substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- NHS(O) 2 H,

- NHS(O)2R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN, -NHC(O)NHR xp ,

w here R xp is selected from heteroaryl, c ycloalkyl, heterocyloalkyl, and C 1-6 alkyl substituted with from 1 to 4 substituents independently selected from: -COOH, -NH 2 , and –-CN,

- NHC(O)NR x3 R x4 ,

w here R x3 and R x4 are each independently selected from heteroaryl, cycloalkyl, heterocyloalkyl, a nd C 1-6 alkyl substituted with from 1 to 6

Substituents independently selected from:

- COOH, -NH 2 , and–-CN,

nitro, and

cyano; each R f is independently C1-6alkyl optionally substituted from 1 to 6 times by R e ; each R g is independently aryl optionally substituted from 1 to 5 times by R x ,

w here R x is independently selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, each R h is independently heteroaryl optionally substituted from 1 to 5 times by R x ,

w here R x is independently selected from aryl, h eteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN, and R z is selected from

C 1-6 alkyl,

R e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d ; R zz is selected from

C 1-6 alkyl, and

R e ; provided that:

at least one of R 2ar , R 3ar and R 4ar , is hydrogen,

R 2ar , R 3ar and R 4ar are not all hydrogen, and

X 1ar and X 2ar are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof. Suitably in the compounds of Formula (Iar) R 2ar is -C(O)NH 2 . Suitably in the compounds of Formula (Iar) R 3ar is aryl optionally substituted from 1 to 4 times by R d .

Included in the compounds of the invention and used in the methods of the invention are compounds of Formula (I):

(I)

wherein:

X 1 and X 2 are independently selected from: hydrogen,

cyano,

fluoro,

chloro,

bromo, iodo,

C 1-6 alkyl,

R e ,

- OC 1-6 alkyl,

- OR e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R d , -SH, and

- SR a ; Y is selected from: S, NH, NR z , O, S(O) and S(O)2; R 1 is selected from: amino,

- NHR a ,

- NR b R c ,

cyano,

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

- OC 1-6 alkyl,

- OR e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R d , -SH, and

- SR a ; R 2 is selected from: hydrogen, C 1-6 alkyl,

R e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R d , -C(O)OR a ,

- C(O)NHR a , and

- C(O)NR b R c ; R 3 is selected from: hydrogen,

aryl,

a ryl substituted from 1 to 4 times by R d , heteroaryl, and

h eteroaryl substituted from 1 to 4 times by R d ; R 4 is selected from: hydrogen,

C1-6alkyl,

R e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R d , -C(O)OR a ,

- C(O)NHR a , and

- C(O)NR b R c ; R 5 is selected from: amino,

- NHR a ,

- NR b R c ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

- OC 1-6 alkyl, -OR e ,

-Oaryl,

- Oaryl substituted from 1 to 4 times by R d ,

-Oheteroaryl,

- Oheteroaryl substituted from 1 to 4 times by R d ,

-SH, and

- SR a ; where: e ach R a is independently selected from

C 1-6 alkyl,

R e ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d ,

heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d ; R b and R c are independently selected from:

C 1-6 alkyl,

R e ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d ;

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d ,

heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d , or

R b and R c are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro, chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

aryl,

a ryl substituted from 1 to 4 times by R d , cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d , C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN, –-CN,

oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 ,

- N(H)C 1-4 alkyl,

- N(H)R e ,

- N(C 1-4 alkyl) 2 ,

- NR e R e ,

SO 2 NH 2,

SO 2 CH 2 CH 3 , and

SO 2 CH 3 ; each R d is independently selected from: fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–-CN, aryl,

a ryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

C 1-4 alkoxy,

C 1-4 alkoxy substituted from 1 to 4 times by fluoro,

-Oaryl,

- Oaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

-C(O)H,

- C(O)R zz ,

-C(O)aryl,

- C(O)aryl substituted from 1 to 4 times by R zz ,

-C(O)heteroaryl,

- C(O)heteroaryl substituted from 1 to 4 times by R zz , -OC(O)H,

- CO(O)R zz ,

-OC(O)aryl,

- CO(O)aryl substituted from 1 to 4 times by R zz ,

-OC(O)heteroaryl,

- OC(O)heteroaryl substituted from 1 to 4 times by R zz , mercapto,

- SR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–-CN,

-S(O)H,

- S(O)R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- S(O) 2 H,

- S(O)2R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- S(O) 2 NH 2 ,

- S(O)2NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, -S(O)2NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

- NHS(O) 2 H,

- NHS(O)2R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–-CN,

-NHC(O)H,

- NHC(O)R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- C(O)NH 2 ,

- C(O)NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- C(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

-C(O)OH,

- C(O)OR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, oxo, hydroxy,

amino,

- NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, - NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

nitro,

cyano,

- NHC(O)NH 2 ,

- NHC(O)NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, - NHC(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

e ach R e is independently selected from:

C 1-6 alkyl substituted with from 1 to 9 substitutents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

- OC 1-6 alkyl,

- OC 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

mercapto,

- SR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

-S(O)H,

- S(O)R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O) 2 H,

- S(O)2R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

oxo,

hydroxy,

amino,

- NHR xx ,

w here R xx is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl,

a nd C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, o xo, -ORxy, -COOH,–-CN, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and –NR xy R xz , where R xy and R xz are independently s elected from: hydrogen, aryl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH,

- NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 Substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

guanidino,

-C(O)OH,

- C(O)OR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- C(O)NH 2 ,

- C(O)NHR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- C(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 Substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

aryl,

a ryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

-Oaryl, -Oaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

-Oheteroaryl,

- Oheteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R x , where R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O) 2 NH 2 ,

- S(O)2NHR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O)2NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 Substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- NHS(O) 2 H,

- NHS(O)2R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- NHC(O)NHR xp ,

w here R xp is selected from heteroaryl, c ycloalkyl, heterocyloalkyl, and C 1-6 alkyl substituted with from 1 to 4 substituents independently selected from: -COOH, -NH 2 , and –-CN,

- NHC(O)NR x3 R x4 ,

w here R x3 and R x4 are each independently selected from heteroaryl, cycloalkyl, heterocyloalkyl, a nd C 1-6 alkyl substituted with from 1 to 6

Substituents independently selected from:

- COOH, -NH 2 , and–-CN,

nitro, and

cyano; each R f is independently C 1-6 alkyl optionally substituted from 1 to 6 times b y R e ; each R g is independently aryl optionally substituted from 1 to 5 times by R x ,

w here R x is independently selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, e ach R h is independently heteroaryl optionally substituted from 1 to 5 times by R x ,

w here R x is independently selected from aryl, h eteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN, and R z is selected from

C 1-6 alkyl,

R e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d ; R zz is selected from

C 1-6 alkyl, and

R e ; provided that:

at least one of R 2 , R 3 and R 4 , is hydrogen,

R 2 , R 3 and R 4 are not all hydrogen, and

X 1 and X 2 are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof. Included in the compounds of the invention and used in the methods of the invention are compounds of Formula (II):

wherein: X 21 and X 22 are independently selected from: hydrogen,

cyano,

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

- OC 1-6 alkyl,

- OR e ,

cycloalkyl,

heterocycloalkyl, and

-SH; Y 1 is selected from: S, NH, NR z , S(O) and S(O)2; R 21 is selected from: amino,

cyano,

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

- OC 1-6 alkyl,

- OR e ,

- NHR a ,

- NR b R c ,

cycloalkyl,

c ycloalkyl substituted with from 1 to 4 times by R d , heterocycloalkyl,

-SH, and

- SR a ; R 22 is selected from: hydrogen,

C 1-6 alkyl,

R e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R d , -C(O)OR a , and

- C(O)NHR a ; R 23 is selected from: hydrogen,

aryl,

a ryl substituted from 1 to 4 times by R d , heteroaryl, and

h eteroaryl substituted from 1 to 4 times by R d ; R 24 is selected from: hydrogen,

C 1-6 alkyl,

R e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R d , -C(O)OR a , and

- C(O)NHR a ; R 25 is selected from: amino,

- NHR a ,

- NR b R c ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

- OC 1-6 alkyl,

- OR e , -Oaryl,

-Oheteroaryl,

-SH, and

- SR a ; where: e ach R a is independently selected from

C 1-6 alkyl,

R e ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d ,

heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d ; R b and R c are independently selected from:

C 1-6 alkyl,

R e ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d ;

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d ,

heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d , or

R b and R c are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo, C 1-6 alkyl,

R e ,

aryl,

a ryl substituted from 1 to 4 times by R d , cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d , C 1-4 alkoxy, C 1-4 alkoxy substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN, –-CN,

oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 ,

- N(H)C 1-4 alkyl,

- N(H)R e , - N(C 1-4 alkyl) 2 ,

SO 2 NH 2,

SO 2 CH 2 CH 3 , and

SO 2 CH 3 ; each R d is independently selected from: fluoro,

chloro,

bromo,

iodo, C 1-6 alkyl,

R e ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, aryl,

a ryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

C 1-4 alkoxy,

C 1-4 alkoxy substituted from 1 to 4 times by fluoro,

-Oaryl,

- Oaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

-C(O)H,

- C(O)R zz ,

-C(O)aryl, -C(O)aryl substituted from 1 to 4 times by R zz ,

-C(O)heteroaryl,

- C(O)heteroaryl substituted from 1 to 4 times by R zz ,

-OC(O)H,

- CO(O)R zz ,

-OC(O)aryl,

- CO(O)aryl substituted from 1 to 4 times by R zz ,

-OC(O)heteroaryl,

- OC(O)heteroaryl substituted from 1 to 4 times by R zz , mercapto,

- SR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

-S(O)H,

- S(O)R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- S(O) 2 H,

- S(O)2R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- S(O) 2 NH 2 ,

- S(O)2NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- S(O)2NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

- NHS(O) 2 H,

- NHS(O)2R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

-NHC(O)H,

- NHC(O)R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- C(O)NH 2 ,

- C(O)NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- C(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

-C(O)OH,

- C(O)OR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, oxo,

hydroxy,

amino,

- NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, - NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

nitro,

cyano,

- NHC(O)NH 2 ,

- NHC(O)NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, - NHC(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

e ach R e is independently selected from:

C 1-6 alkyl substituted with from 1 to 9 substitutents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

- OC 1-6 alkyl,

- OC 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN, mercapto,

- SR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

-S(O)H,

- S(O)R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O) 2 H,

- S(O)2R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

oxo,

hydroxy,

amino,

- NHR xx ,

w here R xx is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl,

and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, o xo, -ORxy, -COOH,–-CN, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and –NR xy R xz , where R xy and R xz are independently s elected from: hydrogen, aryl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, - OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH,

- NR x1 R x2 , where R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 Substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

guanidino,

-C(O)OH,

- C(O)OR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- C(O)NH 2 ,

- C(O)NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- C(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 Substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

aryl,

a ryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

-Oaryl,

- Oaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

-Oheteroaryl,

- Oheteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R x , where R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O) 2 NH 2 ,

- S(O)2NHR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O)2NR x1 R x2 , where R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 Substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- NHS(O) 2 H,

- NHS(O)2R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- NHC(O)NHR xp ,

w here R xp is selected from heteroaryl, c ycloalkyl, heterocyloalkyl, and C 1-6 alkyl substituted with from 1 to 4 substituents independently selected from: -COOH, -NH 2 , and –-CN,

- NHC(O)NR x3 R x4 ,

w here R x3 and R x4 are each independently selected from heteroaryl, cycloalkyl, heterocyloalkyl, a nd C 1-6 alkyl substituted with from 1 to 6

Substituents independently selected from:

- COOH, -NH 2 , and–-CN,

nitro, and

cyano; each R f is independently C 1-6 alkyl optionally substituted from 1 to 6 times b y R e ; each R g is independently aryl optionally substituted from 1 to 5 times by R x ,

w here R x is independently selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, each R h is independently heteroaryl optionally substituted from 1 to 5 times by R x ,

w here R x is independently selected from aryl, h eteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents Independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN, and R z is selected from

C 1-6 alkyl,

R e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d ; R zz is selected from

C 1-6 alkyl, and

R e ; provided that:

at least one of R 22 , 23 24 ogen,

R 22 , R 23 and R 24 ar , nd

X 21 and X 22 are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof. Included in the compounds of the invention and used in the methods of the invention are compounds of Formula (III): X 31

R 35

wherein:

X 31 and X 32 are independently selected from: hydrogen,

cyano, fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

- OC 1-6 alkyl,

cycloalkyl, and

-SH; Y 2 is selected from: S, NH, NR z and S(O); R 31 is selected from: C 1-6 alkyl,

R e1 ,

- OC 1-6 alkyl,

- OR e1 ,

- NHR a1 ,

- NR b1 R c1 ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d1 , -SH, and

- SR a1 ; R 32 is selected from: hydrogen,

C 1-6 alkyl,

R e1 ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d1 , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d1 ; R 33 is selected from: hydrogen,

aryl,

a ryl substituted from 1 to 4 times by R d1 , heteroaryl, and

h eteroaryl substituted from 1 to 4 times by R d1 ; R 34 is selected from: hydrogen,

C 1-6 alkyl,

R e1 ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d1 , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d1 ; R 35 is selected from: amino,

- NHR a1 ,

- NR b1 R c1 ,

aryl,

a ryl substituted from 1 to 4 times by R d1 ,

- OC 1-6 alkyl,

- OR e1 ,

-SH, and

- SR a1 ; where: e ach R a1 is independently selected from

C 1-6 alkyl,

R e1 ,

aryl,

heteroaryl,

cycloalkyl, and

heterocycloalkyl; R b1 and R c1 are independently selected from:

C 1-6 alkyl,

R e1 ,

aryl,

a ryl substituted from 1 to 4 times by R d1 , heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d1 ;

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d1 ,

heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d1 , or R b1 and R c1 are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e1 ,

aryl,

a ryl substituted from 1 to 4 times by R d1 ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d1 , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d1 , C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

–-CN,

oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 ,

- N(H)C 1-4 alkyl, -N(H)R e1 ,

- N(C 1-4 alkyl) 2 ,

SO 2 NH 2,

SO 2 CH 2 CH 3 , and

SO 2 CH 3 ; each R d1 is independently selected from: fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e1 ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

aryl,

a ryl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

C 1-4 alkoxy,

C 1-4 alkoxy substituted from 1 to 4 times by fluoro, -Oaryl,

-C(O)H,

- C(O)R zz ,

-C(O)aryl,

-C(O)heteroaryl,

-OC(O)H,

- CO(O)R zz ,

-OC(O)aryl,

-OC(O)heteroaryl,

mercapto,

- SR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

-S(O)H,

- S(O)R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- S(O) 2 H,

- S(O)2R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- S(O) 2 NH 2 ,

- S(O)2NHR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- NHS(O) 2 H,

- NHS(O)2R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

-NHC(O)H,

- NHC(O)R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- C(O)NH 2 ,

- C(O)NHR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

-C(O)OH,

- C(O)OR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

oxo,

hydroxy,

amino,

- NHR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

nitro,

cyano,

- NHC(O)NH 2 , and

- NHC(O)NHR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro; each R e1 is independently selected from:

C 1-6 alkyl substituted with from 1 to 9 substitutents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

- OC 1-6 alkyl,

- OC 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN, mercapto,

- SR xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

-S(O)H,

- S(O)R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- S(O) 2 H,

- S(O)2R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro, oxo,

hydroxy,

amino,

- NHR xx ,

w here R xx is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl,

a nd C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, o xo, -ORxy, -COOH,–-CN, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and –NR xy R xz , where R xy and R xz are independently s elected from: hydrogen, aryl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, - OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH,

- NR x1x R x2x ,

w here R x1x and R x2x are each independently s elected from C 1-4 alkyl, and C 1-4 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, and–OH,

guanidino,

-C(O)OH,

- C(O)OR xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- C(O)NHR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, and heterocyloalkyl,

aryl,

a ryl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

-Oaryl,

- Oaryl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro, heteroaryl,

h eteroaryl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

-Oheteroaryl,

- Oheteroaryl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro, cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

heterocycloalkyl, heterocycloalkyl substituted from 1 to 4 times by R x , where R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O) 2 NH 2 ,

- S(O)2NHR xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- NHS(O) 2 H,

- NHS(O)2R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- NHC(O)NHR xa ,

w here R xa is selected from heteroaryl, cycloalkyl, and heterocyloalkyl, nitro, and

cyano; each R f is independently C 1-6 alkyl optionally substituted from 1 to 6 times b y R e1 ; each R g is independently aryl optionally substituted from 1 to 5 times by R x ,

w here R x is independently selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, each R h is independently heteroaryl optionally substituted from 1 to 5 times by R x ,

w here R x is independently selected from aryl, h eteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents Independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN, and R z is selected from

C 1-6 alkyl,

R e1 ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d1 , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d1 ; R zz is selected from

C 1-6 alkyl, and

R e1 ; provided that:

at least one of R 32 , R 33 and R 34 , is hydrogen,

R 32 , R 33 and R 34 are not all hydrogen, and

X 31 and X 32 are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof. Suitably in the compounds of Formula (III), neither X 31 nor X 32 are hydrogen. Included in the compounds of the invention and used in the methods of the invention are compounds of Formula (IVar):

wherein: X 41ar and X 42ar are independently selected from: --CN, fluoro, chloro, bromo and iodo;

Y 4ar is selected from: S and NH; R 41ar is selected from: C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, C1-4alkyloxy, -OH, -COOH, -NH2 - N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 and–-CN, C 1-4 alkyloxy,

C 1-4 alkyloxy substituted from 1 to 4 times by fluoro,

- N(H)C 1-4 alkyl,

- N(C 1-4 alkyl) 2 ,

- SC 1-4 alkyl,

aryl,

aryl substituted with from 1 to 4 substituents

independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN, C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-NO 2 , and

-NH 2 , heteroaryl,

heteroaryl substituted with from 1 to 4 substituents

independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN,

C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-NO 2 , and

-NH 2 ,

cycloalkyl,

cycloalkyl substituted with from 1 to 4 substituents

independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN,

C 1-4 alkoxy,

–-CN,

oxo, -OH,

-NO 2 , and

-NH 2 ;

R 42ar is selected from:

hydrogen,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, i odo, oxo, -OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and–-CN, heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN,

-NHC(O)H,

- NHC(O)R xa1 ,

w here R xa1 is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-NO 2 , and

-NH 2 ; R 43ar is selected from:

hydrogen,

C 1-6 alkyl,

aryl,

aryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C1-6alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 49 and–NR 46 R 47 ,

where R 46 and R 47 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 48 R 49 , where R 48 and R 49 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, C 1-4 alkoxy,

–-CN, oxo,

-OH,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 ,

-NO 2 , and

-NH2,

heteroaryl, and

heteroaryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 49 and–NR 46 R 47 ,

where R 46 and R 47 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 48 R 49 , where R 48 and R 49 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 ,

-NO 2 , and

-NH 2 ; and

R 44ar and R 45ar are independently selected from:

hydrogen, C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, i odo, heterocycloalkyl, C 1-4 alkoxy, oxo, -OH, -NH 2 and–-CN, heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN,

aryl,

C 1-4 alkoxy,

–-CN, oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 , and

SO 2 NH 2, or

R 44ar and R 45ar are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected

from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, i odo, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, - OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and –-CN,

aryl,

cycloalkyl,

heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents i ndependently selected from: C 1-6 alkyl,

- C 1-6 alkylOH, fluoro, -C 1-6 alkylNH 2 ,

chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN, C 1-4 alkoxy, C 1-4 alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

–-CN,

oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 ,

- N(H)C 1-4 alkyl,

- N(H)C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, bromo, i odo, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl,

- OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and –-CN,

- N(C 1-4 alkyl) 2 ,

SO 2 NH 2,

SO 2 CH 2 CH 3 , and

SO 2 CH 3 ;

provided that:

R 42ar and R 43ar are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (IVar) neither R 44ar nor R 45ar is hydrogen. Suitably in the compounds of Formula (IVar) R 42ar is -C(O)NH 2 . Suitably in the compounds of Formula (IVar) R 43ar is aryl substituted with from 1 to 4 substituents independently selected from: fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 49 and–NR 46 R 47 ,

where R 46 and R 47 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 48 R 49 , where R 48 and R 49 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH.

Included in the compounds of the invention and used in the methods of the invention are compounds of Formula (IV):

wherein: X 41 and X 42 are independently selected from: --CN, fluoro, chloro, bromo and iodo; Y 4 is selected from: S and NH; R 41 is selected from: C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo,

i odo, oxo, C 1-4 alkyloxy, -OH, -COOH, -NH 2 - N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 and–-CN,

C 1-4 alkyloxy,

C 1-4 alkyloxy substituted from 1 to 4 times by fluoro,

- N(H)C 1-4 alkyl,

- N(C 1-4 alkyl) 2 , -SC 1-4 alkyl,

cycloalkyl,

cycloalkyl substituted with from 1 to 4 substituents

independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN,

C 1-4 alkoxy,

–-CN, oxo,

-OH,

-NO 2 , and

-NH 2 ;

R 42 is selected from:

hydrogen,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH2, -N(H)C1-4alkyl, -N(C1-4alkyl)2, and–-CN, heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH2 and–-CN,

-NHC(O)H,

- NHC(O)R xa1 ,

w here R xa1 is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-NO 2 , and -NH 2 ;

R 43 is selected from:

hydrogen,

C 1-6 alkyl,

aryl,

aryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 49 and–NR 46 R 47 ,

where R 46 and R 47 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 48 R 49 , where R 48 and R 49 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 ,

-NO 2 , and

-NH 2 ,

heteroaryl, and

heteroaryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 49 and–NR 46 R 47 ,

where R 46 and R 47 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 48 R 49 , where R 48 and R 49 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 ,

-NO 2 , and

-NH 2 ; and

R 44 and R 45 are independently selected from:

hydrogen, C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, i odo, heterocycloalkyl, C 1-4 alkoxy, oxo, -OH, -NH 2 and–-CN, heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN,

aryl, C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 , and

SO 2 NH 2, or

R 44 and R 45 are taken together with the nitrogen to which they are

attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected

from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, i odo, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, - OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and –-CN,

aryl,

cycloalkyl,

heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents i ndependently selected from: C 1-6 alkyl,

- C 1-6 alkylOH, fluoro, -C 1-6 alkylNH 2 , chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN, C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

–-CN,

oxo,

-OH,

-COOH,

-NO2,

-NH 2 ,

- N(H)C 1-4 alkyl,

- N(H)C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, bromo, iodo, C1-4alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, - OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and –-CN,

- N(C 1-4 alkyl) 2 ,

SO 2 NH 2,

SO 2 CH 2 CH 3 , and

SO 2 CH 3 ;

provided that:

R 42 and R 43 are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (IV) neither R 44 nor R 45 is hydrogen. This invention relates to novel compounds of Formula (IVaar) and to the use of compounds of Formula (IVaar) in the methods of the invention:

wherein:

X 41aar and X 42aar are independently selected from: --CN, fluoro, chloro, bromo and iodo; Y 4aar is selected from: S and NH; R 41aar is selected from: C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo,

i odo, oxo, C 1-4 alkyloxy, -OH, -COOH, -NH 2 - N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 and–-CN,

C 1-4 alkyloxy,

C 1-4 alkyloxy substituted from 1 to 4 times by fluoro,

- N(H)C 1-4 alkyl,

- N(C 1-4 alkyl) 2 ,

- SC 1-4 alkyl,

aryl,

aryl substituted with from 1 to 4 substituents

independently selected from:

fluoro,

chloro, bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN,

C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-NO 2 , and

-NH 2 ,

heteroaryl,

heteroaryl substituted with from 1 to 4 substituents

independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN,

C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-NO 2 , and

-NH 2 ,

cycloalkyl, cycloalkyl substituted with from 1 to 4 substituents

independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN, C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-NO 2 , and

-NH2;

R 42aar is selected from:

hydrogen,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, i odo, oxo, -OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and–-CN, heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN,

-NHC(O)H,

- NHC(O)R xa1 ,

w here R xa1 is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-NO 2 , and

-NH 2 ;

R 43aar is selected from:

hydrogen,

C 1-6 alkyl,

aryl,

aryl substituted with from 1 to 4 substituents independently selected

from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 49 and–NR 46 R 47 ,

where R 46 and R 47 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 48 R 49 , where R 48 and R 49 are independently selected from: hydrogen, phenyl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 ,

-NO 2 , and

-NH 2 ,

heteroaryl, and

heteroaryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 49 and–NR 46 R 47 , where R 46 and R 47 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 48 R 49 , where R 48 and R 49 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 ,

-NO 2 , and

-NH 2 ; and

R 44aar and R 45aar are independently selected from:

hydrogen, C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, heterocycloalkyl, C 1-4 alkoxy, oxo, -OH, -NH 2 and–-CN, heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN, aryl,

C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

–-CN,

oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 , and

SO 2 NH 2, or

R 44aar and R 45aar are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo, iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, i odo, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, - OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and –-CN,

aryl,

cycloalkyl,

heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents i ndependently selected from: C 1-6 alkyl,

- C 1-6 alkylOH, fluoro, -C 1-6 alkylNH 2 ,

chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN, C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 ,

-N(H)C1-4alkyl, -N(H)C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, bromo, i odo, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, - OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and –-CN, -N(C 1-4 alkyl) 2 ,

SO 2 NH 2,

SO 2 CH 2 CH 3 , and

SO 2 CH 3 ;

provided that:

R 42aar and R 43aar are not both hydrogen, and

R 44aar and R 45aar are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (IVaar) neither R 44aar nor R 45aar is hydrogen. Suitably in the compounds of Formula (IVaar) R 42aar is -C(O)NH 2 . Suitably in the compounds of Formula (IVaar) R 43aar is aryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 49 and–NR 46 R 47 ,

where R 46 and R 47 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 48 R 49 , where R 48 and R 49 are independently selected from:

h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH.

This invention relates to novel compounds of Formula (IVa) and to the use of compounds of Formula (IVa) in the methods of the invention:

wherein: X 41a and X 42a are independently selected from: --CN, fluoro, chloro, bromo and iodo; Y 4a is selected from: S and NH; R 41a is selected from: C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo,

i odo, oxo, C 1-4 alkyloxy, -OH, -COOH, -NH 2 - N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 and–-CN,

C 1-4 alkyloxy, C 1-4 alkyloxy substituted from 1 to 4 times by fluoro, -N(H)C 1-4 alkyl,

- N(C 1-4 alkyl) 2 , -SC 1-4 alkyl,

cycloalkyl,

cycloalkyl substituted with from 1 to 4 substituents

independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN, C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-NO 2 , and

-NH 2 ;

R 42a is selected from:

hydrogen,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, i odo, oxo, -OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and–-CN, heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 4 substituents independently selected from: fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN,

-NHC(O)H,

- NHC(O)R xa1 ,

w here R xa1 is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

C1-4alkoxy,

–-CN,

oxo,

-OH,

-NO 2 , and

-NH 2 ;

R 43a is selected from:

hydrogen,

C 1-6 alkyl,

aryl,

aryl substituted with from 1 to 4 substituents independently selected

from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 49 and–NR 46 R 47 ,

where R 46 and R 47 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 48 R 49 , where R 48 and R 49 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 ,

-NO2, and

-NH 2 ,

heteroaryl, and

heteroaryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

bromo, iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 49 and–NR 46 R 47 ,

where R 46 and R 47 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 48 R 49 , where R 48 and R 49 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 ,

-NO 2 , and

-NH 2 ; and

R 44a and R 45a are independently selected from:

hydrogen, C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, i odo, heterocycloalkyl, C 1-4 alkoxy, oxo, -OH, -NH 2 and–-CN, heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN, aryl,

C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

–-CN,

oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 , and

SO 2 NH 2, or

R 44a and R 45a are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, i odo, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, - OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and –-CN,

aryl,

cycloalkyl,

heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents i ndependently selected from: C 1-6 alkyl,

- C 1-6 alkylOH, fluoro, -C 1-6 alkylNH 2 , chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN, C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 ,

- N(H)C 1-4 alkyl,

- N(H)C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, bromo, i odo, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl,

- OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and –-CN,

- N(C 1-4 alkyl) 2 ,

SO 2 NH 2,

SO 2 CH 2 CH 3 , and

SO 2 CH 3 ;

provided that:

R 42a and R 43a are not both hydrogen, and

R 44a and R 45a are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (IVa) neither R 44a nor R 45a is hydrogen.

Included in the compounds of the invention and used in the methods of the invention are compounds of Formula (V):

wherein:

X 51 and X 52 are independently selected from: --CN, fluoro and chloro; Y 5 is selected from: S and NH; R 50 is selected from: C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro, - N(H)C 1-4 alkyl,

- N(C 1-4 alkyl) 2 ,

- SC 1-4 alkyl,

C 1-4 alkyloxy,

cycloalkyl,

cycloalkyl substituted with from 1 to 5 substituents

independently selected from:

fluoro,

chloro,

-OH,

C 1-6 alkyl, and

C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro and chloro;

R 51 is selected from:

hydrogen,

C 1-6 alkyl,

- C(O)NHR55, where R55 is selected from: hydrogen, C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro and chloro,

heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, chloro, bromo, oxo, -OH, -NH 2 and–-CN,

-NHC(O)H,

- NHC(O)R xa2 ,

w here R xa2 is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

C 1-4 alkoxy,

–-CN,

oxo,

-OH, and

-NH 2 ;

R 52 is selected from:

hydrogen,

C 1-6 alkyl,

aryl,

aryl substituted with from 1 to 4 substituents independently selected

from:

fluoro,

chloro,

C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 59 and–NR 56 R 57 ,

where R 56 and R 57 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 58 R 59 , where R 58 and R 59 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, oxo,

--CN,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 ,

-OH;

heteroaryl, and

heteroaryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C1-6alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 59 and–NR 56 R 57 ,

where R 56 and R 57 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl, - OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 58 R 59 , where R 58 and R 59 are independently selected from: hydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, oxo,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 ,

-OH; and

R 53 and R 54 are independently selected from:

hydrogen,

C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 6 substituents

independently selected from: fluoro, chloro, oxo, h eterocycloalkyl, C 1-4 alkoxy, -OH and -NH 2 ,

heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro, C 1-4 alkoxy, and

-OH, or

R 53 and R 54 are taken together with the nitrogen to which they are

attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro, chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, - OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and –-CN,

heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents i ndependently selected from: C 1-6 alkyl, -C 1-6 alkylOH, fluoro, -C 1-6 alkylNH 2 , chloro, oxo and -OH,

C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

–-CN,

oxo,

-OH,

-COOH,

-NH 2,

- N(H)C 1-4 alkyl,

- N(H)C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, - OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and –-CN, and -N(C 1-4 alkyl) 2;

provided that:

R 51 and R 52 are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (V) neither R 53 nor R 54 is hydrogen.

This invention relates to novel compounds of Formula (Vaar) and to the use of compounds of Formula (Vaar) in the methods of the invention:

wherein:

X 51aar and X 52aar are independently selected from: --CN, fluoro and chloro; Y 5aar is selected from: S and NH; R 50aar is selected from: C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro, - N(H)C 1-4 alkyl,

- N(C 1-4 alkyl) 2 ,

- SC 1-4 alkyl,

C1-4alkyloxy, aryl,

alkyl substituted with from one to five substituents

independently selected from:

fluoro,

chloro,

-OH,

C 1-6 alkyl, and

C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro and chloro, heteroaryl,

heteroalkyl substituted with from one to five substituents independently selected from:

fluoro,

chloro,

-OH,

C 1-6 alkyl, and

C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro and chloro, cycloalkyl,

cycloalkyl substituted with from one to five substituents

independently selected from:

fluoro,

chloro,

-OH,

C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro and chloro; R 51aar is selected from:

hydrogen,

C1-6alkyl, -C(O)NHR55, where R55 is selected from: hydrogen, C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro and chloro,

heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 6 substituents

independently selected from: fluoro, chloro, bromo, oxo, -OH, -NH 2 and–-CN,

-NHC(O)H,

- NHC(O)R xa2 ,

w here R xa2 is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

C 1-4 alkoxy,

–-CN,

oxo,

-OH, and

-NH 2 ;

R 52aar is selected from:

hydrogen,

C 1-6 alkyl,

aryl,

aryl substituted with from 1 to 4 substituents independently selected

from:

fluoro,

chloro,

C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 59 and–NR 56 R 57 ,

where R 56 and R 57 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 58 R 59 , where R 58 and R 59 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, oxo,

--CN,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 ,

-OH,

heteroaryl, and

heteroaryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 59 and–NR 56 R 57 ,

where R 56 and R 57 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 58 R 59 , where R 58 and R 59 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, oxo,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 ,

-OH; and

R 53aar and R 54aar are independently selected from:

hydrogen,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 6 substituents

independently selected from: fluoro, chloro, oxo, h eterocycloalkyl, C 1-4 alkoxy, -OH and -NH 2 ,

heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro, C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro, C 1-4 alkoxy, and

-OH, or

R 53aar and R 54aar are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl,

heterocycloalkyl, methylheterocycloalkyl, -OH, -NH2, -N(H)C1-4alkyl, -N(C1-4alkyl)2, and –-CN,

heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents i ndependently selected from: C 1-6 alkyl, -C 1-6 alkylOH, fluoro, -C 1-6 alkylNH 2 , chloro, oxo and -OH,

C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

–-CN,

oxo, -OH,

-COOH,

-NH 2 ,

- N(H)C 1-4 alkyl,

- N(H)C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl,

heterocycloalkyl, methylheterocycloalkyl,

- OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and –-CN, and

- N(C 1-4 alkyl) 2;

provided that:

R 51aar and R 52aar are not both hydrogen, and

R 53aar and R 54aar are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (Vaar) neither R 53aar nor R 54aar is hydrogen. Suitably in the compounds of Formula (Vaar) R 51aar is -C(O)NH 2 . Suitably in the compounds of Formula (Vaar) R 52aar is aryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 59 and–NR 56 R 57 ,

where R 56 and R 57 are independently selected from: hydrogen, -S(O) 2 CH 3 ,

C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 58 R 59 , where R 58 and R 59 are independently selected from: hydrogen, phenyl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH.

This invention relates to novel compounds of Formula (Va) and to the use of compounds of Formula (Va) in the methods of the invention:

wherein: X 51a and X 52a are independently selected from: --CN, fluoro and chloro; Y 5a is selected from: S and NH; R 50a is selected from: C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro and chloro,

- N(H)C 1-4 alkyl,

- N(C 1-4 alkyl) 2 ,

- SC 1-4 alkyl,

C 1-4 alkyloxy,

cycloalkyl,

cycloalkyl substituted with from one to five substituents

independently selected from:

fluoro,

chloro,

-OH,

C 1-6 alkyl, and

C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro and chloro;

R 51a is selected from:

hydrogen,

C 1-6 alkyl,

- C(O)NHR55, where R55 is selected from: hydrogen, C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro and chloro,

heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 6 substituents

independently selected from: fluoro, chloro, bromo, oxo, -OH, -NH 2 and–-CN, -NHC(O)H,

- NHC(O)R xa2 ,

w here R xa2 is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

C 1-4 alkoxy,

–-CN,

oxo,

-OH, and

-NH2;

R 52a is selected from:

hydrogen,

C 1-6 alkyl,

aryl,

aryl substituted with from 1 to 4 substituents independently selected

from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 59 and–NR 56 R 57 ,

where R 56 and R 57 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 58 R 59 , where R 58 and R 59 are independently selected from: hydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, oxo,

--CN,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 ,

-OH,

heteroaryl, and

heteroaryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 59 and–NR 56 R 57 ,

where R 56 and R 57 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 58 R 59 , where R 58 and R 59 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, oxo,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 ,

-OH; and

R 53a and R 54a are independently selected from:

hydrogen,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 6 substituents

independently selected from: fluoro, chloro, oxo, h eterocycloalkyl, C 1-4 alkoxy, -OH and -NH 2 ,

heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro, C 1-4 alkoxy, and

-OH, or

R 53a and R 54a are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, - OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and –-CN,

heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents independently selected from: C1-6alkyl, - C 1-6 alkylOH, fluoro, -C 1-6 alkylNH 2 , chloro, oxo and -OH,

C 1-4 alkoxy, C 1-4 alkoxy substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

–-CN,

oxo,

-OH,

-COOH,

-NH 2 ,

- N(H)C 1-4 alkyl,

- N(H)C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, - OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and –-CN, and

- N(C 1-4 alkyl) 2;

provided that: R 51a and R 52a are not both hydrogen, and

R 53a and R 54a are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (Va) neither R 53a nor R 54a is hydrogen.

Included in the compounds of the invention and used in the methods of the invention are compounds of Formula (VI):

wherein:

Y 6 is selected from: S and NH; R 60 is selected from: C 1-3 alkyl, C 1-3 alkyl substituted with from 1 to 6 substituents

independently selected from: fluoro and chloro, - N(H)C 1-3 alkyl,

- N(C 1-3 alkyl) 2 ,

-SC1-4alkyl, C1-3alkyloxy,

cycloalkyl,

cycloalkyl substituted with from one to 3 substituents independently selected from:

fluoro,

chloro,

-OH, and

C 1-3 alkyl;

R 61 is selected from:

hydrogen,

- C(O)NH 2 ,

heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 4 substituents independently selected from:

oxo,

C 1-4 alkyl substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, and -NH 2 , -NHC(O)H, and

- NHC(O)R xa3 ,

w here R xa3 is selected from C1-6alkyl, and C1-6alkyl substituted from 1 to 6 times by fluoro;

R 62 is selected from:

hydrogen,

C 1-3 alkyl,

aryl,

aryl substituted with from 1 to 4 substituents independently selected

from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 5 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 69 and–NR 66 R 67 ,

where R 66 and R 67 are independently selected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 68 R 69 , where R 68 and R 69 are independently selected from: hydrogen, phenyl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, --CN,

-S(O) 2 NH 2 , and

-S(O) 2 NHCH 3 ,

hetroaryl, and

hetroaryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 5 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 69 and–NR 66 R 67 ,

where R 66 and R 67 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC 1-5 alkyl,

- OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 68 R 69 , where R 68 and R 69 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, -S(O)2NH2, and

-S(O) 2 NHCH 3; and

R 63 and R 64 are independently selected from:

hydrogen,

C 1-4 alkyl,

C 1-4 alkyl substituted with from 1 to 6 substituents

independently selected from: fluoro, heterocycloalkyl, o xo, -NH 2 , C 1-4 alkoxy, and -OH,

heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

-OH, and

C 1-6 alkyl, or

R 63 and R 64 are taken together with the nitrogen to which they are

attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro, chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, -OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and–-CN, heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents i ndependently selected from: C 1-6 alkyl,

- C 1-6 alkylOH, fluoro, chloro, oxo and -OH, C 1-4 alkoxy,

C1-4alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN, oxo,

- NH 2 , -N(H)C 1-4 alkyl,

- N(H)C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl,

heterocycloalkyl, methylheterocycloalkyl,

- OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and –-CN, and

- N(C 1-4 alkyl) 2;

provided that:

R 61 and R 62 are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (VI) neither R 63 nor R 64 is hydrogen.

This invention relates to novel compounds of Formula (VIaar) and to the use of compounds of Formula (VIaar) in the methods of the invention:

wherein:

Y 6aar is selected from: S and NH; R 60aar is selected from: C 1-3 alkyl,

C 1-3 alkyl substituted with from 1 to 6 substituents

independently selected from: fluoro and chloro, - N(H)C 1-3 alkyl,

- N(C 1-3 alkyl) 2 ,

- SC 1-4 alkyl,

C 1-3 alkyloxy,

aryl,

aryl substituted with from one to 3 substituents

independently selected from:

fluoro,

chloro,

-OH, and C 1-3 alkyl,

heteroaryl,

heteroaryl substituted with from one to 3 substituents

independently selected from:

fluoro,

chloro,

-OH, and

C 1-3 alkyl,

cycloalkyl,

cycloalkyl substituted with from one to 3 substituents

independently selected from:

fluoro,

chloro,

-OH, and

C1-3alkyl;

R 61aar is selected from:

hydrogen,

- C(O)NH 2 ,

heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 4 substituents independently selected from:

oxo,

C 1-4 alkyl substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, and -NH 2 , -NHC(O)H, and

- NHC(O)R xa3 ,

w here R xa3 is selected from C1-6alkyl, and C1-6alkyl substituted from 1 to 6 times by fluoro;

R 62aar is selected from:

hydrogen,

C 1-3 alkyl, aryl,

aryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 5 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 69 and–NR 66 R 67 ,

where R 66 and R 67 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 68 R 69 , where R 68 and R 69 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, --CN,

-S(O) 2 NH 2 , and

-S(O) 2 NHCH 3 ,

hetroaryl, and

hetroaryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro, C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 5 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 69 and–NR 66 R 67 ,

where R 66 and R 67 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 68 R 69 , where R 68 and R 69 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, -S(O) 2 NH 2 , and

-S(O) 2 NHCH 3 ;

R 63aar and R 64aar are independently selected from:

hydrogen,

C 1-4 alkyl,

C 1-4 alkyl substituted with from 1 to 6 substituents

independently selected from: fluoro, heterocycloalkyl, o xo, -NH 2 , C 1-4 alkoxy, and -OH,

heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from: fluoro,

chloro,

-OH, and

C 1-6 alkyl, or

R 63aar and R 64aar are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, -OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and–-CN,

heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents i ndependently selected from: C 1-6 alkyl,

- C 1-6 alkylOH, fluoro, chloro, oxo and -OH, C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

oxo,

- NH 2 ,

- N(H)C 1-4 alkyl,

- N(H)C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro,

C 1-4 alkoxy, oxo, phenyl, cycloalkyl,

heterocycloalkyl, methylheterocycloalkyl,

- OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and –-CN, and

- N(C 1-4 alkyl) 2;

provided that:

R 61aar and R 62aar are not both hydrogen, and

R 63aar and R 64aar are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (VIaar) neither R 63aar nor R 64aar is hydrogen. Suitably in the compounds of Formula (VIaar) R 61aar is -C(O)NH 2 . Suitably in the compounds of Formula (VIaar) R 62aar is aryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C1-6alkyl, C 1-6 alkyl substituted with from 1 to 5 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 69 and–NR 66 R 67 ,

where R 66 and R 67 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 68 R 69 , where R 68 and R 69 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH.

This invention relates to novel compounds of Formula (VIa) and to the use of compounds of Formula (VIa) in the methods of the invention:

wherein:

Y 6a is selected from: S and NH; R 60a is selected from: C 1-3 alkyl,

C 1-3 alkyl substituted with from 1 to 6 substituents

independently selected from: fluoro and chloro, - N(H)C 1-3 alkyl,

- N(C 1-3 alkyl) 2 ,

- SC 1-4 alkyl,

C 1-3 alkyloxy,

cycloalkyl, cycloalkyl substituted with from one to 3 substituents

independently selected from:

fluoro,

chloro,

-OH, and

C 1-3 alkyl;

R 61a is selected from:

hydrogen,

- C(O)NH 2 ,

heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 4 substituents independently selected from:

oxo,

C 1-4 alkyl substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, and -NH 2 , -NHC(O)H, and

- NHC(O)R xa3 ,

w here R xa3 is selected from C1-6alkyl, and C1-6alkyl substituted from 1 to 6 times by fluoro;

R 62a is selected from:

hydrogen,

C 1-3 alkyl,

aryl,

aryl substituted with from 1 to 4 substituents independently selected

from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 5 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 69 and–NR 66 R 67 , where R 66 and R 67 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 68 R 69 , where R 68 and R 69 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, --CN,

-S(O) 2 NH 2 , and

-S(O) 2 NHCH 3 ,

hetroaryl, and

hetroaryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 5 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 69 and–NR 66 R 67 ,

where R 66 and R 67 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 68 R 69 , where R 68 and R 69 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, -S(O) 2 NH 2 , and

-S(O) 2 NHCH 3 ;

R 63a and R 64a are independently selected from:

hydrogen,

C 1-4 alkyl,

C 1-4 alkyl substituted with from 1 to 6 substituents

independently selected from: fluoro, heterocycloalkyl, o xo, -NH 2 , C 1-4 alkoxy, and -OH,

heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

-OH, and

C 1-6 alkyl, or

R 63a and R 64a are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from: fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, -OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and–-CN, heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents i ndependently selected from: C 1-6 alkyl,

- C 1-6 alkylOH, fluoro, chloro, oxo and -OH, C 1-4 alkoxy, C 1-4 alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN, oxo,

- NH 2 ,

- N(H)C 1-4 alkyl,

- N(H)C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl,

heterocycloalkyl, methylheterocycloalkyl,

-OH, -NH2, -N(H)C1-4alkyl, -N(C1-4alkyl)2, and –-CN, and

- N(C 1-4 alkyl) 2;

provided that:

R 61a and R 62a are not both hydrogen, and R 63a and R 64a are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (VIa) neither R 63a nor R 64a is hydrogen.

Included in the compounds of the invention and used in the methods of the invention are compounds of Formula (VII):

wherein: Y 7 is selected from: S and NH; R 70 is selected from:

ethyl,

-CH 2 CF 3 ,

- NCH 3 ,

- SCH 3 ,

ethoxy, and

cyclopropyl;

R 71 is selected from:

hydrogen,

- C(O)NH 2 , heterocycloalkyl, and heterocycloalkyl substituted by oxo, -C(O)CH 3 or -NHC(O)CH 3 ;

R 77 is selected from:

hydrogen, C 1-3 alkyl, and aryl,

aryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 79 and–NR 76 R 77 ,

where R 76 and R 77 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 78 R 79 , where R 78 and R 79 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, --CN, S(O) 2 NH 2 , and

-S(O) 2 NHCH 3 ,

pyridinyl,

thiazolyl, and t hiazolyl substituted by -C(O)CH 3 or -NHC(O)CH 3 ; R 72 and R 73 are independently selected from:

hydrogen,

C 1-3 alkyl,

C 1-3 alkyl substituted with from 1 to 3 substituents independently selected from: -OH, oxo, -NH 2 , morpholino and methoxy, 5-oxa-2azaspiro[3.4]octanyl, and

8-azabicyclo[3.2.1]octanyl, or

R 72 and R 73 are taken together with the nitrogen to which they are

attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl selected from:

pyrrolidinyl,

piperidinyl,

1,4diazepanyl,

piperazinyl,

2,9-diazaspiro[5.5]undecanyl,

2,8-diazaspiro[4.5]decanyl,

hexahydro-1H-pyrrolo[1,2a][1,4]diazepinyl,

morpholinyl,

1-oxa-6-azaspiro[3.4]octanyl,

1,7-diazaspiro[3.5]nonanyl,

2,7-diazaspiro[3.5]nonanyl,

2,6-diazaspiro[3.4]octanyl,

azetidinyl,

1,8-diazaspiro[4.5]decanyl, and

5-oxa-2-azaspiro[3.4]octanyl, all of which are optionally substituted with from 1 to 5 substituents independently selected from: fluoro,

oxo,

-OH,

- CH 3 ,

- CH 2 OH,

methoxy,

- CH 2 CH 3 ,

- C(O)CH 3 ,

- CH 2 CH 2 OH,

- CH 2 CH 2 CH 3 , -CH 2 CH 2 OCH 3 ,

- CH 2 CH(OH)CH 3 ,

- CH 2 C(O)OCH 3 ,

- C(O)CH(CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 CH 2 N(CH 3 ) 2 ,

-OCH 2 CH 2 NH 2 ,

-NH 2 ,

- NHCH 3 ,

- N(CH 3 ) 2 ,

- NHC(O)-CNH 2 (CH 3 ) 2 ,

- NHC(O)CH 2 NH 2 ,

- NHC(O)CHCH 3 NH 2 ,

-NHC(O)-CNH2(CH3)2, -NHC(O)aminotetrahydropyranyl,

- CH 2 NH 2 ,

- CH 2 CH 2 NH 2 ,

- CH 2 CH 2 CH 2 NH 2 ,

- CH 2 N(CH 3 ) 2 ,

-C(O)aminooxetanyl,

- S(O) 2 CH 2 CH 3 ,

- S(O) 2 CH 3 ,

benzoyl,

3-pyrrolidinylpropyl,

cyclopropylmethyl,

piperidinyl,

morpholinyl,

morpholinylmethyl,

methylpiperazinylmethyl,

pyrrolidinyl,

pyrrolidinylmethyl,

piperazinylmethyl,

oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl; provided that:

R 71 and R 77 are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (VII) neither R 72 nor R 73 is hydrogen. This invention relates to novel compounds of Formula (VIIaar) and to the use of compounds of Formula (VIIaar) in the methods of the invention:

wherein: Y 7aar is selected from: S and NH; R 70aar is selected from:

ethyl,

-CH 2 CF 3 ,

- NCH 3 ,

- SCH 3 ,

ethoxy,

methoxy,

phenyl,

furanyl, and

cyclopropyl;

R 71aar is selected from:

hydrogen,

- C(O)NH 2 , heterocycloalkyl, and

h eterocycloalkyl substituted by oxo, -C(O)CH 3 or -NHC(O)CH 3 ;

R 77aar is selected from:

hydrogen, C 1-3 alkyl, and aryl,

aryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 79a and–NR 76a R 77a ,

where R 76a and R 77a are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 78a R 79a , where R 78a and R 79a are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, --CN,

S(O) 2 NH 2 , and

-S(O) 2 NHCH 3 ,

pyridinyl,

thiazolyl, and thiazolyl substituted by -C(O)CH 3 or -NHC(O)CH 3 ; R 72aar and R 73aar are independently selected from:

hydrogen,

C 1-3 alkyl,

C 1-3 alkyl substituted with from 1 to 3 substituents independently selected from: -OH, oxo, -NH2, morpholino and methoxy, 5-oxa-2azaspiro[3.4]octanyl, and

8-azabicyclo[3.2.1]octanyl, or

R 72aar and R 73aar are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl selected from:

pyrrolidinyl,

piperidinyl,

1,4diazepanyl,

piperazinyl,

2,9-diazaspiro[5.5]undecanyl,

2,8-diazaspiro[4.5]decanyl,

hexahydro-1H-pyrrolo[1,2a][1,4]diazepinyl,

morpholinyl,

1-oxa-6-azaspiro[3.4]octanyl,

1,7-diazaspiro[3.5]nonanyl,

2,7-diazaspiro[3.5]nonanyl,

2,6-diazaspiro[3.4]octanyl,

azetidinyl,

1,8-diazaspiro[4.5]decanyl, and

5-oxa-2-azaspiro[3.4]octanyl,

all of which are optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

oxo,

-OH,

- CH 3 ,

- CH 2 OH, methoxy,

- CH 2 CH 3 ,

- C(O)CH 3 ,

- CH 2 CH 2 OH,

- CH 2 CH 2 CH 3 ,

- CH 2 CH 2 OCH 3 ,

- CH 2 CH(OH)CH 3 ,

- CH 2 C(O)OCH 3 ,

- C(O)CH(CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 ,

- CH 2 CH 2 CH 2 N(CH 3 ) 2 , -OCH 2 CH 2 NH 2 ,

-OCH 2 CH 2 OH,

-NH 2 ,

- NHCH 3 ,

- N(CH 3 ) 2 ,

- NHC(O)-CNH 2 (CH 3 ) 2 , -NHC(O)CH 2 NH 2 ,

- NHC(O)CHCH 3 NH 2 ,

- NHC(O)-CNH 2 (CH 3 ) 2 , -NHC(O)aminotetrahydropyranyl, -CH 2 NH 2 ,

- CH 2 CH 2 NH 2 ,

- CH 2 CH 2 CH 2 NH 2 ,

- CH 2 N(CH 3 ) 2 , -C(O)aminooxetanyl,

-C(O)aminotetrahydropyranyl,

- S(O) 2 CH 2 CH 3 ,

- S(O) 2 CH 3 ,

benzoyl,

3-pyrrolidinylpropyl,

cyclopropylmethyl,

piperidinyl,

morpholinyl,

morpholinylmethyl,

methylpiperazinylmethyl,

methylpiperazinyl,

pyrrolidinyl,

pyrrolidinylmethyl,

piperazinylmethyl,

oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl;

provided that:

R 72aar and R 73aar are not both hydrogen, and

R 71aar and R 77aar are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (VIIaar) neither R 72aar nor R 73aar is hydrogen. Suitably in the compounds of Formula (VIIaar) R 71aar is -C(O)NH 2 . Suitably in the compounds of Formula (VIIaar) R 77aar is aryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 79a and–NR 76a R 77a ,

where R 76a and R 77a are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 78a R 79a , where R 78a and R 79a are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH.

This invention relates to novel compounds of Formula (VIIa) and to the use of compounds of Formula (VIIa) in the methods of the invention:

wherein: Y 7a is selected from: S and NH; R 70a is selected from: ethyl,

-CH 2 CF 3 ,

- NCH 3 ,

- SCH 3 ,

ethoxy, and

cyclopropyl;

R 71a is selected from:

hydrogen,

- C(O)NH 2 , heterocycloalkyl, and

h eterocycloalkyl substituted by oxo, -C(O)CH 3 or -NHC(O)CH 3 ;

R 77a is selected from:

hydrogen, C 1-3 alkyl, and aryl,

aryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 79a and–NR 76a R 77a ,

where R 76a and R 77a are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC 1-5 alkyl,

- OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 78a R 79a , where R 78a and R 79a are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, --CN,

S(O) 2 NH 2 , and

-S(O) 2 NHCH 3 ,

pyridinyl,

thiazolyl, and t hiazolyl substituted by -C(O)CH 3 or -NHC(O)CH 3 ;

R 72a and R 73a are independently selected from:

hydrogen,

C 1-3 alkyl,

C 1-3 alkyl substituted with from 1 to 3 substituents independently selected from: -OH, oxo, -NH 2 , morpholino and methoxy,

5-oxa-2azaspiro[3.4]octanyl, and

8-azabicyclo[3.2.1]octanyl, or

R d R 73a

are taken together with the nitrogen to which they are

attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl selected from:

pyrrolidinyl,

piperidinyl,

1,4diazepanyl,

piperazinyl, 2,9-diazaspiro[5.5]undecanyl,

2,8-diazaspiro[4.5]decanyl,

hexahydro-1H-pyrrolo[1,2a][1,4]diazepinyl, morpholinyl,

1-oxa-6-azaspiro[3.4]octanyl,

1,7-diazaspiro[3.5]nonanyl,

2,7-diazaspiro[3.5]nonanyl,

2,6-diazaspiro[3.4]octanyl,

azetidinyl,

1,8-diazaspiro[4.5]decanyl, and

5-oxa-2-azaspiro[3.4]octanyl,

all of which are optionally substituted with from 1 to 5 substituents independently selected from: fluoro,

oxo,

-OH,

- CH 3 , -CH 2 OH,

methoxy,

- CH 2 CH 3 ,

- C(O)CH 3 ,

- CH 2 CH 2 OH,

- CH 2 CH 2 CH 3 ,

- CH 2 CH 2 OCH 3 ,

- CH 2 CH(OH)CH 3 ,

- CH 2 C(O)OCH 3 ,

- C(O)CH(CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 CH 2 N(CH 3 ) 2 , -OCH 2 CH 2 NH 2 ,

-NH 2 ,

- NHCH 3 ,

- N(CH 3 ) 2 ,

- NHC(O)-CNH 2 (CH 3 ) 2 , -NHC(O)CH 2 NH 2 ,

- NHC(O)CHCH 3 NH 2 ,

- NHC(O)-CNH 2 (CH 3 ) 2 , -NHC(O)aminotetrahydropyranyl, - CH 2 NH 2 ,

- CH 2 CH 2 NH 2 ,

- CH 2 CH 2 CH 2 NH 2 ,

- CH 2 N(CH 3 ) 2 ,

-C(O)aminooxetanyl,

- S(O) 2 CH 2 CH 3 ,

- S(O) 2 CH 3 ,

benzoyl,

3-pyrrolidinylpropyl, cyclopropylmethyl, piperidinyl,

morpholinyl,

morpholinylmethyl, methylpiperazinylmethyl, pyrrolidinyl,

pyrrolidinylmethyl,

piperazinylmethyl,

oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl;

provided that: R 72a and R 73a are not both hydrogen, and

R 71a and R 77a are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (VIIa) neither R 72a nor R 73a is hydrogen.

Included in the compounds of the invention and used in the methods of the invention are compounds of Formula (VIII):

wherein:

Y 8 is selected from: S and NH; R 80 is selected from:

ethyl,

-CH 2 CF 3 ,

- NCH 3 ,

- SCH 3 ,

ethoxy, and

cyclopropyl;

R 81 is selected from:

hydrogen,

- C(O)NH 2 , heterocycloalkyl, and

h eterocycloalkyl substituted by oxo, -C(O)CH 3 or -NHC(O)CH 3 ;

R 87 is selected from:

hydrogen,

CH 3 ,

phenyl,

phenyl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 89 and–NR 86 R 87 ,

where R 86 and R 87 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 88 R 89 , where R 88 and R 89 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, --CN, S(O) 2 NH 2 , and -S(O) 2 NHCH 3 ,

pyridinyl,

thiazolyl, and t hiazolyl substituted by -C(O)CH 3 or -NHC(O)CH 3 ;

R 82 and R 83 are independently selected from:

hydrogen,

C 1-3 alkyl,

C 1-3 alkyl substituted with from 1 to 3 substituents independently selected from: -OH, oxo, -NH2, morpholino and methoxy, 5-oxa-2azaspiro[3.4]octanyl, and

8-azabicyclo[3.2.1]octanyl, or

R 82 and R 83 are taken together with the nitrogen to which they are

attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl selected from:

pyrrolidinyl,

piperidinyl,

1,4diazepanyl,

piperazinyl,

2,9-diazaspiro[5.5]undecanyl,

2,8-diazaspiro[4.5]decanyl,

hexahydro-1H-pyrrolo[1,2a][1,4]diazepinyl,

morpholinyl,

1-oxa-6-azaspiro[3.4]octanyl,

1,7-diazaspiro[3.5]nonanyl,

2,7-diazaspiro[3.5]nonanyl,

2,6-diazaspiro[3.4]octanyl,

azetidinyl,

1,8-diazaspiro[4.5]decanyl, and

5-oxa-2-azaspiro[3.4]octanyl,

all of which are optionally substituted with from 1 to 5 substituents independently selected from: fluoro,

oxo,

-OH,

- CH 3 ,

- CH 2 OH,

methoxy,

-CH2CH3, -C(O)CH3, -CH 2 CH 2 OH,

- CH 2 CH 2 CH 3 ,

- CH 2 CH 2 OCH 3 ,

- CH 2 CH(OH)CH 3 , -CH 2 C(O)OCH 3 ,

- C(O)CH(CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 ,

- CH 2 CH 2 CH 2 N(CH 3 ) 2 ,

-OCH 2 CH 2 NH 2 ,

-NH2,

- NHCH 3 ,

- N(CH 3 ) 2 , -NHC(O)-CNH 2 (CH 3 ) 2 ,

- NHC(O)CH 2 NH 2 ,

- NHC(O)CHCH 3 NH 2 ,

- NHC(O)-CNH 2 (CH 3 ) 2 ,

-NHC(O)aminotetrahydropyranyl, -CH 2 NH 2 ,

- CH 2 CH 2 NH 2 , -CH 2 CH 2 CH 2 NH 2 ,

- CH 2 N(CH 3 ) 2 ,

-C(O)aminooxetanyl,

- S(O) 2 CH 2 CH 3 , -S(O) 2 CH 3 ,

benzoyl,

3-pyrrolidinylpropyl,

cyclopropylmethyl,

piperidinyl,

morpholinyl,

morpholinylmethyl,

methylpiperazinylmethyl,

pyrrolidinyl,

pyrrolidinylmethyl,

piperazinylmethyl,

oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl;

provided that:

R 81 and R 87 are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (VIII) neither R 82a nor R 83a is hydrogen.

This invention relates to novel compounds of Formula (VIIIaar) and to the use of compounds of Formula (VIIIaar) in the methods of the invention: wherein: Y 8aar is selected from: S and NH; R 80aar is selected from:

ethyl,

-CH 2 CF 3 ,

- NCH 3 ,

- SCH 3 ,

ethoxy,

methoxy,

phenyl,

furanyl, and

cyclopropyl;

R 81aar is selected from:

hydrogen,

- C(O)NH 2 , heterocycloalkyl, and

h eterocycloalkyl substituted by oxo, -C(O)CH 3 or -NHC(O)CH 3 ; R 87aar is selected from:

hydrogen,

CH 3 ,

phenyl,

phenyl substituted with from 1 to 4 substituents independently selected from:

fluoro, chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 89 and–NR 86 R 87 ,

where R 86 and R 87 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 88 R 89 , where R 88 and R 89 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, --CN,

-S(O) 2 NH 2 , and -S(O) 2 NHCH 3 ,

pyridinyl,

thiazolyl, and

t hiazolyl substituted by -C(O)CH 3 or -NHC(O)CH 3 ;

R 82aar and R 83aar are independently selected from:

hydrogen,

C 1-3 alkyl, C 1-3 alkyl substituted with from 1 to 3 substituents independently selected from: -OH, oxo, -NH 2 , morpholino and methoxy,

5-oxa-2azaspiro[3.4]octanyl, and

8-azabicyclo[3.2.1]octanyl, or

R 82aar and R 83aar are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl selected from:

pyrrolidinyl,

piperidinyl,

1,4diazepanyl,

piperazinyl,

2,9-diazaspiro[5.5]undecanyl,

2,8-diazaspiro[4.5]decanyl,

hexahydro-1H-pyrrolo[1,2a][1,4]diazepinyl,

morpholinyl,

1-oxa-6-azaspiro[3.4]octanyl,

1,7-diazaspiro[3.5]nonanyl,

2,7-diazaspiro[3.5]nonanyl,

2,6-diazaspiro[3.4]octanyl,

azetidinyl,

1,8-diazaspiro[4.5]decanyl, and

5-oxa-2-azaspiro[3.4]octanyl,

all of which are optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

oxo,

-OH,

- CH 3 , -CH 2 OH,

methoxy,

- CH 2 CH 3 ,

- C(O)CH 3 , -CH 2 CH 2 OH,

- CH 2 CH 2 CH 3 , -CH 2 CH 2 OCH 3 ,

- CH 2 CH(OH)CH 3 ,

- CH 2 C(O)OCH 3 ,

- C(O)CH(CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 ,

- CH 2 CH 2 CH 2 N(CH 3 ) 2 , -OCH 2 CH 2 NH 2 ,

-OCH 2 CH 2 OH,

-NH 2 ,

- NHCH 3 ,

- N(CH 3 ) 2 ,

- NHC(O)-CNH 2 (CH 3 ) 2 , -NHC(O)CH 2 NH 2 , -NHC(O)CHCH 3 NH 2 ,

- NHC(O)-CNH 2 (CH 3 ) 2 , -NHC(O)aminotetrahydropyranyl, -CH 2 NH 2 ,

- CH 2 CH 2 NH 2 ,

- CH 2 CH 2 CH 2 NH 2 ,

- CH 2 N(CH 3 ) 2 ,

-C(O)aminooxetanyl,

-C(O)aminotetrahydropyranyl, -S(O) 2 CH 2 CH 3 , -S(O) 2 CH 3 ,

benzoyl,

3-pyrrolidinylpropyl,

cyclopropylmethyl,

piperidinyl,

morpholinyl,

morpholinylmethyl,

methylpiperazinylmethyl,

methylpiperazinyl,

pyrrolidinyl,

pyrrolidinylmethyl,

piperazinylmethyl,

oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl;

provided that:

R 81aar and R 87aar are not both hydrogen, and

R 82aar and R 83aar are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (VIIIaar) neither R 82aar nor R 83aar is hydrogen. Suitably in the compounds of Formula (VIIIaar) R 81aar is -C(O)NH 2 . Suitably in the compounds of Formula (VIIIaar) R 87aar is phenyl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 89 and–NR 86 R 87 , where R 86 and R 87 are independently

s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 88 R 89 , where R 88 and R 89 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH.

This invention relates to novel compounds of Formula (VIIIa) and to the use of compounds of Formula (VIIIa) in the methods of the invention:

wherein:

Y 8a is selected from: S and NH; R 80a is selected from:

ethyl,

-CH 2 CF 3 , -NCH 3 ,

- SCH 3 ,

ethoxy, and

cyclopropyl;

R 81a is selected from:

hydrogen,

- C(O)NH 2 , heterocycloalkyl, and

h eterocycloalkyl substituted by oxo, -C(O)CH 3 or -NHC(O)CH 3 ;

R 87a is selected from:

hydrogen,

CH 3 ,

phenyl,

phenyl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 89 and–NR 86 R 87 ,

where R 86 and R 87 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 88 R 89 , where R 88 and R 89 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, --CN,

-S(O) 2 NH 2 , and -S(O) 2 NHCH 3 ,

pyridinyl,

thiazolyl, and

t hiazolyl substituted by -C(O)CH 3 or -NHC(O)CH 3 ;

R 82a and R 83a are independently selected from:

hydrogen,

C 1-3 alkyl,

C 1-3 alkyl substituted with from 1 to 3 substituents independently selected from: -OH, oxo, -NH 2 , morpholino and methoxy, 5-oxa-2azaspiro[3.4]octanyl, and

8-azabicyclo[3.2.1]octanyl, or

R 82a and R 83a are taken together with the nitrogen to which they are

attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl selected from:

pyrrolidinyl,

piperidinyl,

1,4diazepanyl,

piperazinyl,

2,9-diazaspiro[5.5]undecanyl,

2,8-diazaspiro[4.5]decanyl, hexahydro-1H-pyrrolo[1,2a][1,4]diazepinyl, morpholinyl,

1-oxa-6-azaspiro[3.4]octanyl,

1,7-diazaspiro[3.5]nonanyl,

2,7-diazaspiro[3.5]nonanyl,

2,6-diazaspiro[3.4]octanyl,

azetidinyl,

1,8-diazaspiro[4.5]decanyl, and

5-oxa-2-azaspiro[3.4]octanyl,

all of which are optionally substituted with from 1 to 5 substituents independently selected from: fluoro,

oxo,

-OH,

- CH 3 , -CH 2 OH,

methoxy,

- CH 2 CH 3 ,

- C(O)CH 3 , -CH 2 CH 2 OH,

- CH 2 CH 2 CH 3 ,

- CH 2 CH 2 OCH 3 ,

- CH 2 CH(OH)CH 3 ,

- CH 2 C(O)OCH 3 , -C(O)CH(CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 ,

- CH 2 CH 2 CH 2 N(CH 3 ) 2 ,

-OCH 2 CH 2 NH 2 ,

-NH 2 , -NHCH 3 ,

- N(CH 3 ) 2 , -NHC(O)-CNH 2 (CH 3 ) 2 , -NHC(O)CH 2 NH 2 ,

- NHC(O)CHCH 3 NH 2 ,

- NHC(O)-CNH 2 (CH 3 ) 2 , -NHC(O)aminotetrahydropyranyl, - CH 2 NH 2 ,

- CH 2 CH 2 NH 2 ,

- CH 2 CH 2 CH 2 NH 2 ,

- CH 2 N(CH 3 ) 2 ,

-C(O)aminooxetanyl,

- S(O) 2 CH 2 CH 3 ,

- S(O) 2 CH 3 ,

benzoyl,

3-pyrrolidinylpropyl, cyclopropylmethyl, piperidinyl,

morpholinyl,

morpholinylmethyl, methylpiperazinylmethyl, pyrrolidinyl,

pyrrolidinylmethyl,

piperazinylmethyl,

oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl;

provided that:

R 81a and R 87a are not both hydrogen, and

R 82a and R 83a are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (VIIIa) neither R 82a nor R 83a is hydrogen.

This invention relates to novel compounds of Formula (Q) and to the use of compounds of Formula (Q) in the methods of the invention:

wherein: Y 7a’ is selected from: S and NH; R 70a’ is selected from:

ethyl,

-CH 2 CF 3 , and

cyclopropyl;

R 71a’ is selected from:

hydrogen,

CH3,

phenyl,

phenyl substituted with chloro, and

pyridine,

R 77a’ is selected from: - C(O)NH 2 , and aryl,

aryl substituted with from 1 to 4 substituents independently selected

from: fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 79a’ and–NR 76a’ R 77a’ ,

where R 76a’ and R 77a’ are independently s elected form: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 78a’ R 79a’ , where R 78a’ and R 79a’ are independently selected f orm: hydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituentsindependently selected from: f luoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and –COOH,

- S(O) 2 NH 2 , -S(O) 2 NHCH 3 , and R 72a’ and R 73a’ are independently selected from:

hydrogen,

C 1-3 alkyl,

C 1-3 alkyl substituted with from 1 to 3 substituents

independently selected from: morpholino and methoxy, 5-oxa-2azaspiro[3.4]octan, and

8-azabicyclo[3.2.1]octan, or

R 72a’ and R 73a’ are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl selected from:

pyrrolidinyl,

piperidinyl,

1,4diazepan,

piperazinyl,

2,9-diazaspiro[5.5]undecan,

2,8-diazaspiro[4.5]decan,

octahydro-1H-pyrrolo[1,2a][1,4]diazepin, morpholin,

1-oxa-6-azaspiro[3.4]octan,

1,7-diazaspiro[3.5]nonan,

2,7-diazaspiro[3.5]nonan,

2,6-diazaspiro[3.4]octan,

azetidin,

1,8-diazaspiro[4.5]decan, and

5-oxa-2-azaspiro[3.4]octan,

all of which are optionally substituted with from 1 to 5 substituents independently selected from: fluoro,

oxo,

-OH,

- CH 3 ,

- CH 2 OH,

methoxy,

- CH 2 CH 3 ,

- C(O)CH 3 ,

- CH 2 CH 2 OH,

- CH 2 CH 2 CH 3 , -CH 2 CH 2 OCH 3 , -CH 2 CH(OH)CH 3 , -CH 2 C(O)OCH 3 , -C(O)CH(CH 3 ) 2 , -CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 CH 2 N(CH 3 ) 2 , -NH 2 ,

- NHCH 3 ,

- N(CH 3 ) 2 ,

- CH 2 NH 2 , -CH 2 CH 2 NH 2 , -CH 2 CH 2 CH 2 NH 2 , -CH 2 N(CH 3 ) 2 , -S(O) 2 CH 2 CH 3 , -S(O) 2 CH 3 , benzoyl,

3-pyrrolidinylpropyl, 2-cyclopropylmethyl, piperidinyl, morpholinyl, morpholinylmethyl, methylpiperazinylmethyl, pyrrolidinyl, pyrrolidinylmethyl, piperazinylmethyl, oxoimidazolidinyl, and 2-hydroxyethylpiperidinyl; provided that: R 72a and R 73a are not both hydrogen; or a pharmaceutically acceptable salts thereof.

Suitably in the compounds of Formula (Q) neither R 72a’ nor R 73a’ is hydrogen.

This invention relates to novel compounds of Formula (T) and to the use of compounds of Formula (T) in the methods of the invention:

wherein:

R 80 is selected from:

ethyl,

-CH 2 CF 3 , and

cyclopropyl;

R 81 is selected from:

phenyl, and

phenyl substituted with chloro or fluoro, and

R 72a’ and R 73a’ are independently selected from: C 1-3 alkyl,

C 1-3 alkyl substituted with from 1 to 3 substituents

independently selected from: oxo, and NH 2 , or R 72a’ and R 73a’ are taken together with the nitrogen to which they are

attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl selected from:

pyrrolidinyl,

piperidinyl,

1,4diazepan,

piperazinyl,

2,9-diazaspiro[5.5]undecan,

2,8-diazaspiro[4.5]decan,

octahydro-1H-pyrrolo[1,2a][1,4]diazepin, morpholin,

1-oxa-6-azaspiro[3.4]octan,

1,7-diazaspiro[3.5]nonan,

2,7-diazaspiro[3.5]nonan,

2,6-diazaspiro[3.4]octan,

azetidin,

1,8-diazaspiro[4.5]decan, and

5-oxa-2-azaspiro[3.4]octan,

all of which are optionally substituted with from 1 to 5 substituents independently selected from: fluoro,

oxo,

-OH,

- CH 3 ,

- CH 2 OH,

methoxy,

- CH 2 CH 3 ,

- C(O)CH 3 ,

- CH 2 CH 2 OH, -CH 2 CH 2 CH 3 ,

- CH 2 CH 2 OCH 3 ,

- CH 2 CH(OH)CH 3 ,

- CH 2 C(O)OCH 3 , -C(O)CH(CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 CH 2 N(CH 3 ) 2 , -NH 2 ,

- NHCH 3 , -N(CH 3 ) 2 ,

- NHCH 2 C(CH 3 ) 3 , -N(CH 3 )cyclobutane, -CH 2 NH 2 ,

- CH 2 CH 2 NH 2 , -CH 2 CH 2 CH 2 NH 2 , -CH 2 N(CH 3 ) 2 , -S(O) 2 CH 2 CH 3 , -S(O) 2 CH 3 , benzoyl,

3-pyrrolidinylpropyl, 2-cyclopropylmethyl, piperidinyl, morpholinyl, morpholinylmethyl, methylpiperazinylmethyl, pyrrolidinyl, pyrrolidinylmethyl, piperazinylmethyl, oxoimidazolidinyl, and 2-hydroxyethylpiperidinyl; or a pharmaceutically acceptable salt or prodrug thereof. Suitably in the compounds of Formula (T), the compounds are in the form of a phosphate prodrug.

This invention relates to novel compounds of Formula (Ta) and to the use of compounds of Formula (Ta) in the methods of the invention:

wherein: R 80a is selected from:

ethyl,

-CH 2 CF 3 , and

cyclopropyl;

R 81a is selected from:

phenyl, and

phenyl substituted with chloro or fluoro, and

R 82a and R 83a are taken together with the nitrogen to which they are

attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl selected from:

pyrrolidinyl,

piperidinyl,

1,4diazepan,

piperazinyl,

2,9-diazaspiro[5.5]undecan,

2,8-diazaspiro[4.5]decan,

octahydro-1H-pyrrolo[1,2a][1,4]diazepin,

morpholin, 1-oxa-6-azaspiro[3.4]octan,

1,7-diazaspiro[3.5]nonan,

2,7-diazaspiro[3.5]nonan,

2,6-diazaspiro[3.4]octan,

azetidin,

1,8-diazaspiro[4.5]decan, and

5-oxa-2-azaspiro[3.4]octan,

all of which are optionally substituted with from 1 to 5 substituents independently selected from: fluoro,

oxo,

-OH,

- CH 3 ,

- CH 2 OH,

methoxy,

- CH 2 CH 3 ,

- C(O)CH 3 ,

- CH 2 CH 2 OH,

- CH 2 CH 2 CH 3 ,

- CH 2 CH 2 OCH 3 , -CH 2 CH(OH)CH 3 ,

- CH 2 C(O)OCH 3 ,

- C(O)CH(CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 ,

- CH 2 CH 2 CH 2 N(CH 3 ) 2 ,

-NH 2 ,

- NHCH 3 ,

- N(CH 3 ) 2 , -NHCH 2 C(CH 3 ) 3 ,

- N(CH 3 )cyclobutane, -CH 2 NH 2 ,

- CH 2 CH 2 NH 2 ,

- CH 2 CH 2 CH 2 NH 2 ,

- CH 2 N(CH 3 ) 2 ,

- S(O) 2 CH 2 CH 3 ,

- S(O) 2 CH 3 ,

benzoyl,

3-pyrrolidinylpropyl,

2-cyclopropylmethyl,

piperidinyl,

morpholinyl,

morpholinylmethyl,

methylpiperazinylmethyl,

pyrrolidinyl,

pyrrolidinylmethyl,

piperazinylmethyl,

oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (Ta), the compounds are in the form of a phosphate prodrug. This invention relates to novel compounds of Formula (S) and to the use of compounds of Formula (S) in the methods of the invention:

wherein: R 90 is selected from:

ethyl,

-CH2CF3, and

cyclopropyl;

R 91 is selected from:

phenyl, and

phenyl substituted with from 1 to 2 substituents independently selected from:

fluoro,

chloro,

C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, oxo, - OH, -NH 2 , -NHCH 3 , and–N(CH3)2,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, bromo, i odo, oxo, -S(O) 2 CH 3 , --CN, -OR79a’ and –NR 76a’ R 77a’ ,

where R 76a’ and R 77a’ are independently selected form: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 78a’ R 79a’ , where R 78a’ and R 79a’ are independently selected form: hydrogen, phenyl, C1-5alkyl and C 1-5 alkyl substituted with from 1 to 4 substituentsindependently selected from: f luoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and –COOH,

tetrahydroisothiazolyl,

tetrahydroisothiazolyl substituted twice by oxo, tetrahydro-1,2-thiazinyl,

tetrahydro-1,2-thiazinyl substituted twice by oxo, - N(CH 3 )S(O) 2 CH 3 ,

- N(CH 3 )S(O) 2 CFH 2 ,

- N(CH 3 )S(O) 2 CF 2 H,

- N(CH 3 )S(O) 2 CF 3 ,

- OS(O) 2 CH 3 ,

-S(O) 2 NH 2 , and -S(O) 2 NHCH 3 , and R 92 and R 93 are independently selected from: C 1-3 alkyl, C 1-3 alkyl substituted with from 1 to 3 substituents

i ndependently selected from: oxo, -N(CH 2 CH 3 ) 3 , -CH 2 CH 2 piperidinyl, and NH 2 , or

R 92 and R 93 are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl selected from:

pyrrolidinyl,

piperidinyl,

1,4diazepan,

piperazinyl,

2,9-diazaspiro[5.5]undecan,

2,8-diazaspiro[4.5]decan,

octahydro-1H-pyrrolo[1,2a][1,4]diazepin, morpholin,

1-oxa-6-azaspiro[3.4]octan,

1,7-diazaspiro[3.5]nonan,

2,7-diazaspiro[3.5]nonan,

2,6-diazaspiro[3.4]octan,

azetidin,

1,8-diazaspiro[4.5]decan, and

5-oxa-2-azaspiro[3.4]octan,

all of which are optionally substituted with from 1 to 5 substituents independently selected from: fluoro,

oxo,

-OH,

- CH 3 ,

- CH 2 OH,

methoxy,

- CH 2 CH 3 , -C(O)CH 3 , -CH 2 CH 2 OH, -CH 2 CH 2 CH 3 , -CH 2 CH 2 OCH 3 , -CH 2 CH(OH)CH 3 , -CH 2 C(O)OCH 3 , -C(O)CH(CH 3 ) 2 , -CH 2 CH 2 N(CH 3 ) 2 , -CH 2 N(CH 3 ) 2 , -CH 2 CH 2 CH 2 N(CH 3 ) 2 , -NH 2 ,

- NHCH 3 ,

- N(CH 3 ) 2 ,

- NHCH 2 C(CH 3 ) 3 , -NHCH(CH 3 ) 2 , -NHC(O)CH(CH 3 )(NH 2 ), -NHC(O)C(CH 3 ) 3 , -N(CH 3 )cyclobutane, -CH2NH2,

-CH2pyrrolidinyl, -CH 2 CH 2 NH 2 , -CH 2 CH 2 CH 2 NH 2 , -CH 2 N(CH 3 ) 2 , -S(O) 2 CH 2 CH 3 , -S(O) 2 CH 3 , benzoyl,

3-pyrrolidinylpropyl,

2-cyclopropylmethyl,

piperidinyl,

morpholinyl,

morpholinylmethyl,

methylpiperazinylmethyl,

pyrrolidinyl,

pyrrolidinylmethyl,

piperazinylmethyl,

oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (S), the compounds are in the form of a phosphate prodrug.

This invention relates to novel compounds of Formula (Sa) and to the use of compounds of Formula (Sa) in the methods of the invention:

wherein:

R 90a is selected from:

ethyl,

-CH 2 CF 3 , and

cyclopropyl;

R 91a is selected from: phenyl, and

phenyl substituted with from 1 to 2 substituents independently selected from:

fluoro,

chloro,

C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, oxo, - OH, -NH 2 , -NHCH 3 , and–N(CH3)2,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, bromo, i odo, oxo, -S(O) 2 CH 3 , --CN, -OR79a’ and –NR 76a’ R 77a’ ,

where R 76a’ and R 77a’ are independently selected form: hydrogen, -S(O)2CH3, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 78a’ R 79a’ , where R 78a’ and R 79a’ are independently selected f orm: hydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituentsindependently selected from: f luoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and –COOH, tetrahydroisothiazolyl,

tetrahydroisothiazolyl substituted twice by oxo, tetrahydro-1,2-thiazinyl,

tetrahydro-1,2-thiazinyl substituted twice by oxo, - N(CH 3 )S(O) 2 CH 3 ,

- N(CH 3 )S(O) 2 CFH 2 ,

- N(CH 3 )S(O) 2 CF 2 H,

- N(CH 3 )S(O) 2 CF 3 ,

- OS(O) 2 CH 3 ,

-S(O) 2 NH 2 , and -S(O) 2 NHCH 3 , and R 92a and R 93a are independently selected from: C 1-3 alkyl,

C 1-3 alkyl substituted with from 1 to 3 substituents independently selected from: oxo, -N(CH 2 CH 3 ) 3 , -CH 2 CH 2 piperidinyl, and NH 2 , or

R 92a and R 93a are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl selected from:

pyrrolidinyl,

piperidinyl,

1,4diazepan,

piperazinyl,

2,9-diazaspiro[5.5]undecan, 2,8-diazaspiro[4.5]decan,

octahydro-1H-pyrrolo[1,2a][1,4]diazepin, morpholin,

1-oxa-6-azaspiro[3.4]octan, 1,7-diazaspiro[3.5]nonan, 2,7-diazaspiro[3.5]nonan,

2,6-diazaspiro[3.4]octan,

azetidin,

1,8-diazaspiro[4.5]decan, and

5-oxa-2-azaspiro[3.4]octan,

all of which are optionally substituted with from 1 to 5 substituents independently selected from: fluoro,

oxo,

-OH,

- CH 3 ,

- CH 2 OH,

methoxy,

- CH 2 CH 3 ,

- C(O)CH 3 ,

- CH 2 CH 2 OH,

-CH2CH2CH3, - CH 2 CH 2 OCH 3 , -CH 2 CH(OH)CH 3 ,

- CH 2 C(O)OCH 3 ,

- C(O)CH(CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 ,

- CH 2 N(CH 3 ) 2 ,

- CH 2 CH 2 CH 2 N(CH 3 ) 2 ,

-NH 2 ,

- NHCH 3 ,

- N(CH 3 ) 2 , -NHCH 2 C(CH 3 ) 3 ,

- NHCH(CH 3 ) 2 , -NHC(O)CH(CH 3 )(NH 2 ), -NHC(O)C(CH 3 ) 3 , -N(CH 3 )cyclobutane, -CH 2 NH 2 ,

- CH 2 pyrrolidinyl, -CH 2 CH 2 NH 2 , -CH 2 CH 2 CH 2 NH 2 , -CH 2 N(CH 3 ) 2 , -S(O) 2 CH 2 CH 3 , -S(O) 2 CH 3 , benzoyl,

3-pyrrolidinylpropyl, 2-cyclopropylmethyl, piperidinyl, morpholinyl, morpholinylmethyl, methylpiperazinylmethyl, pyrrolidinyl, pyrrolidinylmethyl, piperazinylmethyl, oxoimidazolidinyl, and 2-hydroxyethylpiperidinyl; or a pharmaceutically acceptable salt or prodrug thereof. Suitably in the compounds of Formula (Sa), the compounds are in the form of a phosphate prodrug.

Primary Amide This invention relates to compounds of Formula (Ibr) and to the use of compounds of Formula (Ibr) in the methods of the invention:

wherein: X 1br and X 2br are independently selected from: hydrogen,

--CN,

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

- OC 1-6 alkyl,

- OR e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d ,

heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R d ,

-SH, and

- SR a ; Y br is selected from: S, NH, NR z , O, S(O), and S(O)2; R 1br is selected from: - NH 2 , -NHR a ,

- NR b R c ,

--CN,

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

- OC 1-6 alkyl,

- OR e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R d , aryl,

a ryl substituted from 1 to 4 times by R d , heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d , -SH, and

- SR a ; R 3br is selected from: hydrogen,

C 1-6 alkyl,

R e ,

heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R d , aryl,

a ryl substituted from 1 to 4 times by R d , heteroaryl, and

h eteroaryl substituted from 1 to 4 times by R d ; and R 5br is selected from: - NH 2 ,

- NHR a , -NR b R c ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

- C 1-6 alkyl,

- OC 1-6 alkyl,

- OR e ,

-Oaryl,

- Oaryl substituted from 1 to 4 times by R d ,

-Oheteroaryl,

- Oheteroaryl substituted from 1 to 4 times by R d ,

-SH, and

- SR a ; where: e ach R a is independently selected from

C 1-6 alkyl,

R e ,

aryl,

a ryl substituted from 1 to 4 times by R d , heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d ; R b and R c are independently selected from:

C 1-6 alkyl,

R e ,

aryl,

a ryl substituted from 1 to 4 times by R d , heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d ;

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d , or R b and R c are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms independently selected from O, N, and S,, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

- OR e ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d , C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 ,

- N(H)C 1-5 alkyl,

- N(H)R e , - N(C 1-5 alkyl) 2 ,

- NR e R e , -N(R e )C1-5alkyl, -ONHC(NH)NH 2 ,

-Oheterocycloalkyl,

-NHcycloalkyl,

- N(C 1-5 alkyl)cycloalkyl,

-NHheterocycloalkyl,

- N(C 1-5 alkyl)heterocycloalkyl,

- S(O) 2 C 1-4 alkyl,

-SO 2 NH 2

- S(O) 2 phenyl,

benzoyl,

2-methylcyclopropyl,

imidazolyl,

(methoxypyridinylmethyl)amino,

(methylcyclopropylmethyl)amino,

(fluorophenylmethyl)amino,

(methyloxetanylmethyl)amino, and

(methylcyclobutylmethyl)amino, each R d is independently selected from: fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and -CN, cycloalkyl, cycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and -CN, heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and -CN, aryl,

a ryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and -CN,

C1-4alkoxy,

C 1-4 alkoxy substituted from 1 to 4 times by fluoro,

-Oaryl,

- Oaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and -CN,

- OR e ,

-C(O)H,

- C(O)R zz ,

-C(O)aryl,

- C(O)aryl substituted from 1 to 4 times by R zz ,

-C(O)heteroaryl,

- C(O)heteroaryl substituted from 1 to 4 times by R zz , -OC(O)H,

- CO(O)R zz ,

-OC(O)aryl,

- CO(O)aryl substituted from 1 to 4 times by R zz ,

-OC(O)heteroaryl,

- OC(O)heteroaryl substituted from 1 to 4 times by R zz , -SH,

- SR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and -CN,

-S(O)H,

- S(O)R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and -CN,

- S(O) 2 H,

- S(O)2R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and -CN,

- S(O) 2 NH 2 ,

- S(O)2NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and -CN,

- S(O)2NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and -CN,

- P(O)(CH 3 ) 2 ,

-NHS(O)2H,

- NHS(O)2R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and -CN, -NHC(O)H,

- NHC(O)R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and -CN,

- C(O)NH 2 ,

- C(O)NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and -CN,

- C(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

-C(O)OH,

- C(O)OR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and -CN,

oxo,

-OH,

- NH 2 ,

- NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and -CN,

- NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and -CN,

- NH 2 ,

-CN,

- NHC(O)NH 2 ,

- NHC(O)NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–CN, - NHC(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and -CN,

e ach R e is independently selected from:

C 1-6 alkyl substituted with from 1 to 9 substitutents independently selected from:

fluoro,

chloro,

bromo,

iodo,

- OC 1-6 alkyl,

- OC 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and -CN,

- OC(O)C 1-6 alkyl,

- OC(O)C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and -CN,

-ONHC(NH)NH 2 ,

- OP(O)(OH) 2 ,

-SH,

- SR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–CN,

-S(O)H,

- S(O)R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and -CN,

- S(O) 2 H,

- S(O)2R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–CN,

oxo,

-OH,

- NH 2 ,

- NHR xx ,

w here R xx is selected from aryl, heteroaryl, c ycloalkyl, cycloalkyl substituted with C 1-4 alkoxy, C 1-4 alkoxy substituted with from 1 to 6 substituents independently selected from: fluoro, triazolyl, cyclopropyl,oxo, -OR xy , -COOH,–CN, and -NR xy R xz , where R xy and R xz are Independently selected from: h ydrogen, aryl, C 1-5 alkyl heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OR xy , -COOH,–CN, and -NR xy R xz , where R xy and R xz are Independently selected from: hydrogen, aryl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, t riazolyl, cyclopropyl,oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH,

- NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-4 alkoxy, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: f luoro, C 1-4 alkoxy, triazolyl, cyclopropyl, oxo, -OH, - COOH,

- NH 2 , and -CN,

guanidino,

-C(O)OH,

- C(O)OR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–CN,

- C(O)NH 2 ,

- C(O)NHR x ,

w here R x is selected from aryl, heteroaryl, -OH, C1-4alkoxy, cycloalkyl, cycloalkyl substituted with H O-(C 1-4 alkyl)-, heterocyloalkyl, heterocyloalkyl substituted with HO-(C 1-4 alkyl)-, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, heteroaryl, -NH 2 , and–-CN,

- C(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, cycloalkyl substituted w ith HO-(C 1-4 alkyl)-, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–CN,

o r R x1 and R x2 taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms independently selected from O, N, and S, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from fluoro, oxo, -OH, HO- ( C 1-4 alkyl)-, -COOH, -NH 2 , and–CN, aryl, aryl substituted from 1 to 4 times by R x ,

w here R x is selected from fluoro, chloro, bromo, iodo, a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , -N(CH 3 ) 2 , -NHC(O)C 1-4 alkyl, and– CN,

-Oaryl,

- Oaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , -N(CH 3 ) 2 , and -CN,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-4 alkoxy, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–CN,

-Oheteroaryl,

- Oheteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , -N(CH 3 ) 2 , and -CN,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , -N(CH 3 ) 2 , and -CN,

heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from oxo, -OH, -N(C 1-4 alkyl) 2 , aryl, heteroaryl,

c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , -N(CH 3 ) 2 , and -CN,

- S(O) 2 NH 2 ,

- S(O)2NHR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O)2NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 Substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–CN,

- NHS(O) 2 H,

- NHS(O)2R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–CN,

- OC(O)NH 2,

- NHC(O)R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and -CN

- NHC(O)NHR xp ,

w here R xp is selected from heteroaryl, c ycloalkyl, heterocyloalkyl, and C 1-6 alkyl substituted with from 1 to 4 substituents independently selected from: -COOH, -NH 2 , and –-CN,

- NHC(O)NR x3 R x4 ,

w here R x3 and R x4 are each independently selected from heteroaryl, cycloalkyl, heterocyloalkyl, a nd C 1-6 alkyl substituted with from 1 to 6

Substituents independently selected from:

- COOH, -NH 2 , and–-CN,

- NHC(O)C(O)NH 2 ,

- NO 2 , and

-CN; and R z is selected from

C 1-6 alkyl,

R e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d ; R zz is selected from

C 1-6 alkyl, and

R e ; provided that:

X 1br and X 2br are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof. Suitably in the compounds of Formula (Ibr) R 3br is aryl optionally substituted from 1 to 4 times by R d .

Suitably in the compounds of Formula (Ibr) neither X 1br nor X 2br are hydrogen. Suitably in the compounds of Formula (Ibr), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (Ibr), the compounds are in the form of a –C(O)CH(NH 2 )CH(CH 3 ) 2 prodrug. Included in the compounds of the invention and used in the methods of the invention are compounds of Formula (IIbr):

wherein: X 21br and X 22br are independently selected from: hydrogen,

cyano,

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

- OC 1-6 alkyl,

- OR e ,

cycloalkyl,

heterocycloalkyl, and

-SH; Y 1br is selected from: S, NH, and NR z

; R 21br is selected from: amino,

cyano,

fluoro,

chloro,

bromo,

iodo,

C1-6alkyl,

R e ,

- OC 1-6 alkyl, -OR e ,

- NHR a ,

- NR b R c ,

cycloalkyl,

c ycloalkyl substituted with from 1 to 4 times by R d , heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R d , aryl,

a ryl substituted from 1 to 4 times by R d ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d ,

-SH, and

- SR a ; R 23br is selected from: C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, -OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and–-CN, heterocycloalkyl,

aryl,

a ryl substituted from 1 to 4 times by R d ,

heteroaryl, and

h eteroaryl substituted from 1 to 4 times by R d ; and R 25br is selected from: amino,

- NHR a ,

- NR b R c ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

- OC 1-6 alkyl,

- OR e , -Oaryl,

-Oheteroaryl,

-SH, and

- SR a ; where: e ach R a is independently selected from

C 1-6 alkyl,

R e ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d ,

heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d ; R b and R c are independently selected from:

C 1-6 alkyl,

R e ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d ;

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d ,

heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d , or

R b and R c are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo, C 1-6 alkyl,

R e , -OR e ,

aryl,

a ryl substituted from 1 to 4 times by R d , cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d , C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

–-CN,

oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 ,

- N(H)C 1-4 alkyl,

- N(H)R e , -N(C 1-4 alkyl) 2 ,

-ONHC(NH)NH 2 ,

-Oheterocycloalkyl,

-NHcycloalkyl,

-NHheterocycloalkyl,

- S(O) 2 CH 2 CH 3 ,

- S(O) 2 CH 2 CH 2 CH 3 ,

-SO 2 NH 2, -S(O) 2 phenyl,

- S(O) 2 CH 3 ,

benzoyl,

benzylamino,

3-pyrrolidinylpropyl, 2-cyclopropylmethyl, cyclobutylamino, cyclobutyl-N(CH3)-, piperidinyl,

imidazolyl,

morpholinyl,

morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinyl, pyrrolidinyl,

pyrrolidinylmethyl, methoxypyridinylmethylamino, methylpyrrolidinyl, difluoropyrrolidinyl, dimethylpyrrolidinyl, methylcyclopropylmethylamino, hydroxymethylpyrrolidinyl, fluoropyrrolidinyl, fluorophenylmethylamino, piperazinylmethyl, oxazolidinyl,

methyloxetanmethylamino, methylcyclobutylmethylamino, oxoimidazolidinyl, and 2-hydroxyethylpiperidinyl; each R d is independently selected from: fluoro, chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, aryl,

a ryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

C 1-4 alkoxy,

C 1-4 alkoxy substituted from 1 to 4 times by fluoro,

-Oaryl,

- Oaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, -C(O)H,

- C(O)R zz ,

-C(O)aryl,

- C(O)aryl substituted from 1 to 4 times by R zz ,

-C(O)heteroaryl,

- C(O)heteroaryl substituted from 1 to 4 times by R zz , -OC(O)H,

- CO(O)R zz ,

-OC(O)aryl,

- CO(O)aryl substituted from 1 to 4 times by R zz ,

-OC(O)heteroaryl,

- OC(O)heteroaryl substituted from 1 to 4 times by R zz , mercapto,

- SR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

-S(O)H,

- S(O)R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

-S(O)2H,

- S(O)2R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- S(O) 2 NH 2 ,

- S(O)2NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- S(O)2NR x1 R x2 , where R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

- P(O)(CH 3 ) 2 ,

- NHS(O) 2 H,

- NHS(O)2R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–-CN,

-NHC(O)H,

- NHC(O)R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- C(O)NH 2 ,

- C(O)NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- C(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

-C(O)OH,

- C(O)OR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, oxo, hydroxy,

amino,

- NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, - NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

nitro,

cyano,

- NHC(O)NH 2 ,

- NHC(O)NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, - NHC(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

e ach R e is independently selected from:

C 1-6 alkyl substituted with from 1 to 9 substitutents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

- OC 1-6 alkyl,

- OC 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

mercapto,

- SR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

-S(O)H,

- S(O)R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O) 2 H,

- S(O)2R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

oxo,

hydroxy,

amino,

- NHR xx ,

w here R xx is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl,

a nd C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, o xo, -ORxy, -COOH,–-CN, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and –NR xy R xz , where R xy and R xz are independently s elected from: hydrogen, aryl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH,

- NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 Substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

guanidino,

-C(O)OH,

- C(O)OR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- C(O)NH 2 ,

- C(O)NHR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- C(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 Substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

aryl,

a ryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

-Oaryl, -Oaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

-Oheteroaryl,

- Oheteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R x , where R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O) 2 NH 2 ,

- S(O)2NHR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O)2NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 Substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- NHS(O) 2 H,

- NHS(O)2R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- NHC(O)NHR xp ,

w here R xp is selected from heteroaryl, c ycloalkyl, heterocyloalkyl, and C 1-6 alkyl substituted with from 1 to 4 substituents independently selected from: -COOH, -NH 2 , and –-CN,

- NHC(O)NR x3 R x4 ,

w here R x3 and R x4 are each independently selected from heteroaryl, cycloalkyl, heterocyloalkyl, a nd C 1-6 alkyl substituted with from 1 to 6

Substituents independently selected from:

- COOH, -NH 2 , and–-CN,

nitro, and

cyano; and R z is selected from

C 1-6 alkyl,

R e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d ,

heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d ; R zz is selected from

C 1-6 alkyl, and

R e ; provided that: X 21br and X 22br are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof. Suitably in the compounds of Formula (IIbr) R 23br is aryl optionally substituted from 1 to 4 times by R d .

Suitably in the compounds of Formula (IIbr) neither X 21br nor X 22br are hydrogen. Suitably in the compounds of Formula (IIbr), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (IIbr), the compounds are in the form of a –C(O)CH(NH 2 )CH(CH 3 ) 2 prodrug. Included in the compounds of the invention and used in the methods of the invention are compounds of Formula (IIIbr):

r)

wherein:

X 31br and X 32br are independently selected from: hydrogen,

cyano,

fluoro,

chloro,

bromo, iodo,

C 1-6 alkyl,

- OC 1-6 alkyl,

cycloalkyl, and

-SH; Y 2br is selected from: S, NH, and NR z

; R 31br is selected from: C 1-6 alkyl,

R e1 ,

- OC 1-6 alkyl,

- OR e1 ,

- NHR a1 ,

- NR b1 R c1 ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d1 , heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R d1 , aryl,

a ryl substituted from 1 to 4 times by R d1 , heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d1 , -SH, and

- SR a1 ; R 33br is selected from: C 1-6 alkyl,

heterocycloalkyl,

aryl,

a ryl substituted from 1 to 4 times by R d1 , heteroaryl, and

h eteroaryl substituted from 1 to 4 times by R d1 ; and R 35br is selected from: amino, -NHR a1 ,

- NR b1 R c1 ,

aryl,

a ryl substituted from 1 to 4 times by R d1 ,

- OC 1-6 alkyl,

- OR e1 ,

-SH, and

- SR a1 ; where: e ach R a1 is independently selected from

C 1-6 alkyl,

R e1 ,

aryl,

heteroaryl,

cycloalkyl, and

heterocycloalkyl; R b1 and R c1 are independently selected from:

C1-6alkyl,

R e1 ,

- OR e1 ,

aryl,

a ryl substituted from 1 to 4 times by R d1 ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d1 ;

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d1 ,

heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d1 , or R b1 and R c1 are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo, C 1-6 alkyl,

R e1 ,

aryl,

a ryl substituted from 1 to 4 times by R d1 , cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d1 , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d1 , C 1-4 alkoxy, C 1-4 alkoxy substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

–-CN,

oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 ,

- N(H)C 1-4 alkyl,

- N(H)R e1 , -N(C 1-4 alkyl) 2 ,

-ONHC(NH)NH 2 ,

-Oheterocycloalkyl,

-NHcycloalkyl,

-NHheterocycloalkyl,

- S(O) 2 CH 2 CH 3 ,

- S(O) 2 CH 2 CH 2 CH 3 ,

-SO 2 NH 2,

- S(O) 2 phenyl, -S(O) 2 CH 3 ,

benzoyl,

benzylamino,

3-pyrrolidinylpropyl, 2-cyclopropyl methyl, cyclobutylamino, c yclobutyl-N(CH 3 )-, piperidinyl,

imidazolyl,

morpholinyl,

morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinyl, pyrrolidinyl,

pyrrolidinylmethyl, methoxypyridinylmethylamino, methylpyrrolidinyl, difluoropyrrolidinyl, dimethylpyrrolidinyl, methylcyclopropylmethylamino, hydroxymethylpyrrolidinyl, fluoropyrrolidinyl, fluorophenylmethylamino, piperazinylmethyl, oxazolidinyl,

methyloxetanmethylamino, methylcyclobutylmethylamino, oxoimidazolidinyl, and 2-hydroxyethylpiperidinyl; each R d1 is independently selected from: fluoro,

chloro, bromo,

iodo,

C 1-6 alkyl,

R e1 ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

aryl,

a ryl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

C1-4alkoxy,

C 1-4 alkoxy substituted from 1 to 4 times by fluoro,

-Oaryl,

-C(O)H,

- C(O)R zz ,

-C(O)aryl,

-C(O)heteroaryl,

-OC(O)H,

- CO(O)R zz ,

-OC(O)aryl,

-OC(O)heteroaryl,

mercapto,

- SR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

-S(O)H,

- S(O)R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- S(O) 2 H,

- S(O)2R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted from 1 to 6 times by fluoro,

- S(O) 2 NH 2 ,

- S(O)2NHR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

-P(O)(CH3)2,

- NHS(O) 2 H,

- NHS(O)2R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

-NHC(O)H,

- NHC(O)R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- C(O)NH 2 ,

- C(O)NHR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

-C(O)OH,

- C(O)OR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

oxo,

hydroxy,

amino,

- NHR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

nitro,

cyano,

- NHC(O)NH 2 , and

- NHC(O)NHR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro; each R e1 is independently selected from:

C 1-6 alkyl substituted with from 1 to 9 substitutents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

- OC 1-6 alkyl,

- OC 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

mercapto,

- SR xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

-S(O)H,

- S(O)R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro, -S(O) 2 H,

- S(O)2R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro, oxo,

hydroxy,

amino,

- NHR xx ,

w here R xx is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl,

a nd C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, o xo, -ORxy, -COOH,–-CN, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and –NR xy R xz , where R xy and R xz are independently s elected from: hydrogen, aryl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, - OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH,

- NR x1x R x2x ,

w here R x1x and R x2x are each independently s elected from C 1-4 alkyl, and C 1-4 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, and–OH,

guanidino,

-C(O)OH,

- C(O)OR xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- C(O)NHR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, and heterocyloalkyl, aryl,

a ryl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

-Oaryl,

- Oaryl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro, heteroaryl,

h eteroaryl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

-Oheteroaryl,

- Oheteroaryl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted from 1 to 6 times by fluoro, cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R x , where R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O) 2 NH 2 ,

- S(O)2NHR xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- NHS(O) 2 H,

- NHS(O)2R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- NHC(O)NHR xa ,

w here R xa is selected from heteroaryl, cycloalkyl, and heterocyloalkyl,

nitro, and

cyano; and R z is selected from

C 1-6 alkyl,

R e1 ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d1 , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d1 ; R zz is selected from

C 1-6 alkyl, and

R e1 ; provided that:

X 31br and X 32br are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof. Suitably in the compounds of Formula (IIIbr), neither X 31br nor X 32br are hydrogen. Suitably in the compounds of Formula (IIIbr) R 33br is aryl optionally substituted from 1 to 4 times by R d1 . Suitably in the compounds of Formula (IIIbr), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (IIIbr), the compounds are in the form of a –C(O)CH(NH 2 )CH(CH 3 ) 2 prodrug. This invention relates to novel compounds of Formula (IVbbr) and to the use of compounds of Formula (IVbbr) in the methods of the invention:

wherein:

X 41bbr and X 42bbr are independently selected from: --CN, methyl, fluoro, chloro, bromo and iodo; Y 4bbr is selected from: S and NH; R 41bbr is selected from: C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo,

i odo, oxo, C 1-4 alkyloxy, -OH, -COOH, -NH 2 - N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 and -CN,

C 1-4 alkyloxy,

C 1-4 alkyloxy substituted from 1 to 4 times by fluoro, -N(H)C 1-4 alkyl,

- N(C 1-4 alkyl) 2 ,

- SC 1-4 alkyl,

aryl,

aryl substituted with from 1 to 4 substituents

independently selected from: fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–CN,

C 1-4 alkoxy,

–CN,

oxo,

-OH,

-NO 2 , and

-NH 2 ,

heteroaryl,

heteroaryl substituted with from 1 to 4 substituents

independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–CN,

C 1-4 alkoxy,

–CN,

oxo,

-OH,

-NO2, and

-NH 2 , cycloalkyl,

cycloalkyl substituted with from 1 to 4 substituents

independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and -CN,

C 1-4 alkoxy,

-CN,

oxo,

-OH,

-NO 2 , and

-NH 2 ;

R 43bbr is selected from: C 1-4 alkyl,

phenyl,

phenyl substituted with 1 or 2 substituents independently selected from: fluoro, -CH 3 , -CF 3 , chloro, -C(O)phenyl, pyrrolidinyl, - P(O)(CH 3 ) 2 , -C(O)NH 2 , -S(O) 2 NHCH 3 , -OCH 2 CH 2 N(CH 3 ) 2 and –CH 2 C(O)NH 2 ,

thienyl,

piperidinyl,

pyridine, and

pyridine substituted with 1 or 2 substituents independently selected f rom: fluoro, -CH 3 , -CF 3 , and -OCH 3 ; R 44bbr and R 45bbr are independently selected from: hydrogen, C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: phenyl, morpholino, triazolyl, i midazolyl, pyrrolidinyl, -OC(O)NH 2 , -OCH 2 CH 2 NH 2 ,

- ONHC(NH 2 )NH 2 , -NHCH 2 C(CH 3 ) 3 , -NOCH 3 , -NHOH,

- NHCH 2 CH 2 F, -N(CH 3 )CH 2 CH 2 OCH 3 , -N(CH 2 CH 3 ) 2 ,

-NCH(CH2OH)2, -N(CH2CH2OH)2, -NHCH2CH2OH, -NHCH2CH2NH2, -N(CH3)C(CH3)2CH2OH, -NHCH2CH3, - NHCH 2 CH 2 OCH 3 , -N(CH 3 )CH 2 CH 2 OH, -NHC(O)C(O)NH 2 , -N(CH 3 )CH 2 CH 2 CH 2 OH, -N(CH 3 )CH 2 CH(OH)CH 2 OH,

- N(CH 3 )CH 2 CH 2 NH 2 , oxo, -NHCH 2 C(CH 3 ) 2 CH 2 OH, -OH, -NH 2 , -NHCH 3 , -NHCH 2 CH 2 CH 2 OH, -N(CH 3 ) 2 , -N(CH 3 )CH 2 CH 3 , -NHOC(CH 3 ) 2 NH 2 , -N(CH 3 )CH 2 cyclopropyl, -NHCH 2 cyclopropyl, -NHoxetanyl, -NCH 2 CH 2 triazole, piperazinyl, piperidinyl, pyrazolyl, azepinyl, azetidinyl, methoxy, and cyclopropylamino,

where said phenyl, morpholino, triazolyl, imidazolyl, azepinyl, azetidinyl, pyrrolidinyl, piperazinyl, piperidinyl, oxetanyl, cyclopropyl, and pyrazolyl are optionally substituted with from 1 to 4 substituents independently selected from: methyl, fluoro, -NH2, - N(CH 3 ) 2 , hydroxymethyl, oxo, -OH, and–CH 2 NH 2 , cycloalkyl,

cycloalkyl substituted with from one to five substituents

independently selected from:

fluoro,

chloro,

-OH, C 1-6 alkyl, and

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro; heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN, aryl,

C1-4alkoxy, C 1-4 alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

-CN,

oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 , and

SO 2 NH 2, or

R 44bbr and R 45bbr are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms independently selected from O, N, and S, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl-, -OH, -NH 2 , -N(H)C 1-5 alkyl, aminoheterocycloalkyl-, -N(C 1-5 alkyl) 2 , --CN, -N(C 1-4 alkyl)(CH 2 OCH 3 ), and -NHC 1-4 alkyl substituted by one or two substituents independently selected from oxo, NH 2 , and -OH,

aryl,

cycloalkyl,

heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents i ndependently selected from: C 1-6 alkyl, -C 1-6 alkylOH, fluoro, -C 1-6 alkylNH 2 , chloro, bromo, iodo, oxo, -OH, -NH 2 and–CN, C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and -CN,

-CN,

oxo,

-OH,

- OP(O)(OH) 2 , -COOH,

-CONH 2 ,

-NO 2 ,

-NH 2 ,

- N(H)C 1-5 alkyl,

- N(H)C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, bromo, i odo, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, aminoC 1-4 alkoxy, heterocycloalkyl,

m ethylheterocycloalkyl-, -OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and -CN,

-Ooxetanyl,

-ONHC(NH)NH 2 ,

-NHcyclopropyl,

-NHoxetanyl,

- N(C 1-5 alkyl) 2,

- S(O) 2 CH 2 CH 3 ,

S (O) 2 CH 2 CH 2 CH 3 , -S(O) 2 CH 3,

-SO 2 NH 2,

- S(O) 2 phenyl,

benzoyl,

benzylamino,

-propylpyrrolidinyl,

-methylcyclopropyl,

cyclobutylamino,

c yclobutyl-N(CH 3 )-,

piperidinyl, imidazolyl,

morpholinyl,

morpholinylmethyl,

methylpiperazinylmethyl,

methylpiperazinyl,

pyrrolidinyl,

pyrrolidinylmethyl,

(methoxypyridinylmethyl)amino, methylpyrrolidinyl,

difluoropyrrolidinyl,

dimethylpyrrolidinyl,

(methylcyclopropylmethyl)amino, hydroxymethylpyrrolidinyl,

fluoropyrrolidinyl,

fluorophenylmethylamino,

piperazinylmethyl,

oxazolidinyl,

(methyloxetanmethyl)amino,

(methylcyclobutylmethyl)amino, oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl;

provided that: X 41bbr and X 42bbr are not both hydrogen, and R 44bbr and R 45bbr are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (IVbbr) neither R 44bbr nor R 45bbr is hydrogen. Suitably in the compounds of Formula (IVbbr) R 43br is phenyl. Suitably in the compounds of Formula (IVbbr) neither X 41bbr nor X 42bbr are hydrogen. Suitably in the compounds of Formula (IVbbr), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (IVbbr), the compounds are in the form of a –C(O)CH(NH 2 )CH(CH 3 ) 2 prodrug.

This invention relates to novel compounds of Formula (Vbbr) and to the use of compounds of Formula (Vbbr) in the methods of the invention:

wherein:

Y 5bbr is selected from: S and NH; R 50bbr is selected from: C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro, - N(H)C 1-4 alkyl,

- N(C 1-4 alkyl) 2 ,

- SC 1-4 alkyl,

C 1-4 alkyloxy,

aryl,

alkyl substituted with from one to five substituents

independently selected from:

fluoro,

chloro,

-OH, C 1-6 alkyl, and

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro, heteroaryl,

heteroalkyl substituted with from one to five substituents

independently selected from:

fluoro,

chloro,

-OH,

C 1-6 alkyl, and

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro, cycloalkyl,

cycloalkyl substituted with from one to five substituents

independently selected from:

fluoro,

chloro,

-OH,

C 1-6 alkyl, and

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro;

R 51bbr is selected from: - CH 3 ,

phenyl,

phenyl substituted with 1 or 2 substituents independently selected

from: fluoro, -CH 3 , -CF 3 , chloro, -C(O)phenyl, pyrrolidinyl, - C(O)NH 2 , -S(O) 2 NHCH 3 , -OCH 2 CH 2 N(CH 3 ) 2 and -CH 2 C(O)NH 2 , thienyl,

piperidinyl,

pyridine, and pyridine substituted with 1 or 2 substituents independently selected f rom: fluoro, -CH 3 , -CF 3 , and -OCH 3 ; R 53bbr and R 54bbr are independently selected from:

hydrogen,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: phenyl, morpholino, triazolyl, i midazolyl, -CH 2 CH 2 pyrrolidinyl, -OC(O)NH 2 , -OCH 2 CH 2 NH 2 , -ONHC(NH 2 )NH 2 , -NHCH 2 C(CH 3 ) 3 , -NOCH 3 , -NHOH, -NHCH 2 CH 2 F, -N(CH 3 )CH 2 CH 2 OCH 3 , -N(CH 2 CH 3 ) 2 , -NCH(CH 2 OH) 2 , -N(CH 2 CH 2 OH) 2 , -NHCH 2 CH 2 OH, -NHCH 2 CH 2 NH 2 , -N(CH 3 )CH 2 (CH 3 ) 2 CH 2 OH, -NHCH 2 CH 3 , -NHCH 2 CH 2 OCH 3 , -N(CH 3 )CH 2 CH 2 OH, -NHC(O)C(O)NH 2 , -N(CH 3 )CH 2 CH 2 CH 2 OH, -N(CH 3 )CH 2 CH(OH)CH 2 OH, -N(CH 3 )CH 2 CH 2 NH 2 , oxo, -NHCH 2 C(CH 3 ) 2 CH 2 OH, -OH, -NH 2 , -NHCH 3 , -NHCH 2 CH 2 CH 2 OH, -N(CH 3 ) 2 , -N(CH 3 )CH 2 CH 3 , -NHOC(CH 3 ) 2 NH 2 , -N(CH 3 )CH 2 cyclopropyl, -NHCH 2 cyclopropyl, -NHoxetanyl, -NCH 2 CH 2 triazole, piperazinyl, piperidinyl, pyrazolyl, azepinyl, azetidinyl, methoxy, and cyclopropylamino, where said phenyl, morpholino, triazolyl, imidazolyl, azepinyl, azetidinyl, pyrrolidinyl piperazinyl, piperidinyl, oxetanyl, cyclopropyl, and pyrazolyl are optionally substituted with from 1 to 4 substituents independently selected from: methyl, fluoro, -NH 2 , - N(CH 3 ) 2 , hydroxymethyl, oxo, -OH, and -CH 2 NH 2 , cycloalkyl, cycloalkyl substituted with from one to five substituents

independently selected from:

fluoro,

chloro,

-OH,

C 1-6 alkyl, and

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro; heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro, C 1-4 alkoxy, and

-OH, or

R 53bbr and R 54bbr are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms independently

selected from O, N, and S, to form a heterocycloalkyl, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, -OH, -NH 2 , -N(H)C 1-5 alkyl, aminoheterocycloalkyl, -N(C 1-5 alkyl) 2 , -CN, -N(C 1-4 alkyl)(CH 2 OCH 3 ), and -NHC 1-4 alkyl substituted by one or two substituents independently selected from oxo, NH 2 , and -OH,

heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents i ndependently selected from: C 1-6 alkyl,

- C 1-6 alkylOH, fluoro, -C 1-6 alkylNH 2 ,

chloro, oxo and -OH,

C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 4 substituents

Independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and -CN,

-CN,

oxo,

-OH,

- OP(O)(OH) 2 ,

-COOH,

-CONH 2 ,

-NH 2 ,

- N(H)C 1-4 alkyl,

- N(H)C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, aminoC 1-4 alkoxy, heterocycloalkyl,

m ethylheterocycloalkyl, -OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and -CN, -Ooxetanyl,

-ONHC(NH)NH 2 ,

-NHcyclopropyl,

-NHoxetanyl,

- N(C 1-4 alkyl) 2,

- S(O) 2 CH 2 CH 3 ,

S (O) 2 CH 2 CH 2 CH 3 , -S(O) 2 CH 3,

-S(O)2phenyl,

benzoyl,

benzylamino,

-propylpyrrolidinyl,

-methylcyclopropyl, cyclobutylamino,

c yclobutyl-N(CH 3 )-, piperidinyl,

imidazolyl,

morpholinyl,

morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinyll

pyrrolidinyl,

pyrrolidinylmethyl,

(methoxypyridinylmethyl)amino, methylpyrrolidinyl,

difluoropyrrolidinyl, dimethylpyrrolidinyl,

(methylcyclopropylmethyl)amino, hydroxymethylpyrrolidinyl, fluoropyrrolidinyl,

fluorophenylmethylamino, piperazinylmethyl, oxazolidinyl,

(methyloxetanylmethyl)amino,

(methylcyclobutylmethyl)amino, oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl; provided that:

R 53bbr and R 54bbr are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (Vbbr) neither R 53bbr nor R 54bbr is hydrogen. Suitably in the compounds of Formula (Vbbr) R 51bbr is phenyl.

Suitably in the compounds of Formula (Vbbr), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (Vbbr), the compounds are in the form of a –C(O)CH(NH 2 )CH(CH 3 ) 2 prodrug.

This invention relates to novel compounds of Formula (VIbbr) and to the use of compounds of Formula (VIbbr) in the methods of the invention:

wherein:

R 60bbr is selected from: C 1-3 alkyl, C 1-3 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro and chloro, - N(H)C 1-3 alkyl,

- N(C 1-3 alkyl) 2 ,

- SC 1-4 alkyl,

C 1-3 alkyloxy,

aryl,

aryl substituted with from one to 3 substituents

independently selected from:

fluoro,

chloro,

-OH, and

C 1-3 alkyl,

heteroaryl,

heteroaryl substituted with from one to 3 substituents independently selected from:

fluoro,

chloro,

-OH, and

C 1-3 alkyl,

cycloalkyl,

cycloalkyl substituted with from one to three substituents independently selected from:

fluoro,

chloro,

-OH, and

C 1-3 alkyl;

R 61bbr is selected from: - CH 3 ,

phenyl, phenyl substituted with 1 or 2 substituents independently selected from: fluoro, -CH 3 , -CF 3 , chloro, -C(O)phenyl, pyrrolidinyl, - C(O)NH 2 , -S(O) 2 NHCH 3 , -OCH 2 CH 2 N(CH 3 ) 2 and -CH 2 C(O)NH 2 , thienyl,

piperidinyl,

pyridine, and

pyridine substituted with 1 or 2 substituents independently selected

from: fluoro, -CH3, -CF3, and -OCH3;

R 63bbr and R 64bbr are independently selected from:

hydrogen,

C 1-4 alkyl,

C 1-4 alkyl substituted with from 1 to 4 substituents

independently selected from: phenyl, morpholino, triazolyl, i midazolyl, -CH 2 CH 2 pyrrolidinyl, -OC(O)NH 2 , -OCH 2 CH 2 NH 2 , -ONHC(NH 2 )NH 2 , -NHCH 2 C(CH 3 ) 3 , -NOCH 3 , -NHOH, -NHCH 2 CH 2 F, -N(CH 3 )CH 2 CH 2 OCH 3 , -N(CH 2 CH 3 ) 2 , -NCH(CH 2 OH) 2 , -N(CH 2 CH 2 OH) 2 , -NHCH 2 CH 2 OH, -NHCH 2 CH 2 NH 2 , -N(CH 3 )CH 2 (CH 3 ) 2 CH 2 OH, -NHCH 2 CH 3 , -NHCH 2 CH 2 OCH 3 , -N(CH 3 )CH 2 CH 2 OH, -NHC(O)C(O)NH 2 , -N(CH 3 )CH 2 CH 2 CH 2 OH, -N(CH 3 )CH 2 CH(OH)CH 2 OH, -N(CH 3 )CH 2 CH 2 NH 2 , oxo, -NHCH 2 C(CH 3 ) 2 CH 2 OH, -OH, -NH 2 , -NHCH 3 , -NHCH 2 CH 2 CH 2 OH, -N(CH 3 ) 2 , -N(CH 3 )CH 2 CH 3 , -NHOC(CH 3 ) 2 NH 2 , -N(CH 3 )CH 2 cyclopropyl, -NHCH 2 cyclopropyl, -NHoxetanyl, -NCH 2 CH 2 triazole, piperazinyl, piperidinyl, pyrazolyl, azepinyl, azetidinyl, methoxy, and cyclopropylamino, where said phenyl, morpholino, triazolyl, imidazolyl, azepinyl, azetidinyl, pyrrolidinyl piperazinyl, piperidinyl, oxetanyl, cyclopropyl, and pyrazolyl are optionally substituted with from 1 to 4 substituents independently selected from: methyl, fluoro, -NH 2 , - N(CH 3 ) 2 , hydroxymethyl, oxo, -OH, and -CH 2 NH 2 , cycloalkyl,

cycloalkyl substituted with from 1 to 5 substituents independently

selected from:

fluoro,

chloro,

-OH, and

C 1-6 alkyl,

heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

-OH, and

C 1-6 alkyl, or

R 63bbr and R 64bbr are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms independently

selected from O, N, and S, to form a heterocycloalkyl, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

-OH,

- OP(O)(OH) 2 ,

-CN,

C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, -OH, -NH 2 , -N(H)C 1-5 alkyl, aminoheterocycloalkyl, -N(C 1-5 alkyl) 2 , -CN, -N(C 1-4 alkyl)(CH 2 OCH 3 ), and -NHC 1-4 alkyl substituted by one or two substituents independently selected from oxo, NH 2 , and -OH,

heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents i ndependently selected from: C 1-6 alkyl,

- C 1-6 alkylOH, fluoro, chloro, oxo and -OH, C 1-4 alkoxy,

C1-4alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and -CN,

oxo,

- NH 2 , -N(H)C 1-6 alkyl,

- N(H)C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl,

a minoC 1-4 alkoxy, heterocycloalkyl,

m ethylheterocycloalkyl, -OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and -CN,

- ONHC(NH)NH 2 ,

-Ooxetanyl, -ONHC(NH)NH 2 ,

-NHcyclopropyl,

-NHoxetanyl,

- N(C 1-4 alkyl) 2,

- S(O) 2 CH 2 CH 3 ,

S (O) 2 CH 2 CH 2 CH 3 ,

- S(O) 2 CH 3,

- S(O) 2 phenyl,

benzoyl,

benzylamino,

-propylpyrrolidinyl,

-methylcyclopropyl, cyclobutylamino,

c yclobutyl-N(CH 3 )-, piperidinyl,

imidazolyl,

morpholinyl,

morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinyl,

pyrrolidinyl,

pyrrolidinylmethyl,

(methoxypyridinylmethyl)amino, methylpyrrolidinyl,

difluoropyrrolidinyl, dimethylpyrrolidinyl,

(methylcyclopropylmethyl)amino, hydroxymethylpyrrolidinyl, fluoropyrrolidinyl,

(fluorophenylmethyl)amino, piperazinylmethyl,

oxazolidinyl, (methyloxetanylmethyl)amino,

(methylcyclobutylmethyl)amino, oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl;

provided that: R 63bbr and R 64bbr are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (VIbbr) neither R 63bbr nor R 64bbr is hydrogen. Suitably in the compounds of Formula (VIbbr) R 61bbr is phenyl.

Suitably in the compounds of Formula (VIbbr), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (VIbbr), the compounds are in the form of a –C(O)CH(NH 2 )CH(CH 3 ) 2 prodrug.

This invention relates to novel compounds of Formula (VIIbbr) and to the use of compounds of Formula (VIIbbr) in the methods of the invention:

wherein: R 70bbr is selected from:

ethyl,

ethyl substituted from 1 to 4 times by fluoro,

- NCH 3 , -SCH 3 ,

ethoxy,

methoxy,

propoxy,

phenyl,

furanyl,

cyclopropyl, and

cyclopropyl substituted once or twice by fluoro;

R 71bbr is selected from:

phenyl,

phenyl substituted with 1 or 2 substituents independently selected

from: fluoro, -CH 3 , -CF 3 , chloro, -C(O)phenyl, pyrrolidinyl, - C(O)NH 2 , -S(O) 2 NHCH 3 , -OCH 2 CH 2 N(CH 3 ) 2 and–CH 2 C(O)NH 2 , thienyl,

piperidinyl,

pyridine, and

pyridine substituted with 1 or 2 substituents independently selected

f rom: fluoro, -CH 3 , -CF 3 , and -OCH 3 ; and

R 72bbr and R 73bbr are independently selected from:

hydrogen,

C 1-4 alkyl,

C 1-4 alkyl substituted with from 1 to 4 substituents

independently selected from: phenyl, morpholino, triazolyl, i midazolyl, -CH 2 CH 2 pyrrolidinyl, -OC(O)NH 2 , -OCH 2 CH 2 NH 2 , -ONHC(NH 2 )NH 2 , -NHCH 2 C(CH 3 ) 3 , -NOCH 3 , -NHOH, -NHCH 2 CH 2 F, -N(CH 3 )CH 2 CH 2 OCH 3 , -N(CH 2 CH 3 ) 2 , -NCH(CH2OH)2, -N(CH2CH2OH)2, -NHCH2CH2OH, -NHCH2CH2NH2, -N(CH3)CH2(CH3)2CH2OH, -NHCH2CH3, -NHCH 2 CH 2 OCH 3 , -N(CH 3 )CH 2 CH 2 OH, -NHC(O)C(O)NH 2 , -N(CH 3 )CH 2 CH 2 CH 2 OH, -N(CH 3 )CH 2 CH(OH)CH 2 OH, -N(CH 3 )CH 2 CH 2 NH 2 , oxo, -NHCH 2 C(CH 3 ) 2 CH 2 OH, -OH, -NH 2 , -NHCH 3 , -NHCH 2 CH 2 CH 2 OH, -N(CH 3 ) 2 , -N(CH 3 )CH 2 CH 3 , -NHOC(CH 3 ) 2 NH 2 , -N(CH 3 )CH 2 cyclopropyl, -NHCH 2 cyclopropyl, -NHoxetanyl, -NCH 2 CH 2 triazole, piperazinyl, piperidinyl, pyrazolyl, azepinyl, azetidinyl, methoxy, and cyclopropylamino,

where said phenyl, morpholino, triazolyl, imidazolyl, azepinyl, azetidinyl, pyrrolidinyl piperazinyl, piperidinyl, oxetanyl, cyclopropyl, and pyrazolyl are optionally substituted with from 1 to 4 substituents independently selected from: methyl, fluoro, -NH 2 , - N(CH 3 ) 2 , hydroxymethyl, oxo, -OH, and–CH 2 NH 2 , cyclobutyl,

aminocyclobutyl,

tetrahydrofuran,

5-oxa-2azaspiro[3.4]octan, and

8-azabicyclo[3.2.1]octan, or

R 72bbr and R 73bbr are taken together with the nitrogen to which they are

attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl selected from:

pyrrolidinyl,

pyrrolo[3,4-c]pyrazolyl,

piperidinyl,

1,4diazepanyl,

piperazinyl,

6,7-dihydro-triazolo[4,5-c]pyridinyl,

2,9-diazaspiro[5.5]undecanyl,

2,8-diazaspiro[4.5]decanyl,

octahydro-1H-pyrrolo[1,2a][1,4]diazepinyl, oxa-diazaspiro[4.5]decanyl, oxazolyl,

morpholinyl,

1-oxa-6-azaspiro[3.4]octanyl,

2-oxa-6-azaspiro[3.4]octanyl,

1,7-diazaspiro[3.5]nonanyl,

2,7-diazaspiro[3.5]nonanyl,

2,6-diazaspiro[3.4]octanyl,

azetidinyl,

hexahydropyrrolo[3,4-b]oxazinyl,

dihydronaphthyridinyl,

diazabicycloheptanyl,

1,8-diazaspiro[4.5]decanyl, and

5-oxa-2-azaspiro[3.4]octanyl,

all of which are optionally substituted with from 1 to 5 substituents independently selected from: fluoro,

chloro,

oxo,

-OH,

--CN,

- CH 3 ,

- CH 2 OH,

methoxy,

- CH 2 CH 3 ,

- C(O)CH 3 ,

- C(O)NH 2 ,

- OCH 2 CH 2 OH,

- OCH 2 CH 2 NH 2 ,

- ONHC(NH)NH 2 ,

- OC(O)NH 2 ,

-Ooxetanyl, -CH 2 CH 2 OH,

- CH 2 CH 2 CH 2 OH, -CH 2 CH 2 CH 3 ,

- CH 2 CH 2 OCH 3 ,

- CH 2 CH(OH)CH 3 , -CH 2 CH(OH)CH 2 OH, -CH 2 C(O)OCH 3 ,

- CH 2 C(O)NH 2 ,

- C(O)CH(CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 NHCH 2 CH 3 , -CH 2 CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 NHCH 2 C(CH 3 ) 3 , -CH 2 CH 2 N(CH 3 )CH 2 OCH 3 , -C(CH 3 ) 2 CH 2 OH, -CH 2 C(CH 3 ) 2 OH, -CH 2 C(CH 3 ) 2 OCH 3 , -C(O)CH 2 OH,

- CH 2 isothiazolyl,

- CH 2 thiazolyl,

- CH 2 pyrazolyl,

- CH 2 imidazolyl,

- CH 2 pyridinyl,

-CH2oxazolyl, -CH 2 pyrrolyl,

- CH 2 isoxazoly, -CH 2 furanyl,

- CH 2 CH 2morpholinyl , -CH 2 CH 2 pyrrolidinyl, -CH 2 CH 2 pyrrolidinylCH 3 , -CH 2 CH 2 CH 2 pyrrolidinyl, -C(O)phenyl,

-C(O)C(tetrahydropyranyl)NH 2 , -NH 2 ,

- NHCH 3 ,

- N(CH 3 ) 2 , -NHC(O)CH 3 ,

- NHCH 2 CHF 2 ,

- NHCH 2 C(CH 3)3 ,

- NHCH 2 CH(CH 3)2 ,

- NHCH 2 CH 2 OCH 3 , -NHCH 2 CH 2 OH,

- NHCH 2 CH 2 NH 2 ,

- NHCH 2 C(O)OH,

- NHC(O)CH 2 NH 2 ,

- NHC(O)CH 2 CH 2 CH 2 NH 2 , -NHCH 2 C(O)NH 2 ,

- NHCH 2 C(OH)(CH 3 ) 2 , -NHC(O)CH(CH 3 )NH 2 , -NHC(O)OCH(CH 3 )NH 2 , -NHC(O)CH(CH 3 ) 2 , -NHC(O)C(CH 3 ) 2 NH 2 , -NHC(O)CH 2 OH, -NHC(O)CH(CH 2 OH)NH 2 , -NHC(O)(oxetanyl)NH 2 , -NHC(O)OC(CH 3 ) 3 , -NHC(CH 3 ) 2 C(O)OCH 3 , -NHcyclopropyl, -NHoxetanyl,

- CH 2 NH 2 ,

- CH 2 CH 2 NH 2 ,

- CH 2 CH 2 CH 2 NH 2 , -CH 2 NHCH 2 C(CH 3 ) 3 , -CH 2 NHC(O)C(CH 3 ) 3 , -CH 2 NHC(O)CH 2 NH 2 , -CH 2 NHC(O)CH 2 OH, -CH 2 N(CH 3 ) 2 ,

- CH 2 NHCH 3 ,

- CH 2 N(CH 2 CH 3 ) 2 , -CH 2 CH 2 N(CH 3 ) 2 , -S(O) 2 CH 2 CH 3 , -S(O) 2 CH 2 CH 2 CH 3 , -S(O) 2 phenyl, -S(O) 2 CH 3 ,

benzoyl,

benzylamino,

3-pyrrolidinylpropyl,

2-cyclopropylmethyl, cyclobutylamino, c yclobutyl-N(CH 3 )-, piperidinyl,

imidazolyl,

morpholinyl,

morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinyl, pyrrolidinyl,

pyrrolidinylmethyl, methoxypyridinylmethylamino, methylpyrrolidinyl, difluoropyrrolidinyl, dimethylpyrrolidinyl, methylcyclopropylmethylamino, hydroxymethylpyrrolidinyl, fluoropyrrolidinyl, fluorophenylmethylamino, piperazinylmethyl, oxazolidinyl,

methyloxetanmethylamino, methylcyclobutylmethylamino, oxoimidazolidinyl, and 2-hydroxyethylpiperidinyl; provided that:

R 72bbr and R 73bbr are not both hydrogen, or a pharmaceutically acceptable salt or prodrug thereof. Suitably in the compounds of Formula (VIIbbr) neither R 72bbr nor R 73bbr is hydrogen. Suitably in the compounds of Formula (VIIbbr) R 71bbr is phenyl.

Suitably in the compounds of Formula (VIIbbr), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (VIIbbr), the compounds are in the form of a –C(O)CH(NH 2 )CH(CH 3 ) 2 prodrug.

This invention relates to novel compounds of Formula (Qb) and to the use of compounds of Formula (Qb) in the methods of the invention:

wherein:

R 70a’’ is selected from:

ethyl,

-OCH 3 ,

-CH 2 CF 3 , and

cyclopropyl;

R 71a’’ is selected from:

phenyl,

phenyl substituted with 1 or 2 substituents independently selected

from: fluoro, -CH 3 , -CF 3 , and chloro,

pyridine, and

pyridine substituted with 1 or 2 substituents independently selected

f rom: fluoro, -CH 3 , -CF 3 , and -OCH 3 ; and R 72a and R 73a are independently selected from:

hydrogen,

C 1-4 alkyl,

C 1-4 alkyl substituted with from 1 to 4 substituents

independently selected from: phenyl, morpholino, triazolyl, i midazolyl, -CH 2 CH 2 pyrrolidinyl, -OC(O)NH 2 , -OCH 2 CH 2 NH 2 , -ONHC(NH 2 )NH 2 , -NHCH 2 C(CH 3 ) 3 , -NOCH 3 , -NHOH, -NHCH 2 CH 2 F, -N(CH 3 )CH 2 CH 2 OCH 3 , -N(CH 2 CH 3 ) 2 , -NCH(CH 2 OH) 2 , -N(CH 2 CH 2 OH) 2 , -NHCH 2 CH 2 OH, -NHCH 2 CH 2 NH 2 , -N(CH 3 )CH 2 (CH 3 ) 2 CH 2 OH, -NHCH 2 CH 3 , -NHCH 2 CH 2 OCH 3 , -N(CH 3 )CH 2 CH 2 OH, -NHC(O)C(O)NH 2 , -N(CH 3 )CH 2 CH 2 CH 2 OH, -N(CH 3 )CH 2 CH(OH)CH 2 OH, -N(CH 3 )CH 2 CH 2 NH 2 , oxo, -NHCH 2 C(CH 3 ) 2 CH 2 OH, -OH, -NH 2 , -NHCH 3 , -NHCH 2 CH 2 CH 2 OH, -N(CH 3 ) 2 , -N(CH 3 )CH 2 CH 3 , -NHOC(CH 3 ) 2 NH 2 , -N(CH 3 )CH 2 cyclopropyl, -NHCH 2 cyclopropyl, -NHoxetanyl, -NCH 2 CH 2 triazole, piperazinyl, piperidinyl, pyrazolyl, azepinyl, azetidinyl, methoxy, and cyclopropylamino, where said phenyl, morpholino, triazolyl, imidazolyl, azepinyl, azetidinyl, pyrrolidinyl piperazinyl, piperidinyl, oxetanyl, cyclopropyl, and pyrazolyl are optionally substituted with from 1 to 4 substituents independently selected from: methyl, fluoro, -NH 2 , - N(CH 3 ) 2 , hydroxymethyl, oxo, -OH, and -CH 2 NH 2 , cyclobutyl,

aminocyclobutyl,

tetrahydrofuran,

5-oxa-2azaspiro[3.4]octan, and 8-azabicyclo[3.2.1]octan, or

R 72a’’ and R 73a’’ are taken together with the nitrogen to which they are

attached, and optionally from 1 to 3 additional heteroatoms independently

selected from O, N, and S, to form a heterocycloalkyl selected from: pyrrolidinyl,

pyrrolo[3,4-c]pyrazolyl,

piperidinyl,

1,4diazepanyl,

piperazinyl,

6,7-dihydro-triazolo[4,5-c]pyridinyl,

2,9-diazaspiro[5.5]undecanyl,

2,8-diazaspiro[4.5]decanyl,

octahydro-1H-pyrrolo[1,2a][1,4]diazepinyl, oxa-diazaspiro[4.5]decanyl,

oxazolyl,

morpholinyl,

1-oxa-6-azaspiro[3.4]octanyl,

2-oxa-6-azaspiro[3.4]octanyl,

1,7-diazaspiro[3.5]nonanyl,

2,7-diazaspiro[3.5]nonanyl,

2,6-diazaspiro[3.4]octanyl,

azetidinyl,

hexahydropyrrolo[3,4-b]oxazinyl,

dihydronaphthyridinyl,

diazabicycloheptanyl,

1,8-diazaspiro[4.5]decanyl, and

5-oxa-2-azaspiro[3.4]octanyl,

all of which are optionally substituted with from 1 to 5

substituents independently selected from:

fluoro,

chloro,

oxo,

-OH, -OP(O)(OH) 2 , -CN,

- CH 3 ,

- CH 2 OH, methoxy,

- CH 2 CH 3 ,

- C(O)CH 3 ,

- C(O)NH 2 ,

- OCH 2 CH 2 OH, -OCH 2 CH 2 NH 2 , -ONHC(NH)NH 2 , -OC(O)NH 2 ,

-Ooxetanyl,

- CH 2 CH 2 OH, -CH2CH2CH2OH, -CH2CH2CH3, -CH 2 CH 2 OCH 3 , -CH 2 CH(OH)CH 3 , -CH 2 CH(OH)CH 2 OH, -CH 2 C(O)OCH 3 , -CH 2 C(O)NH 2 , -C(O)CH(CH 3 ) 2 , -CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 NHCH 2 CH 3 , -CH 2 CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 NHCH 2 C(CH 3 ) 3 , -CH 2 CH 2 N(CH 3 )CH 2 OCH 3 , -C(CH 3 ) 2 CH 2 OH,

- CH 2 C(CH 3 ) 2 OH,

- CH 2 C(CH 3 ) 2 OCH 3 , -C(O)CH 2 OH,

- CH 2 isothiazolyl,

- CH 2 thiazolyl,

- CH 2 pyrazolyl,

- CH 2 imidazolyl,

- CH 2 pyridinyl,

- CH 2 oxazolyl, -CH 2 pyrrolyl,

- CH 2 isoxazoly,

- CH 2 furanyl,

- CH 2 CH 2morpholinyl , -CH 2 CH 2 pyrrolidinyl, -CH 2 CH 2 pyrrolidinylCH 3 , -CH 2 CH 2 CH 2 pyrrolidinyl, -C(O)phenyl,

-C(O)C(tetrahydropyranyl)NH 2 , -NH 2 ,

- NHCH 3 ,

- N(CH 3 ) 2 , -NHC(O)CH 3 ,

- NHCH 2 CHF 2 , -NHCH 2 C(CH 3)3 , -NHCH 2 CH(CH 3)2 , -NHCH 2 CH 2 OCH 3 , -NHCH 2 CH 2 OH, -NHCH 2 CH 2 NH 2 , -NHCH 2 C(O)OH, -NHC(O)CH 2 NH 2 , -NHC(O)CH 2 CH 2 CH 2 NH 2 , -NHCH 2 C(O)NH 2 , -NHCH 2 C(OH)(CH 3 ) 2 , -NHC(O)CH(CH 3 )NH 2 , -NHC(O)OCH(CH 3 )NH 2 , -NHC(O)CH(CH 3 ) 2 , -NHC(O)C(CH 3 ) 2 NH 2 , -NHC(O)CH 2 OH, -NHC(O)CH(CH 2 OH)NH 2 , -NHC(O)(oxetanyl)NH 2 , -NHC(O)OC(CH 3 ) 3 , -NHC(CH 3 ) 2 C(O)OCH 3 , -NHcyclopropyl,

-NHoxetanyl,

- CH 2 NH 2 ,

- CH 2 CH 2 NH 2 , -CH 2 CH 2 CH 2 NH 2 ,

- CH 2 NHCH 2 C(CH 3 ) 3 , -CH 2 NHC(O)C(CH 3 ) 3 , -CH 2 NHC(O)CH 2 NH 2 , -CH 2 NHC(O)CH 2 OH, -CH 2 N(CH 3 ) 2 ,

- CH 2 NHCH 3 ,

- CH 2 N(CH 2 CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 ,

- S(O) 2 CH 2 CH 3 ,

- S(O) 2 CH 2 CH 2 CH 3 , -S(O) 2 phenyl, -S(O) 2 CH 3 ,

benzoyl,

benzylamino,

-propylpyrrolidinyl,

-methylcyclopropyl, cyclobutylamino,

c yclobutyl-N(CH 3 )-, piperidinyl,

imidazolyl,

morpholinyl,

morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinyl, pyrrolidinyl,

pyrrolidinylmethyl,

(methoxypyridinylmethyl)amino, methylpyrrolidinyl,

difluoropyrrolidinyl,

dimethylpyrrolidinyl,

(methylcyclopropylmethyl)amino,

hydroxymethylpyrrolidinyl,

fluoropyrrolidinyl,

(fluorophenylmethyl)amino,

piperazinylmethyl,

oxazolidinyl,

(methyloxetanylmethyl)amino,

(methylcyclobutylmethyl)amino,

oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl;

provided that:

R 72a’’ and R 73a’’ are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (Qb) neither R 72a’’ nor R 73a’’ is hydrogen. Suitably in the compounds of Formula (Qb) R 71a” is phenyl.

Suitably in the compounds of Formula (Qb), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (Qb), the compounds are in the form of a –C(O)CH(NH 2 )CH(CH 3 ) 2 prodrug.

This invention relates to novel compounds of Formula (Qb1) and to the use of compounds of Formula (Qb1) in the methods of the invention: (Qb1)

wherein: R 70b’’ is selected from:

ethyl,

-OCH 3 ,

-CH 2 CF 3 , and

cyclopropyl;

R 71b’’ is selected from:

phenyl,

phenyl substituted with 1 or 2 substituents independently selected from: fluoro, -CH 3 , -CF 3 , and chloro,

pyridine, and

pyridine substituted with 1 or 2 substituents independently selected f rom: fluoro, -CH 3 , -CF 3 , and -OCH 3 ; and R 72b’’ and R 73b’’ are independently selected from: C 1-4 alkyl,

C 1-4 alkyl substituted with from 1 to 4 substituents

independently selected from: phenyl, morpholino, triazolyl, i midazolyl, -CH 2 CH 2 pyrrolidinyl, -OC(O)NH 2 , -OCH 2 CH 2 NH 2 , -ONHC(NH 2 )NH 2 , -NHCH 2 C(CH 3 ) 3 , -NOCH 3 , -NHOH, -NHCH 2 CH 2 F, -N(CH 3 )CH 2 CH 2 OCH 3 , -N(CH 2 CH 3 ) 2 , -NCH(CH 2 OH) 2 , -N(CH 2 CH 2 OH) 2 , -NHCH 2 CH 2 OH, -NHCH 2 CH 2 NH 2 , -N(CH 3 )CH 2 (CH 3 ) 2 CH 2 OH, -NHCH 2 CH 3 , -NHCH 2 CH 2 OCH 3 , -N(CH 3 )CH 2 CH 2 OH, -NHC(O)C(O)NH 2 , -N(CH 3 )CH 2 CH 2 CH 2 OH, -N(CH 3 )CH 2 CH(OH)CH 2 OH,

- N(CH 3 )CH 2 CH 2 NH 2 , oxo, -NHCH 2 C(CH 3 ) 2 CH 2 OH, -OH, -NH 2 , -NHCH 3 , -NHCH 2 CH 2 CH 2 OH, -N(CH 3 ) 2 , -N(CH 3 )CH 2 CH 3 , -NHOC(CH 3 ) 2 NH 2 , -N(CH 3 )CH 2 cyclopropyl, -NHCH 2 cyclopropyl, -NHoxetanyl, -NCH 2 CH 2 triazole, piperazinyl, piperidinyl, pyrazolyl, azepinyl, azetidinyl, methoxy, and cyclopropylamino,

where said phenyl, morpholino, triazolyl, imidazolyl, azepinyl, azetidinyl, pyrrolidinyl piperazinyl, piperidinyl, oxetanyl, cyclopropyl, and pyrazolyl are optionally substituted with from 1 to 4 substituents independently selected from: methyl, fluoro, -NH 2 , - N(CH 3 ) 2 , hydroxymethyl, oxo, -OH, and–CH 2 NH 2 , cyclobutyl,

aminocyclobutyl,

tetrahydrofuran,

5-oxa-2azaspiro[3.4]octan, and

8-azabicyclo[3.2.1]octan, or

R 72b’’ and R 73b’’ are taken together with the nitrogen to which they are

attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl selected from:

pyrrolidinyl,

pyrrolo[3,4-c]pyrazolyl,

piperidinyl,

1,4diazepanyl,

piperazinyl,

6,7-dihydro-triazolo[4,5-c]pyridinyl,

2,9-diazaspiro[5.5]undecanyl,

2,8-diazaspiro[4.5]decanyl,

octahydro-1H-pyrrolo[1,2a][1,4]diazepinyl, oxa-diazaspiro[4.5]decanyl,

oxazolyl, morpholinyl,

1-oxa-6-azaspiro[3.4]octanyl,

2-oxa-6-azaspiro[3.4]octanyl,

1,7-diazaspiro[3.5]nonanyl,

2,7-diazaspiro[3.5]nonanyl,

2,6-diazaspiro[3.4]octanyl,

azetidinyl,

hexahydropyrrolo[3,4-b]oxazinyl,

dihydronaphthyridinyl,

diazabicycloheptanyl,

1,8-diazaspiro[4.5]decanyl, and

5-oxa-2-azaspiro[3.4]octanyl,

all of which are optionally substituted with from 1 to 5 substituents independently selected from: fluoro,

chloro,

oxo,

-OH,

--CN,

-CH3,

-CH2OH,

methoxy,

- CH 2 CH 3 ,

- C(O)CH 3 ,

- C(O)NH 2 , -OCH 2 CH 2 OH,

- OCH 2 CH 2 NH 2 ,

- ONHC(NH)NH 2 ,

- OC(O)NH 2 ,

-Ooxetanyl, -CH 2 CH 2 OH,

- CH 2 CH 2 CH 2 OH, -CH 2 CH 2 CH 3 ,

- CH 2 CH 2 OCH 3 ,

- CH 2 CH(OH)CH 3 , -CH 2 CH(OH)CH 2 OH, -CH 2 C(O)OCH 3 ,

- CH 2 C(O)NH 2 ,

- C(O)CH(CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 NHCH 2 CH 3 , -CH 2 CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 NHCH 2 C(CH 3 ) 3 , -CH 2 CH 2 N(CH 3 )CH 2 OCH 3 , -C(CH 3 ) 2 CH 2 OH, -CH 2 C(CH 3 ) 2 OH, -CH 2 C(CH 3 ) 2 OCH 3 , -C(O)CH 2 OH,

- CH 2 isothiazolyl,

- CH 2 thiazolyl,

- CH 2 pyrazolyl,

- CH 2 imidazolyl,

- CH 2 pyridinyl,

-CH2oxazolyl, -CH 2 pyrrolyl,

- CH 2 isoxazoly, -CH 2 furanyl,

- CH 2 CH 2morpholinyl , -CH 2 CH 2 pyrrolidinyl, -CH 2 CH 2 pyrrolidinylCH 3 , -CH 2 CH 2 CH 2 pyrrolidinyl, -C(O)phenyl,

-C(O)C(tetrahydropyranyl)NH 2 , -NH 2 ,

- NHCH 3 ,

- N(CH 3 ) 2 , -NHC(O)CH 3 ,

- NHCH 2 CHF 2 ,

- NHCH 2 C(CH 3)3 ,

- NHCH 2 CH(CH 3)2 ,

- NHCH 2 CH 2 OCH 3 , -NHCH 2 CH 2 OH,

- NHCH 2 CH 2 NH 2 ,

- NHCH 2 C(O)OH,

- NHC(O)CH 2 NH 2 ,

- NHC(O)CH 2 CH 2 CH 2 NH 2 , -NHCH 2 C(O)NH 2 ,

- NHCH 2 C(OH)(CH 3 ) 2 , -NHC(O)CH(CH 3 )NH 2 , -NHC(O)OCH(CH 3 )NH 2 , -NHC(O)CH(CH 3 ) 2 , -NHC(O)C(CH 3 ) 2 NH 2 , -NHC(O)CH 2 OH, -NHC(O)CH(CH 2 OH)NH 2 , -NHC(O)(oxetanyl)NH 2 , -NHC(O)OC(CH 3 ) 3 , -NHC(CH 3 ) 2 C(O)OCH 3 , -NHcyclopropyl, -NHoxetanyl,

- CH 2 NH 2 ,

- CH 2 CH 2 NH 2 ,

- CH 2 CH 2 CH 2 NH 2 , -CH 2 NHCH 2 C(CH 3 ) 3 , -CH 2 NHC(O)C(CH 3 ) 3 , -CH 2 NHC(O)CH 2 NH 2 , -CH 2 NHC(O)CH 2 OH, -CH 2 N(CH 3 ) 2 ,

- CH 2 NHCH 3 ,

- CH 2 N(CH 2 CH 3 ) 2 , -CH 2 CH 2 N(CH 3 ) 2 , -S(O) 2 CH 2 CH 3 , -S(O) 2 CH 2 CH 2 CH 3 , -S(O) 2 phenyl, -S(O) 2 CH 3 ,

benzoyl,

benzylamino,

3-pyrrolidinylpropyl,

2-cyclopropylmethyl, cyclobutylamino, c yclobutyl-N(CH 3 )-, piperidinyl,

imidazolyl,

morpholinyl,

morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinyl, pyrrolidinyl,

pyrrolidinylmethyl, methoxypyridinylmethylamino, methylpyrrolidinyl, difluoropyrrolidinyl, dimethylpyrrolidinyl, methylcyclopropylmethylamino, hydroxymethylpyrrolidinyl, fluoropyrrolidinyl, fluorophenylmethylamino, piperazinylmethyl, oxazolidinyl,

methyloxetanmethylamino, methylcyclobutylmethylamino, oxoimidazolidinyl, and 2-hydroxyethylpiperidinyl; provided that:

R 72b’’ and R 73b’’ are not both unsubstituted alkyl; or a pharmaceutically acceptable salt or prodrug thereof. Suitably in the compounds of Formula (Qb1) R 71b” is phenyl.

Suitably in the compounds of Formula (Qb1), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (Qb1), the compounds are in the form of a –C(O)CH(NH 2 )CH(CH 3 ) 2 prodrug.

This invention relates to novel compounds of Formula (Qb2) and to the use of compounds of Formula (Qb2) in the methods of the invention:

wherein: R 70c’’ is selected from:

ethyl,

-OCH 3 ,

-CH 2 CF 3 , and

cyclopropyl;

R 71c’’ is selected from:

phenyl,

phenyl substituted with 1 or 2 substituents independently selected

from: fluoro, -CH 3 , -CF 3 , and chloro,

pyridine, and

pyridine substituted with 1 or 2 substituents independently selected

f rom: fluoro, -CH 3 , -CF 3 , and -OCH 3 ; and

R 72c’’ and R 73c’’ are are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl selected from:

pyrrolidinyl,

pyrrolo[3,4-c]pyrazolyl,

piperidinyl,

1,4diazepanyl,

piperazinyl,

6,7-dihydro-triazolo[4,5-c]pyridinyl,

2,9-diazaspiro[5.5]undecanyl,

2,8-diazaspiro[4.5]decanyl,

octahydro-1H-pyrrolo[1,2a][1,4]diazepinyl, oxa-diazaspiro[4.5]decanyl,

oxazolyl,

morpholinyl,

1-oxa-6-azaspiro[3.4]octanyl,

2-oxa-6-azaspiro[3.4]octanyl,

1,7-diazaspiro[3.5]nonanyl,

2,7-diazaspiro[3.5]nonanyl,

2,6-diazaspiro[3.4]octanyl,

azetidinyl,

hexahydropyrrolo[3,4-b]oxazinyl,

dihydronaphthyridinyl,

diazabicycloheptanyl,

1,8-diazaspiro[4.5]decanyl, and

5-oxa-2-azaspiro[3.4]octanyl,

all of which are optionally substituted with from 1 to 5 substituents independently selected from: fluoro,

chloro,

oxo,

-OH,

--CN,

- CH 3 ,

-CH2OH, methoxy,

- CH 2 CH 3 ,

- C(O)CH 3 ,

- C(O)NH 2 ,

- OCH 2 CH 2 OH,

- OCH 2 CH 2 NH 2 ,

- ONHC(NH)NH 2 ,

- OC(O)NH 2 ,

-Ooxetanyl,

- CH 2 CH 2 OH,

- CH 2 CH 2 CH 2 OH, -CH 2 CH 2 CH 3 ,

- CH 2 CH 2 OCH 3 ,

- CH 2 CH(OH)CH 3 , -CH 2 CH(OH)CH 2 OH, -CH 2 C(O)OCH 3 ,

- CH 2 C(O)NH 2 ,

- C(O)CH(CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 NHCH 2 CH 3 , -CH 2 CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 NHCH 2 C(CH 3 ) 3 , -CH 2 CH 2 N(CH 3 )CH 2 OCH 3 , -C(CH 3 ) 2 CH 2 OH, -CH 2 C(CH 3 ) 2 OH, -CH 2 C(CH 3 ) 2 OCH 3 , -C(O)CH 2 OH, -CH 2 isothiazolyl,

- CH 2 thiazolyl,

- CH 2 pyrazolyl,

- CH 2 imidazolyl,

- CH 2 pyridinyl,

- CH 2 oxazolyl,

- CH 2 pyrrolyl,

- CH 2 isoxazoly,

- CH 2 furanyl,

- CH 2 CH 2morpholinyl , -CH 2 CH 2 pyrrolidinyl, -CH 2 CH 2 pyrrolidinylCH 3 , -CH 2 CH 2 CH 2 pyrrolidinyl, -C(O)phenyl,

-C(O)C(tetrahydropyranyl)NH 2 , -NH 2 ,

- NHCH 3 ,

- N(CH 3 ) 2 ,

- NHC(O)CH 3 ,

- NHCH 2 CHF 2 ,

- NHCH 2 C(CH 3)3 ,

- NHCH 2 CH(CH 3)2 , -NHCH 2 CH 2 OCH 3 , -NHCH 2 CH 2 OH, -NHCH 2 CH 2 NH 2 , -NHCH 2 C(O)OH, -NHC(O)CH 2 NH 2 , -NHC(O)CH 2 CH 2 CH 2 NH 2 , -NHCH 2 C(O)NH 2 , -NHCH 2 C(OH)(CH 3 ) 2 , -NHC(O)CH(CH 3 )NH 2 , -NHC(O)OCH(CH 3 )NH 2 , -NHC(O)CH(CH 3 ) 2 , -NHC(O)C(CH 3 ) 2 NH 2 , -NHC(O)CH 2 OH, -NHC(O)CH(CH 2 OH)NH 2 , -NHC(O)(oxetanyl)NH 2 , -NHC(O)OC(CH 3 ) 3 , -NHC(CH 3 ) 2 C(O)OCH 3 , -NHcyclopropyl,

-NHoxetanyl,

- CH 2 NH 2 ,

- CH 2 CH 2 NH 2 , -CH 2 CH 2 CH 2 NH 2 , -CH 2 NHCH 2 C(CH 3 ) 3 , -CH 2 NHC(O)C(CH 3 ) 3 , -CH 2 NHC(O)CH 2 NH 2 , -CH 2 NHC(O)CH 2 OH, -CH 2 N(CH 3 ) 2 , -CH 2 NHCH 3 ,

- CH 2 N(CH 2 CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 ,

- S(O) 2 CH 2 CH 3 ,

- S(O) 2 CH 2 CH 2 CH 3 , -S(O) 2 phenyl,

- S(O) 2 CH 3 ,

benzoyl,

benzylamino,

3-pyrrolidinylpropyl,

2-cyclopropylmethyl, cyclobutylamino, cyclobutyl-N(CH 3 )-, piperidinyl,

imidazolyl,

morpholinyl,

morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinyl, pyrrolidinyl,

pyrrolidinylmethyl, methoxypyridinylmethylamino, methylpyrrolidinyl, difluoropyrrolidinyl, dimethylpyrrolidinyl, methylcyclopropylmethylamino, hydroxymethylpyrrolidinyl, fluoropyrrolidinyl, fluorophenylmethylamino,

piperazinylmethyl,

oxazolidinyl,

methyloxetanmethylamino,

methylcyclobutylmethylamino,

oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (Qb2) R 71c” is phenyl.

Suitably in the compounds of Formula (Qb2), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (Qb2), the compounds are in the form of a –C(O)CH(NH 2 )CH(CH 3 ) 2 prodrug. Non primary amide: This invention relates to compounds of Formula (Icr) and to the use of compounds of Formula (Icr) in the methods of the invention:

wherein:

X 1cr and X 2cr are independently selected from: hydrogen,

cyano,

fluoro,

chloro,

bromo,

iodo, C 1-6 alkyl,

R e ,

- OC 1-6 alkyl,

- OR e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycle,

h eterocycle substituted from 1 to 4 times by R d , -SH, and

- SR a ; Y cr is selected from: S, NH, NR z , O, S(O) and S(O)2; R 1cr is selected from: amino,

- NHR a ,

- NR b R c ,

cyano,

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

- OC 1-6 alkyl,

- OR e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycle,

h eterocycle substituted from 1 to 4 times by R d , aryl,

a ryl substituted from 1 to 4 times by R d , heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d , -SH, and

- SR a ; R 2cr is selected from: hydrogen,

C 1-6 alkyl, and

C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: halogen, -OH, -COOH; R 3cr is selected from: aryl,

a ryl substituted from 1 to 4 times by R d , heteroaryl, and

h eteroaryl substituted from 1 to 4 times by R d ; R 4cr is selected from: hydrogen,

C 1-6 alkyl, and

C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: halogen, -OH, -COOH; R 5cr is selected from: amino,

- NHR a ,

- NR b R c ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

- C 1-6 alkyl,

- OC 1-6 alkyl,

- OR e ,

-Oaryl,

- Oaryl substituted from 1 to 4 times by R d , -Oheteroaryl,

- Oheteroaryl substituted from 1 to 4 times by R d , -SH, and

- SR a ; where: each R a is independently selected from

C 1-6 alkyl,

R e ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d ,

heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d ; R b and R c are independently selected from:

C 1-6 alkyl,

R e ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d ;

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d ,

heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d , or

R b and R c are taken together with the nitrogen to which they are

attached, and optionally from 1 to 3 additional heteroatoms independently selected from O, N, and S, to form

a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C1-6alkyl,

R e ,

- OR e , aryl,

a ryl substituted from 1 to 4 times by R d , heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d , cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d , C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 ,

- N(H)C 1-5 alkyl,

- N(H)R e , -N(C 1-5 alkyl) 2 ,

- NR e R e ,

- N(R e )C1-5alkyl,

-ONHC(NH)NH 2 ,

-Oheterocycloalkyl,

-NHcycloalkyl,

- N(C 1-5 alkyl)cycloalkyl,

-NHheterocycloalkyl,

- N(C 1-5 alkyl)heterocycloalkyl, -S(O) 2 C 1-4 alkyl,

-SO 2 NH 2

- S(O) 2 phenyl,

benzoyl, 2-methylcyclopropyl,

imidazolyl,

(methoxypyridinylmethyl)amino,

(methylcyclopropylmethyl)amino,

(fluorophenylmethyl)amino,

(methyloxetanylmethyl)amino, and

(methylcyclobutylmethyl)amino; each R d is independently selected from: fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, fluoro, oxo, C1-6alkyl, and C1-6alkyl substituted

with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, aryl,

a ryl substituted from 1 to 4 times by R x , where R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , -NHC 1-4 alkyl, -N(C 1-4 alkyl) 2 and–-CN,

-Oaryl,

- Oaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- OR e ,

-C(O)H,

- C(O)R zz ,

-C(O)aryl,

- C(O)aryl substituted from 1 to 4 times by R zz ,

-C(O)heteroaryl,

- C(O)heteroaryl substituted from 1 to 4 times by R zz ,

-OC(O)H,

- CO(O)R zz ,

-OC(O)aryl,

- CO(O)aryl substituted from 1 to 4 times by R zz ,

-OC(O)heteroaryl,

- OC(O)heteroaryl substituted from 1 to 4 times by R zz , mercapto,

- SR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

-S(O)H,

- S(O)R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- S(O) 2 H,

- S(O)2R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- OS(O)2R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–-CN,

- S(O) 2 NH 2 ,

- S(O)2NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- S(O)2NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

- P(O)(CH 3 ) 2 ,

- NHS(O) 2 H,

- NHS(O)2R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–-CN,

-NHC(O)H,

- NHC(O)R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, -C(O)NH 2 ,

- C(O)NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- C(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–-CN,

-C(O)OH,

- C(O)OR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

oxo,

hydroxy,

amino,

- NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: f luoro, oxo, -OH, -COOH, -NH 2 , and -CN, C 1-6 alkoxy, and C 1-6 alkoxy substituted with from 1 to 6 substituents Independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–CN -NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, -S(O) 2 C 1-6 alkyl, -S(O) 2 C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , a nd -CN, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and -CN,

boronic acid,

nitro,

cyano,

- NHC(O)NH 2 ,

- NHC(O)NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, - NHC(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

e ach R e is independently selected from:

C1-6alkyl substituted with from 1 to 9 substitutents independently selected from:

fluoro,

chloro,

bromo,

iodo,

- OC 1-6 alkyl,

-OC1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- OC(O)C 1-6 alkyl,

- OC(O)C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and -CN,

-ONHC(NH)NH 2 ,

- OP(O)(OH) 2 ,

mercapto,

- SR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

-S(O)H,

- S(O)R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O) 2 H,

- S(O)2R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

oxo,

hydroxy,

amino,

- NHR xx ,

w here R xx is selected from aryl, heteroaryl, c ycloalkyl, cycloalkyl substituted with C 1-4 alkoxy, C 1-4 alkoxy substituted with from 1 to 6 substituents independently selected from: fluoro, triazolyl, cyclopropyl,oxo, -OR xy , -COOH,–CN, and -NR xy R xz , where R xy and R xz are Independently selected from: h ydrogen, aryl, C 1-5 alkyl heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OR xy , -COOH,–CN, and -NR xy R xz , where R xy and R xz are Independently selected from: hydrogen, aryl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, t riazolyl, cyclopropyl,oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH,

- NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

guanidino,

-C(O)OH,

- C(O)OR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- C(O)NH 2 ,

- C(O)NHR x ,

w here R x is selected from aryl, heteroaryl, -OH, C 1-4 alkoxy, cycloalkyl, cycloalkyl substituted with HO-(C1-4alkyl)-, heterocyloalkyl, heterocyloalkyl s ubstituted with HO-(C 1-4 alkyl)-, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, heteroaryl, -NH 2 , and–-CN,

- C(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, cycloalkyl substituted w ith HO-(C 1-4 alkyl)-, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–CN,

o r R x1 and R x2 taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms independently selected from O, N, and S, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from fluoro, oxo, -OH, HO- ( C 1-4 alkyl)-, -COOH, -NH 2 , and–CN,

aryl,

a ryl substituted from 1 to 4 times by R x ,

w here R x is selected from fluoro, chloro, bromo, iodo, aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , -N(CH 3 ) 2 , -NHC(O)C 1-4 alkyl, and -CN,

-Oaryl,

- Oaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-4 alkoxy C 1-6 alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and -CN,

-Oheteroaryl,

- Oheteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from oxo, -OH,

- N(C 1-4 alkyl) 2 , aryl, heteroaryl,

c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , -N(CH 3 ) 2 , and -CN,

- S(O) 2 NH 2 ,

- S(O)2NHR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O)2NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

-NHS(O)2H,

- NHS(O)2R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- OC(O)NH 2,

- NHC(O)R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and -CN

- NHC(O)NHR xp ,

w here R xp is selected from heteroaryl, c ycloalkyl, heterocyloalkyl, and C 1-6 alkyl substituted with from 1 to 4 substituents independently selected from: -COOH, -NH 2 , and –-CN,

- NHC(O)NR x3 R x4 , where R x3 and R x4 are each independently selected from heteroaryl, cycloalkyl, heterocyloalkyl, a nd C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from:

- COOH, -NH 2 , and–-CN,

- NHC(O)C(O)NH 2 ,

- NO 2 , and

-CN; and R z is selected from

C 1-6 alkyl,

R e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d ; and R zz is selected from

C 1-6 alkyl, and

R e ; provided that:

X 1cr and X 2cr are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof. Suitably in the compounds of Formula (Icr) neither X 1cr nor X 2cr are hydrogen. Suitably in the compounds of Formula (Icr), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (Icr), the compounds are in the form of a –C(O)CH(NH 2 )CH(CH 3 ) 2 prodrug.

Included in the compounds of the invention and used in the methods of the invention are compounds of Formula (IIcr): wherein: X 21cr and X 22cr are independently selected from: hydrogen,

cyano,

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

- OC 1-6 alkyl,

- OR e ,

cycloalkyl,

heterocycle, and

-SH; Y 1cr is selected from: S, NH, and NR z

; R 21cr is selected from: amino,

cyano,

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

- OC 1-6 alkyl,

- OR e ,

- NHR a ,

- NR b R c ,

aryl,

a ryl substituted from 1 to 4 times by R d , heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d , cycloalkyl,

c ycloalkyl substituted with from 1 to 4 times by R d , heterocycle,

h eterocycle substituted with from 1 to 4 times by R d , -SH, and

- SR a ; R 22cr is selected from: hydrogen,

C 1-6 alkyl, and

C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, chloro, and bromo; R 23cr is selected from: aryl,

a ryl substituted from 1 to 4 times by R d ,

heteroaryl, and

h eteroaryl substituted from 1 to 4 times by R d ; R 24cr is selected from: hydrogen,

C 1-6 alkyl, and

C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, chloro, and bromo; R 25cr is selected from: amino,

- NHR a ,

- NR b R c ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

- OC 1-6 alkyl, -OR e ,

-Oaryl,

-Oheteroaryl,

-SH, and

- SR a ; where: e ach R a is independently selected from

C1-6alkyl,

R e ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d ,

heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d ; R b and R c are independently selected from:

C 1-6 alkyl,

R e ,

aryl,

a ryl substituted from 1 to 4 times by R d ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d ;

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d ,

heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d , or

R b and R c are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo, iodo,

C 1-6 alkyl,

R e ,

- OR e ,

aryl,

a ryl substituted from 1 to 4 times by R d , heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d , cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d , C 1-4 alkoxy, C 1-4 alkoxy substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–-CN,

–-CN,

oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 ,

- N(H)C 1-4 alkyl,

- N(H)R e , -N(C 1-4 alkyl) 2 ,

-ONHC(NH)NH2,

-Oheterocycloalkyl,

-NHcycloalkyl,

-NHheterocycloalkyl,

- S(O) 2 CH 2 CH 3 , -S(O) 2 CH 2 CH 2 CH 3 , -S(O) 2 phenyl, -S(O) 2 CH 3 ,

benzoyl,

benzylamino,

3-pyrrolidinylpropyl, 2-cyclopropylmethyl, cyclobutylamino, cyclobutyl-N(CH3)-, piperidinyl,

imidazolyl,

morpholinyl,

morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinyl, pyrrolidinyl,

pyrrolidinylmethyl, methoxypyridinylmethylamino, methylpyrrolidinyl, difluoropyrrolidinyl, dimethylpyrrolidinyl, methylcyclopropylmethylamino, hydroxymethylpyrrolidinyl, fluoropyrrolidinyl, fluorophenylmethylamino, piperazinylmethyl, oxazolidinyl,

methyloxetanmethylamino, methylcyclobutylmethylamino, oxoimidazolidinyl, and 2-hydroxyethylpiperidinyl; each R d is independently selected from: fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, fluoro, oxo, C 1-6 alkyl, and C 1-6 alkyl substituted

with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, aryl,

a ryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 4 substituents independently selected

from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, -Oaryl, -Oaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

-C(O)H,

- C(O)R zz ,

-C(O)aryl,

- C(O)aryl substituted from 1 to 4 times by R zz ,

-C(O)heteroaryl,

- C(O)heteroaryl substituted from 1 to 4 times by R zz , -OC(O)H,

- CO(O)R zz ,

-OC(O)aryl,

- CO(O)aryl substituted from 1 to 4 times by R zz ,

-OC(O)heteroaryl,

- OC(O)heteroaryl substituted from 1 to 4 times by R zz , mercapto,

- SR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

-S(O)H,

- S(O)R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- S(O) 2 H,

- S(O)2R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- OS(O)2R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- S(O) 2 NH 2 ,

- S(O)2NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- S(O)2NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

- NHS(O) 2 H,

- NHS(O)2R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

-NHC(O)H,

- NHC(O)R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- C(O)NH 2 ,

- C(O)NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- C(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

-C(O)OH,

- C(O)OR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

oxo,

hydroxy,

amino,

- NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, -S(O)2C1-6alkyl, - S(O) 2 C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and

-CN, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH,

- NH 2 , and–-CN,

boronic acid,

nitro,

cyano,

- NHC(O)NH 2 ,

- NHC(O)NHR x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- NHC(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from a ryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, - NH 2 , and–-CN,

e ach R e is independently selected from:

C 1-6 alkyl substituted with from 1 to 9 substitutents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

- OC 1-6 alkyl,

- OC 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

mercapto,

- SR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

-S(O)H,

- S(O)R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O) 2 H,

- S(O)2R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

oxo,

hydroxy, amino,

- NHR xx ,

w here R xx is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl,

a nd C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, o xo, -ORxy, -COOH,–-CN, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and –NR xy R xz , where R xy and R xz are independently s elected from: hydrogen, aryl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, - OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH,

- NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

guanidino,

-C(O)OH,

- C(O)OR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- C(O)NH 2 ,

- C(O)NHR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN, -C(O)NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

aryl,

a ryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

-Oaryl,

- Oaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

-Oheteroaryl,

- Oheteroaryl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O) 2 NH 2 ,

- S(O)2NHR x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O)2NR x1 R x2 ,

w here R x1 and R x2 are each independently selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN,

- NHS(O) 2 H,

- NHS(O)2R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- NHC(O)NHR xp ,

w here R xp is selected from heteroaryl, c ycloalkyl, heterocyloalkyl, and C 1-6 alkyl substituted with from 1 to 4 substituents independently selected from: -COOH, -NH 2 , and –-CN,

- NHC(O)NR x3 R x4 ,

w here R x3 and R x4 are each independently selected from heteroaryl, cycloalkyl, heterocyloalkyl,

a nd C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from:

- COOH, -NH 2 , and–-CN,

nitro, and

cyano; R z is selected from

C 1-6 alkyl,

R e ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d ; R zz is selected from

C1-6alkyl, and

R e ; provided that:

X 21cr and X 22cr are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof. Suitably in the compounds of Formula (IIcr) neither X 21cr nor X 22cr are hydrogen. Suitably in the compounds of Formula (IIcr), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (IIcr), the compounds are in the form of a –C(O)CH(NH 2 )CH(CH 3 ) 2 prodrug.

Included in the compounds of the invention and used in the methods of the invention are compounds of Formula (IIIcr): cr)

wherein:

X 31cr and X 32cr are independently selected from: hydrogen,

cyano,

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

- OC 1-6 alkyl,

cycloalkyl, and

-SH; Y 2cr is selected from: S, NH, and NR z

; R 31cr is selected from: C 1-6 alkyl,

R e1 ,

- OC 1-6 alkyl,

- OR e1 ,

- NHR a1 ,

- NR b1 R c1 ,

aryl,

a ryl substituted from 1 to 4 times by R d1 , heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d1 , cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d1 , heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R d1 , -SH, and

- SR a1 ; R 32cr is selected from: hydrogen,

C 1-3 alkyl, and

C 1-3 alkyl substituted from 1 to 4 times by fluoro; R 33cr is selected from: aryl,

a ryl substituted from 1 to 4 times by R d1 , heteroaryl, and

h eteroaryl substituted from 1 to 4 times by R d1 ; R 34cr is selected from: hydrogen,

C 1-3 alkyl, and

C 1-3 alkyl substituted from 1 to 4 times by fluoro; R 35cr is selected from: amino,

- NHR a1 ,

- NR b1 R c1 ,

aryl,

a ryl substituted from 1 to 4 times by R d1 , - OC 1-6 alkyl,

- OR e1 ,

-SH, and

- SR a1 ; where: e ach R a1 is independently selected from

C 1-6 alkyl,

R e1 ,

aryl,

heteroaryl, cycloalkyl,

heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d1 ; R b1 and R c1 are independently selected from:

C 1-6 alkyl,

R e1 ,

- OR e1 ,

aryl,

a ryl substituted from 1 to 4 times by R d1 ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R d1 ;

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d1 ,

heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d1 , or R b1 and R c1 are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e1 ,

aryl,

a ryl substituted from 1 to 4 times by R d1 , cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d1 , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d1 , C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, –-CN,

oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 ,

- N(H)C 1-4 alkyl,

- N(H)R e1 , -N(C 1-4 alkyl) 2 ,

-ONHC(NH)NH 2 ,

-Oheterocycloalkyl,

-NHcycloalkyl,

-NHheterocycloalkyl,

- S(O) 2 CH 2 CH 3 ,

- S(O) 2 CH 2 CH 2 CH 3 ,

- S(O) 2 phenyl,

- S(O) 2 CH 3 ,

benzoyl,

benzylamino,

3-pyrrolidinylpropyl,

2-cyclopropyl methyl, cyclobutylamino,

c yclobutyl-N(CH 3 )-, piperidinyl,

imidazolyl,

morpholinyl,

morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinyl, pyrrolidinyl,

pyrrolidinylmethyl,

methoxypyridinylmethylamino,

methylpyrrolidinyl,

difluoropyrrolidinyl,

dimethylpyrrolidinyl,

methylcyclopropylmethylamino,

hydroxymethylpyrrolidinyl,

fluoropyrrolidinyl,

fluorophenylmethylamino,

piperazinylmethyl,

oxazolidinyl,

methyloxetanmethylamino,

methylcyclobutylmethylamino,

oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl; each R d1 is independently selected from: fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

R e1 ,

heteroaryl,

h eteroaryl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R x , where R x is selected from: fluoro, oxo, C 1-6 alkyl, and C 1- 6 alkyl

substituted with from 1 to 6 substituents independently selected

from: fluoro, oxo, -OH, -COOH, -NH 2 , and–-CN, aryl,

a ryl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 4 substituents independently selected from: fluoro and -NH 2 ,

-Oaryl,

-C(O)H,

- C(O)R zz ,

-C(O)aryl,

-C(O)heteroaryl,

-OC(O)H,

- CO(O)R zz ,

-OC(O)aryl,

-OC(O)heteroaryl,

mercapto,

- SR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted from 1 to 6 times by fluoro,

-S(O)H,

- S(O)R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- S(O) 2 H,

- S(O)2R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- OS(O)2R xa , where R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- S(O) 2 NH 2 ,

- S(O)2NHR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- NHS(O) 2 H,

- NHS(O)2R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted from 1 to 6 times by fluoro,

-NHC(O)H,

- NHC(O)R xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- C(O)NH 2 ,

- C(O)NHR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

-C(O)OH,

- C(O)OR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

oxo,

hydroxy,

amino,

- NR x1a R x2a ,

w here R x1a and R x2a are each independently selected from - S(O) 2 C 1-6 alkyl, and C 1-6 alkyl,

- NHR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

nitro,

cyano,

boronic acid,

- NHC(O)NH 2 , and

- NHC(O)NHR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, h eterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro; each R e1 is independently selected from:

C 1-6 alkyl substituted with from 1 to 9 substitutents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

- OC 1-6 alkyl,

- OC 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

mercapto,

- SR xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

-S(O)H,

- S(O)R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- S(O) 2 H,

- S(O)2R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro, oxo, hydroxy,

amino,

- NHR xx ,

w here R xx is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl,

a nd C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, o xo, -ORxy, -COOH,–-CN, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and –NR xy R xz , where R xy and R xz are independently s elected from: hydrogen, aryl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, - OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH,

- NR x1x R x2x ,

w here R x1x and R x2x are each independently s elected from C 1-4 alkyl, and C 1-4 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, and–OH,

guanidino,

-C(O)OH,

- C(O)OR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, heterocyloalkyl, C1-6alkyl, and C1-6alkyl substituted from 1 to 6 times by fluoro,

- C(O)NHR xa ,

w here R xa is selected from aryl, heteroaryl, cycloalkyl, and heterocyloalkyl,

aryl,

a ryl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

-Oaryl, -Oaryl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro, heteroaryl,

h eteroaryl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

-Oheteroaryl,

- Oheteroaryl substituted from 1 to 4 times by R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro, cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R x ,

w here R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

heterocycloalkyl,

h eterocycloalkyl substituted from 1 to 4 times by R x , where R x is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

- S(O) 2 NH 2 ,

- S(O)2NHR xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro,

- NHS(O) 2 H,

- NHS(O)2R xa ,

w here R xa is selected from aryl, heteroaryl, c ycloalkyl, heterocyloalkyl, C 1-6 alkyl, and C 1-6 alkyl substituted from 1 to 6 times by fluoro, -NHC(O)NHR xa ,

w here R xa is selected from heteroaryl, cycloalkyl, and heterocyloalkyl,

nitro, and

cyano; R z is selected from

C 1-6 alkyl,

R e1 ,

cycloalkyl,

c ycloalkyl substituted from 1 to 4 times by R d1 , heterocycloalkyl, and

h eterocycloalkyl substituted from 1 to 4 times by R d1 ; R zz is selected from

C 1-6 alkyl, and

R e1 ; provided that:

X 31cr and X 32cr are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof. Suitably in the compounds of Formula (IIIcr), neither X 31cr nor X 32cr are hydrogen. Suitably in the compounds of Formula (IIIcr), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (IIIcr), the compounds are in the form of a –C(O)CH(NH2)CH(CH3)2 prodrug.

This invention relates to novel compounds of Formula (IVccr) and to the use of compounds of Formula (IVccr) in the methods of the invention:

wherein:

X 41ccr and X 42ccr are independently selected from: --CN, methyl, fluoro, chloro, bromo and

iodo;

Y 4ccr is selected from: S and NH; R 41ccr is selected from: C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo,

i odo, oxo, C 1-4 alkyloxy, -OH, -COOH, -NH 2 - N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 and–-CN,

C 1-4 alkyloxy, C 1-4 alkyloxy substituted from 1 to 4 times by fluoro,

- N(H)C 1-4 alkyl,

- N(C 1-4 alkyl) 2 ,

- SC 1-4 alkyl,

aryl,

aryl substituted with from 1 to 4 substituents

independently selected from:

fluoro,

chloro,

bromo,

iodo, C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN,

C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-NO 2 , and

-NH 2 ,

heteroaryl,

heteroaryl substituted with from 1 to 4 substituents

independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN,

C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-NO 2 , and

-NH 2 ,

cycloalkyl,

cycloalkyl substituted with from 1 to 4 substituents

independently selected from: fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN,

C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-NO 2 , and

-NH 2 ;

R 43ccr is selected from:

aryl,

aryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-4 alkoxy,

C1-4alkoxy substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, oxo, - OH, -NH 2 , -NHCH 3 , and–N(CH 3 ) 2 , C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -S(O) 2 C 1-4 alkyl, --CN, -OR49 and – NR 46 R 47 ,

where R 46 and R 47 are independently s elected from: hydrogen, -S(O) 2 CH 3 , pyrazole, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 48 R 49 , where R 48 and R 49 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, –-CN,

oxo,

-OH,

heterocycloalkyl,

heterocycloalkyl independently substituted once or twice with a substituent selected from: fluoro and oxo,

- N(CH 3 )S(O) 2 CFH 2 ,

- N(CH 3 )S(O) 2 CF 2 H,

- N(CH 3 )S(O) 2 CF 3 ,

- OS(O) 2 CH 3 ,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 ,

–NR 80a’ R 81a’ where R 80a’ and R 81a’ are independently s elected form: hydrogen, -S(O) 2 CH 3 , phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -NH 2 , -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH,

boronic acid,

-NO2, and

-NH 2 ,

heteroaryl, and

heteroaryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 49 and–NR 46 R 47 ,

where R 46 and R 47 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 48 R 49 , where R 48 and R 49 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, C 1-4 alkoxy,

–-CN,

oxo,

-OH,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 ,

-NO 2 , and

-NH 2 ; and

R 44ccr and R 45ccr are independently selected from:

hydrogen, C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: phenyl, morpholino, triazolyl, i midazolyl, pyrrolidinyl, -OC(O)NH 2 , -OCH 2 CH 2 NH 2 ,

- ONHC(NH 2 )NH 2 , -NHCH 2 C(CH 3 ) 3 , -NOCH 3 , -NHOH, -NHCH 2 CH 2 F, -N(CH 3 )CH 2 CH 2 OCH 3 , -N(CH 2 CH 3 ) 2 , -NCH(CH 2 OH) 2 , -N(CH 2 CH 2 OH) 2 , -NHCH 2 CH 2 OH,

- NHCH 2 CH 2 NH 2 , -N(CH 3 )C(CH 3 ) 2 CH 2 OH, -NHCH 2 CH 3 , -NHCH 2 CH 2 OCH 3 , -N(CH 3 )CH 2 CH 2 OH, -NHC(O)C(O)NH 2 , -N(CH 3 )CH 2 CH 2 CH 2 OH, -N(CH 3 )CH 2 CH(OH)CH 2 OH, -N(CH 3 )CH 2 CH 2 NH 2 , oxo, -NHCH 2 C(CH 3 ) 2 CH 2 OH, -OH, -NH 2 , -NHCH 3 , -NHCH 2 CH 2 CH 2 OH, -N(CH 3 ) 2 , -N(CH 3 )CH 2 CH 3 , -NHOC(CH 3 ) 2 NH 2 , -N(CH 3 )CH 2 cyclopropyl, -NHCH 2 cyclopropyl, -NHoxetanyl, -NCH 2 CH 2 triazole, piperazinyl, piperidinyl, pyrazolyl, azepinyl, azetidinyl, methoxy, and cyclopropylamino,

where said phenyl, morpholino, triazolyl, imidazolyl, azepinyl, azetidinyl, pyrrolidinyl piperazinyl, piperidinyl, oxetanyl, cyclopropyl, and pyrazolyl are optionally substituted with from 1 to 4 substituents independently selected from: methyl, fluoro, -NH 2 , -N(CH3)2, hydroxymethyl, oxo, -OH, and–CH2NH2, cycloalkyl,

cycloalkyl substituted with from one to five substituents

independently selected from:

fluoro,

chloro,

-OH,

C 1-6 alkyl, and

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro; heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN, aryl,

C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

–-CN,

oxo,

-OH,

-COOH,

-NO 2 ,

-NH 2 , and

SO 2 NH 2, or

R 44ccr and R 45ccr are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms independently selected from O, N, and S, to form

a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl-, -OH, -NH 2 , -N(H)C 1-5 alkyl, aminoheterocycloalkyl-, -N(C 1-5 alkyl) 2 , --CN, -N(C 1-4 alkyl)(CH 2 OCH 3 ), and -NHC 1-4 alkyl substituted by one or two substituents independently selected from oxo, NH 2 , and -OH,

aryl,

cycloalkyl,

heterocycloalkyl, heterocycloalkyl substituted with from 1 to 9 substituents i ndependently selected from: C 1-6 alkyl,

- C 1-6 alkylOH, fluoro, -C 1-6 alkylNH 2 ,

chloro, bromo, iodo, oxo, -OH, -NH 2 and–-CN, C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

-CN,

oxo,

-OH,

- OP(O)(OH) 2 ,

-COOH,

-NO 2 ,

-NH 2 ,

- N(H)C 1-5 alkyl,

- N(H)C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, bromo, i odo, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, aminoC 1-4 alkoxy, heterocycloalkyl,

m ethylheterocycloalkyl, -OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and -CN,

-Ooxetanyl,

-ONHC(NH)NH 2 ,

-NHcyclopropyl,

-NHoxetanyl,

- N(C 1-5 alkyl) 2,

- S(O) 2 CH 2 CH 3 , S(O) 2 CH 2 CH 2 CH 3 ,

- S(O) 2 CH 3, -SO 2 NH 2, - S(O) 2 phenyl,

benzoyl, benzylamino, -propylpyrrolidinyl,

-methylcyclopropyl, cyclobutylamino,

c yclobutyl-N(CH 3 )-, piperidinyl, imidazolyl, morpholinyl, morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinyl,

pyrrolidinyl, pyrrolidinylmethyl,

(methoxypyridinylmethyl)amino, methylpyrrolidinyl,

difluoropyrrolidinyl, dimethylpyrrolidinyl,

(methylcyclopropylmethyl)amino, hydroxymethylpyrrolidinyl, fluoropyrrolidinyl,

fluorophenylmethylamino, piperazinlymethyl,

oxazolidinyl, (methyloxetanmethyl)amino, (methylcyclobutylmethyl)amino, oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl; provided that: R 44ccr and R 45ccr are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (IVccr), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (IVccr), the compounds are in the form of a–C(O)CH(NH 2 )CH(CH 3 ) 2 prodrug.

Suitably in the compounds of Formula (IVccr) neither R 44ccr nor R 45ccr is hydrogen. Suitably in the compounds of Formula (IVccr) R 43ccr is aryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

bromo,

iodo,

heterocycloalkyl,

heterocycloalkyl independently substituted once or twice a substituent selected from: fluoro and oxo,

- OS(O) 2 CH 3 ,

- N(CH 3 )S(O) 2 CH 3 ,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, i odo, oxo, -S(O) 2 C 1-4 alkyl, --CN, -OR49 and – NR 46 R 47 ,

where R 46 and R 47 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC 1-5 alkyl,

- OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 48 R 49 , where R 48 and R 49 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH. This invention relates to novel compounds of Formula (Vccr) and to the use of compounds of Formula (Vccr) in the methods of the invention:

wherein:

Y 5ccr is selected from: S and NH; R 50ccr is selected from: C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro, - N(H)C 1-4 alkyl,

- N(C 1-4 alkyl) 2 ,

- SC 1-4 alkyl, C 1-4 alkyloxy, aryl,

aryl substituted with from one to five substituents

independently selected from:

fluoro,

chloro,

-OH,

C 1-6 alkyl, and

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro, heteroaryl,

heteroaryl substituted with from one to five substituents

independently selected from:

fluoro,

chloro,

-OH,

C 1-6 alkyl, and

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro, cycloalkyl,

cycloalkyl substituted with from one to five substituents

independently selected from:

fluoro,

chloro,

-OH,

C 1-6 alkyl, and C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro; R 52ccr is selected from:

aryl,

aryl substituted with from 1 to 4 substituents independently selected from: fluoro,

chloro,

C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, oxo, - OH, -NH 2 , -NHCH 3 , and–N(CH3)2,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, i odo, oxo, -S(O) 2 CH 3 , --CN, -OR59 and–NR56R57, where R 56 and R 57 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 58 R 59 , where R 58 and R 59 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, oxo,

--CN,

tetrahydroisothiazolyl,

tetrahydroisothiazolyl substituted twice by oxo, tetrahydro-1,2-thiazinyl,

tetrahydro-1,2-thiazinyl substituted twice by oxo, -N(CH 3 )S(O) 2 CH 3 ,

- N(CH 3 )S(O) 2 CFH 2 ,

- N(CH 3 )S(O) 2 CF 2 H,

- N(CH 3 )S(O) 2 CF 3 ,

- OS(O) 2 CH 3 ,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 ,

–NR 80a’ R 81a’ where R 80a’ and R 81a’ are independently s elected form: hydrogen, -S(O) 2 CH 3 , phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -NH 2 , -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, and

-OH;

heteroaryl, and

heteroaryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, iodo, oxo, --CN, -OR 59 and–NR 56 R 57 ,

where R 56 and R 57 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 58 R 59 , where R 58 and R 59 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, oxo,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 ,

-OH; and

R 53ccr and R 54ccr are independently selected from:

hydrogen,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: phenyl, morpholino, triazolyl, i midazolyl, -CH 2 CH 2 pyrrolidinyl, -OC(O)NH 2 , -OCH 2 CH 2 NH 2 , -ONHC(NH 2 )NH 2 , -NHCH 2 C(CH 3 ) 3 , -NOCH 3 , -NHOH, -NHCH 2 CH 2 F, -N(CH 3 )CH 2 CH 2 OCH 3 , -N(CH 2 CH 3 ) 2 , -NCH(CH 2 OH) 2 , -N(CH 2 CH 2 OH) 2 , -NHCH 2 CH 2 OH, -NHCH 2 CH 2 NH 2 , -N(CH 3 )CH 2 (CH 3 ) 2 CH 2 OH, -NHCH 2 CH 3 , -NHCH 2 CH 2 OCH 3 , -N(CH 3 )CH 2 CH 2 OH, -NHC(O)C(O)NH 2 , -N(CH 3 )CH 2 CH 2 CH 2 OH, -N(CH 3 )CH 2 CH(OH)CH 2 OH, -N(CH 3 )CH 2 CH 2 NH 2 , oxo, -NHCH 2 C(CH 3 ) 2 CH 2 OH, -OH, -NH 2 , -NHCH 3 , -NHCH 2 CH 2 CH 2 OH, -N(CH 3 ) 2 , -N(CH 3 )CH 2 CH 3 , -NHOC(CH 3 ) 2 NH 2 , -N(CH 3 )CH 2 cyclopropyl, -NHCH 2 cyclopropyl, -NHoxetanyl, -NCH 2 CH 2 triazole, piperazinyl, piperidinyl, pyrazolyl, azepinyl, azetidinyl, methoxy, and cyclopropylamino,

where said phenyl, morpholino, triazolyl, imidazolyl, azepinyl, azetidinyl, pyrrolidinyl piperazinyl, piperidinyl, oxetanyl, cyclopropyl, and pyrazolyl are optionally substituted with from 1 to 4 substituents independently selected from: methyl, fluoro, -NH2, -N(CH3)2, hydroxymethyl, oxo, -OH, and–CH2NH2, cycloalkyl,

cycloalkyl substituted with from one to five substituents

independently selected from:

fluoro,

chloro,

-OH,

C 1-6 alkyl, and

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro; heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro and chloro, C 1-4 alkoxy, and

-OH, or

R 53ccr and R 54ccr are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, C1-4alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, -OH, -NH2, -N(H)C1-5alkyl, a minoheterocycloalkyl, -N(C 1-5 alkyl) 2 , --CN, -N(C 1-4 alkyl)(CH 2 OCH 3 ), and -NHC 1-4 alkyl substituted by one or two substituents independently selected from oxo, NH 2 , and -OH,

heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents i ndependently selected from: C 1-6 alkyl, -C 1-6 alkylOH, fluoro, -C 1-6 alkylNH 2 , chloro, oxo and -OH,

C 1-4 alkoxy, C 1-4 alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, -COOH, -NH2, and–-CN,

–-CN,

oxo,

-OH,

- OP(O)(OH) 2 ,

-COOH,

-CONH 2 , -NH 2 ,

- N(H)C 1-4 alkyl,

- N(H)C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl,

a minoC 1-4 alkoxy, heterocycloalkyl,

m ethylheterocycloalkyl, -OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and–-CN,

-Ooxetanyl,

-ONHC(NH)NH 2 ,

-NHcyclopropyl,

-NHoxetanyl,

- N(C 1-4 alkyl) 2,

- S(O) 2 CH 2 CH 3 ,

S (O) 2 CH 2 CH 2 CH 3 ,

- S(O) 2 CH 3,

- S(O) 2 phenyl,

benzoyl,

benzylamino,

-propylpyrrolidinyl,

-methylcyclopropyl,

cyclobutylamino,

c yclobutyl-N(CH 3 )-,

piperidinyl,

imidazolyl,

morpholinyl,

morpholinylmethyl,

methylpiperazinylmethyl,

methylpiperazinlyl pyrrolidinyl,

pyrrolidinylmethyl,

(methoxypyridinylmethyl)amino, methylpyrrolidinyl,

difluoropyrrolidinyl,

dimethylpyrrolidinyl,

(methylcyclopropylmethyl)amino, hydroxymethylpyrrolidinyl,

fluoropyrrolidinyl,

fluorophenylmethylamino,

piperazinylmethyl,

oxazolidinyl,

(methyloxetanylmethyl)amino,

(methylcyclobutylmethyl)amino, oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl;

provided that:

R 53ccr and R 54ccr are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (Vccr), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (Vccr), the compounds are in the form of a –C(O)CH(NH 2 )CH(CH 3 ) 2 prodrug.

Suitably in the compounds of Formula (Vccr) neither R 53ccr nor R 54ccr is hydrogen. Suitably in the compounds of Formula (Vccr) R 52ccr is aryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

tetrahydrothiazolyl, tetrahydrothiazolyl substituted twice by oxo,

tetrahydrothiazinyl,

tetrahydrothiazinyl substituted twice by oxo,

- N(CH 3 )S(O) 2 CH 3 ,

- OS(O) 2 CH 3 ,

C 1-6 alkyl,

C1-6alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, bromo, i odo, oxo, -S(O) 2 CH 3 , --CN, -OR59 and–NR56R57, where R 56 and R 57 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 58 R 59 , where R 58 and R 59 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH.

This invention relates to novel compounds of Formula (VIccr) and to the use of compounds of Formula (VIccr) in the methods of the invention:

wherein: Y 6ccr is selected from: S and NH; R 60ccr is selected from: C 1-3 alkyl,

C 1-3 alkyl substituted with from 1 to 6 substituents independently selected from: fluoro and chloro, - N(H)C 1-3 alkyl,

- N(C 1-3 alkyl) 2 ,

- SC 1-4 alkyl,

C1-3alkyloxy,

aryl,

aryl substituted with from one to 3 substituents

independently selected from:

fluoro,

chloro,

-OH, and

C 1-3 alkyl,

heteroaryl,

heteroaryl substituted with from one to 3 substituents independently selected from:

fluoro,

chloro,

-OH, and

C 1-3 alkyl, cycloalkyl,

cycloalkyl substituted with from one to 3 substituents

independently selected from:

fluoro,

chloro,

-OH, and

C 1-3 alkyl;

R 62ccr is selected from:

phenyl,

phenyl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

--CN,

oxo,

C 1-4 alkoxy, C 1-4 alkoxy substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, oxo, -OH, -NH2, -NHCH3, and–N(CH3)2, C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 5 substituents

independently selected from: fluoro, chloro, bromo, i odo, oxo, -S(O) 2 CH 3 , --CN, -OR69 and–NR66R67, where R 66 and R 67 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 68 R 69 , where R 68 and R 69 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, tetrahydroisothiazolyl,

tetrahydroisothiazolyl substituted twice by oxo, tetrahydro-1,2-thiazinyl,

tetrahydro-1,2-thiazinyl substituted twice by oxo, - N(CH 3 )S(O) 2 CH 3 ,

- N(CH 3 )S(O) 2 CFH 2 ,

- N(CH 3 )S(O) 2 CF 2 H,

- N(CH 3 )S(O) 2 CF 3 ,

- OS(O) 2 CH 3 ,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 , and

–NR 80a’ R 81a’ where R 80a’ and R 81a’ are independently s elected form: hydrogen, -S(O) 2 CH 3 , phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -NH 2 , -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH,

hetroaryl, and

hetroaryl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro, C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 5 substituents

independently selected from: fluoro, chloro, bromo, i odo, oxo, -S(O) 2 CH 3 , --CN, -OR69 and–NR66R67, where R 66 and R 67 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 68 R 69 , where R 68 and R 69 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, -S(O) 2 NH 2 , and

-S(O) 2 NHCH 3 ; and

R 63ccr and R 64ccr are independently selected from:

hydrogen,

C 1-4 alkyl,

C 1-4 alkyl substituted with from 1 to 4 substituents

independently selected from: phenyl, morpholino, triazolyl, i midazolyl, -CH 2 CH 2 pyrrolidinyl, -OC(O)NH 2 , -OCH 2 CH 2 NH 2 , -ONHC(NH 2 )NH 2 , -NHCH 2 C(CH 3 ) 3 , -NOCH 3 , -NHOH, -NHCH 2 CH 2 F, -N(CH 3 )CH 2 CH 2 OCH 3 , -N(CH 2 CH 3 ) 2 , -NCH(CH 2 OH) 2 , -N(CH 2 CH 2 OH) 2 , -NHCH 2 CH 2 OH,

- NHCH 2 CH 2 NH 2 , -N(CH 3 )CH 2 (CH 3 ) 2 CH 2 OH, -NHCH 2 CH 3 , -NHCH 2 CH 2 OCH 3 , -N(CH 3 )CH 2 CH 2 OH, -NHC(O)C(O)NH 2 , -N(CH 3 )CH 2 CH 2 CH 2 OH, -N(CH 3 )CH 2 CH(OH)CH 2 OH,

- N(CH 3 )CH 2 CH 2 NH 2 , oxo, -NHCH 2 C(CH 3 ) 2 CH 2 OH, -OH, -NH 2 , -NHCH 3 , -NHCH 2 CH 2 CH 2 OH, -N(CH 3 ) 2 , -N(CH 3 )CH 2 CH 3 , -NHOC(CH 3 ) 2 NH 2 , -N(CH 3 )CH 2 cyclopropyl, -NHCH 2 cyclopropyl, -NHoxetanyl, -NCH 2 CH 2 triazole, piperazinyl, piperidinyl, pyrazolyl, azepinyl, azetidinyl, methoxy, and cyclopropylamino,

where said phenyl, morpholino, triazolyl, imidazolyl, azepinyl, azetidinyl, pyrrolidinyl piperazinyl, piperidinyl, oxetanyl, cyclopropyl, and pyrazolyl are optionally substituted with from 1 to 4 substituents independently selected from: methyl, fluoro, -NH 2 , - N(CH 3 ) 2 , hydroxymethyl, oxo, -OH, and–CH 2 NH 2 , cycloalkyl,

cycloalkyl substituted with from 1 to 5 substituents independently

selected from:

fluoro,

chloro,

-OH, and

C 1-6 alkyl,

heterocycloalkyl, and

heterocycloalkyl substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

-OH, and

C 1-6 alkyl, or R 63ccr and R 64ccr are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms independently selected from O, N, and S, to form a heterocycloalkyl, to form a heterocycloalkyl, which is optionally substituted with from 1 to 5 substituents independently selected from:

fluoro,

chloro,

-OH,

- OP(O)(OH) 2,

--CN,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 9 substituents

independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl, heterocycloalkyl, methylheterocycloalkyl, -OH, -NH 2 , -N(H)C 1-5 alkyl, aminoheterocycloalkyl, -N(C 1-5 alkyl) 2 , --CN, -N(C1-4alkyl)(CH2OCH3), and -NHC1-4alkyl substituted by one or two substituents independently selected from oxo, NH 2 , and -OH,

heterocycloalkyl,

heterocycloalkyl substituted with from 1 to 9 substituents i ndependently selected from: C 1-6 alkyl,

- C 1-6 alkylOH, fluoro, chloro, oxo and -OH, C 1-4 alkoxy, C 1-4 alkoxy substituted with from 1 to 4 substituents

independently selected from: fluoro, oxo, -OH, - COOH, -NH 2 , and–-CN,

oxo, -NH 2 ,

- N(H)C 1-4 alkyl, -N(H)C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro, chloro, C 1-4 alkoxy, oxo, phenyl, cycloalkyl,

a minoC 1-4 alkoxy, heterocycloalkyl, methylheterocycloalkyl, -OH, -NH 2 , -N(H)C 1-4 alkyl, -N(C 1-4 alkyl) 2 , and–-CN,

- ONHC(NH)NH 2 ,

-Ooxetanyl,

-ONHC(NH)NH 2 ,

-NHcyclopropyl,

-NHoxetanyl,

- N(C 1-4 alkyl) 2,

- S(O) 2 CH 2 CH 3 ,

S (O) 2 CH 2 CH 2 CH 3 ,

- S(O) 2 CH 3,

- S(O) 2 phenyl,

benzoyl,

benzylamino,

-propylpyrrolidinyl,

-methylcyclopropyl,

cyclobutylamino,

c yclobutyl-N(CH 3 )-,

piperidinyl,

imidazolyl,

morpholinyl,

morpholinylmethyl, methylpiperazinylmethyl,

methylpiperazinyl,

pyrrolidinyl,

pyrrolidinylmethyl,

(methoxypyridinylmethyl)amino, methylpyrrolidinyl,

difluoropyrrolidinyl,

dimethylpyrrolidinyl,

(methylcyclopropylmethyl)amino, hydroxymethylpyrrolidinyl,

fluoropyrrolidinyl,

(fluorophenylmethyl)amino,

piperazinylmethyl,

oxazolidinyl,

(methyloxetanylmethyl)amino,

(methylcyclobutylmethyl)amino, oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl;

provided that:

R 63ccr and R 64ccr are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (VIccr), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (VIccr), the compounds are in the form of a–C(O)CH(NH 2 )CH(CH 3 ) 2 prodrug.

Suitably in the compounds of Formula (VIccr) neither R 63ccr nor R 64ccr is hydrogen. Suitably in the compounds of Formula (VIccr) R 62ccr is phenyl substituted with from 1 to 4 substituents independently selected from:

fluoro, chloro,

tetrahydroisothiazolyl,

tetrahydroisothiazolyl substituted twice by oxo, tetrahydro-1,2-thiazinyl,

tetrahydro-1,2-thiazinyl substituted twice by oxo,

- N(CH 3 )S(O) 2 CH 3 ,

- OS(O) 2 CH 3 ,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 5 substituents

independently selected from: fluoro, chloro, bromo, i odo, oxo, -S(O) 2 CH 3 , --CN, -OR69 and–NR66R67, where R 66 and R 67 are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 68 R 69 , where R 68 and R 69 are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, -OH, -OC1-5alkyl, -OC1-5alkyl substituted from 1 to 6 times by fluoro and–COOH.

This invention relates to novel compounds of Formula (VIIccr) and to the use of compounds of Formula (VIIccr) in the methods of the invention: wherein: R 70ccr is selected from:

ethyl,

ethyl substituted from 1 to 4 times by fluoro,

- NCH 3 , -SCH 3 ,

ethoxy,

methoxy,

phenyl,

furanyl,

cyclopropyl,

cyclopropyl substituted once or twice by fluoro;

R 77ccr is selected from:

phenyl,

phenyl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

--CN,

oxo,

C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 3 substituents independently selected from: fluoro, chloro, oxo, - OH, -NH 2 , -NHCH 3 , and–N(CH3)2, C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, bromo, i odo, oxo, -S(O) 2 CH 3 , --CN, -OR79a and – NR 76a R 77a ,

where R 76a and R 77a are independently selected from: hydrogen, -S(O)2CH3, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 78a R 79a , where R 78a and R 79a are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, tetrahydroisothiazolyl,

tetrahydroisothiazolyl substituted twice by oxo, tetrahydro-1,2-thiazinyl,

tetrahydro-1,2-thiazinyl substituted twice by oxo,

- N(CH 3 )S(O) 2 CH 3 ,

- N(CH 3 )S(O) 2 CFH 2 ,

- N(CH 3 )S(O) 2 CF 2 H,

- N(CH 3 )S(O) 2 CF 3 ,

- OS(O) 2 CH 3 ,

-S(O) 2 NH 2 ,

-S(O) 2 NHCH 3 , and –NR 80a R 81a where R 80a and R 81a are independently s elected form: hydrogen, -S(O) 2 CH 3 , phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -NH 2 , -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH,

dihydropyridinyl,

oxo-dihydropyridinyl,

tetrahydroisoquinolinyl,

tetrahydroisoquinolinyl substituted by–C(O)CH 3 ,

thiazolyl, and thiazolyl substituted by a substituent selected from: -C(O)CH 3 and - NHC(O)CH 3 ;

R 72ccr and R 73ccr are independently selected from:

hydrogen,

C 1-4 alkyl,

C 1-4 alkyl substituted with from 1 to 4 substituents

independently selected from: phenyl, morpholino, triazolyl, i midazolyl, -CH 2 CH 2 pyrrolidinyl, -OC(O)NH 2 , -OCH 2 CH 2 NH 2 , -ONHC(NH 2 )NH 2 , -NHCH 2 C(CH 3 ) 3 , -NOCH 3 , -NHOH, -NHCH 2 CH 2 F, -N(CH 3 )CH 2 CH 2 OCH 3 , -N(CH 2 CH 3 ) 2 , -NCH(CH 2 OH) 2 , -N(CH 2 CH 2 OH) 2 , -NHCH 2 CH 2 OH, -NHCH 2 CH 2 NH 2 , -N(CH 3 )CH 2 (CH 3 ) 2 CH 2 OH, -NHCH 2 CH 3 , -NHCH 2 CH 2 OCH 3 , -N(CH 3 )CH 2 CH 2 OH, -NHC(O)C(O)NH 2 , -N(CH 3 )CH 2 CH 2 CH 2 OH, -N(CH 3 )CH 2 CH(OH)CH 2 OH, -N(CH 3 )CH 2 CH 2 NH 2 , oxo, -NHCH 2 C(CH 3 ) 2 CH 2 OH, -OH, -NH 2 , -NHCH 3 , -NHCH 2 CH 2 CH 2 OH, -N(CH 3 ) 2 , -N(CH 3 )CH 2 CH 3 , -NHOC(CH 3 ) 2 NH 2 , -N(CH 3 )CH 2 cyclopropyl, -NHCH 2 cyclopropyl, -NHoxetanyl, -NCH 2 CH 2 triazole, piperazinyl, piperidinyl, pyrazolyl, azepinyl, azetidinyl, methoxy, and cyclopropylamino,

where said phenyl, morpholino, triazolyl, imidazolyl, azepinyl, azetidinyl, pyrrolidinyl piperazinyl, piperidinyl, oxetanyl, cyclopropyl, and pyrazolyl are optionally substituted with from 1 to 4 substituents independently selected from: methyl, fluoro, -NH 2 , - N(CH 3 ) 2 , hydroxymethyl, oxo, -OH, and–CH 2 NH 2 , cyclobutyl,

aminocyclobutyl,

tetrahydrofuran,

5-oxa-2azaspiro[3.4]octan, and

8-azabicyclo[3.2.1]octan, or

R 72ccr and R 73ccr are taken together with the nitrogen to which they are

attached, and optionally from 1 to 3 additional heteroatoms independently selected from O, N, and S, to form a heterocycloalkyl, to form a heterocycloalkyl selected from:

pyrrolidinyl,

pyrrolo[3,4-c]pyrazolyl,

piperidinyl,

1,4diazepanyl,

piperazinyl,

6,7-dihydro-triazolo[4,5-c]pyridinyl,

2,9-diazaspiro[5.5]undecanyl,

2,8-diazaspiro[4.5]decanyl,

octahydro-1H-pyrrolo[1,2a][1,4]diazepinyl, oxa-diazaspiro[4.5]decanyl,

oxazolyl,

morpholinyl, 1-oxa-6-azaspiro[3.4]octanyl,

2-oxa-6-azaspiro[3.4]octanyl,

1,7-diazaspiro[3.5]nonanyl,

2,7-diazaspiro[3.5]nonanyl,

2,6-diazaspiro[3.4]octanyl,

azetidinyl,

hexahydropyrrolo[3,4-b]oxazinyl,

dihydronaphthyridinyl,

diazabicycloheptanyl,

1,8-diazaspiro[4.5]decanyl, and

5-oxa-2-azaspiro[3.4]octanyl,

all of which are optionally substituted with from 1 to 5 substituents independently selected from: fluoro,

chloro,

oxo,

-OH,

- OP(O)(OH) 2 ,

-CN,

- CH 3 ,

- CH 2 OH,

methoxy,

- CH 2 CH 3 ,

- C(O)CH 3 ,

- C(O)NH 2 , -OCH 2 CH 2 OH,

- OCH 2 CH 2 NH 2 ,

- ONHC(NH)NH 2 ,

- OC(O)NH 2 ,

-Ooxetanyl, -CH 2 CH 2 OH,

- CH 2 CH 2 CH 2 OH, -CH 2 CH 2 CH 3 ,

- CH 2 CH 2 OCH 3 ,

- CH 2 CH(OH)CH 3 , -CH 2 CH(OH)CH 2 OH, -CH 2 C(O)OCH 3 ,

- CH 2 C(O)NH 2 ,

- C(O)CH(CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 NHCH 2 CH 3 , -CH 2 CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 NHCH 2 C(CH 3 ) 3 , -CH 2 CH 2 N(CH 3 )CH 2 OCH 3 , -C(CH 3 ) 2 CH 2 OH, -CH 2 C(CH 3 ) 2 OH, -CH 2 C(CH 3 ) 2 OCH 3 , -C(O)CH 2 OH,

- CH 2 isothiazolyl,

- CH 2 thiazolyl,

- CH 2 pyrazolyl,

- CH 2 imidazolyl,

- CH 2 pyridinyl,

-CH2oxazolyl, -CH 2 pyrrolyl,

- CH 2 pyrrolidinyl, -CH 2 isoxazoly,

- CH 2 furanyl,

- CH 2 CH 2morpholinyl , -CH 2 CH 2 pyrrolidinyl, -CH 2 CH 2 pyrrolidinylCH 3 , -CH 2 CH 2 CH 2 pyrrolidinyl, -C(O)phenyl,

-C(O)C(tetrahydropyranyl)NH 2 , -NH 2 ,

- NHCH 3 , -N(CH 3 ) 2 ,

- NHC(O)CH 3 ,

- NHCH(CH 3)2 ,

- NHCH 2 CHF 2 ,

- NHCH 2 C(CH 3)3 , -NHCH 2 CH(CH 3)2 ,

- NHCH 2 CH 2 OCH 3 ,

- NHCH 2 CH 2 OH,

- NHCH 2 CH 2 NH 2 ,

- NHCH 2 C(O)OH,

- NHC(O)CH 2 NH 2 ,

- NHC(O)CH 2 CH 2 CH 2 NH 2 , -NHCH 2 C(O)NH 2 , -NHCH 2 C(OH)(CH 3 ) 2 , -NHC(O)CH(CH 3 )NH 2 , -NHC(O)OCH(CH 3 )NH 2 , -NHC(O)CH(CH 3 ) 2 , -NHC(O)C(CH 3 ) 3 , -NHC(O)C(CH 3 ) 2 NH 2 , -NHC(O)CH 2 OH, -NHC(O)CH(CH 2 OH)NH 2 , -NHC(O)(oxetanyl)NH 2 , -NHC(O)OC(CH 3 ) 3 , -NHC(CH 3 ) 2 C(O)OCH 3 , -NHcyclopropyl, -NHoxetanyl,

- CH 2 NH 2 ,

- CH 2 CH 2 NH 2 ,

- CH 2 CH 2 CH 2 NH 2 , -CH 2 NHCH 2 C(CH 3 ) 3 , -CH 2 NHC(O)C(CH 3 ) 3 , -CH 2 NHC(O)CH 2 NH 2 , -CH 2 NHC(O)CH 2 OH, -CH 2 N(CH 3 ) 2 ,

- CH 2 NHCH 3 ,

- CH 2 N(CH 2 CH 3 ) 2 , -CH 2 CH 2 N(CH 3 ) 2 , -S(O) 2 CH 2 CH 3 ,

- S(O) 2 CH 2 CH 2 CH 3 , -S(O) 2 phenyl,

- S(O) 2 CH 3 ,

benzoyl,

benzylamino,

-propylpyrrolidinyl,

-methylcyclopropyl, cyclobutylamino,

c yclobutyl-N(CH 3 )-, piperidinyl,

imidazolyl,

morpholinyl,

morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinyl, pyrrolidinyl,

pyrrolidinylmethyl,

(methoxypyridinylmethyl)amino, methylpyrrolidinyl,

difluoropyrrolidinyl, dimethylpyrrolidinyl,

(methylcyclopropylmethyl)amino, hydroxymethylpyrrolidinyl, fluoropyrrolidinyl,

(fluorophenylmethyl)amino, piperazinylmethyl,

oxazolidinyl,

(methyloxetanylmethyl)amino, (methylcyclobutylmethyl)amino, oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl; provided that:

R 72ccr and R 73ccr are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (VIIccr), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (VIIccr), the compounds are in the form of a–C(O)CH(NH2)CH(CH3)2 prodrug.

Suitably in the compounds of Formula (VIIccr) neither R 72ccr nor R 73ccr is hydrogen. Suitably in the compounds of Formula (VIIccr) R 77ccr is phenyl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

--CN,

oxo,

C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, oxo, - OH, -NH 2 , -NHCH 3 , and–N(CH3)2,

tetrahydroisothiazolyl,

tetrahydroisothiazolyl substituted twice by oxo, tetrahydro-1,2-thiazinyl,

tetrahydro-1,2-thiazinyl substituted twice by oxo,

- N(CH 3 )S(O) 2 CH 3 ,

- OS(O) 2 CH 3 ,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 3 substituents independently selected from: fluoro, chloro, bromo, i odo, oxo, -S(O) 2 CH 3 , --CN, -OR79a and – NR 76a R 77a ,

where R 76a and R 77a are independently s elected from: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 78a R 79a , where R 78a and R 79a are independently selected from: h ydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH.

This invention relates to novel compounds of Formula (Qc) and to the use of compounds of Formula (Qc) in the methods of the invention:

wherein: R 70ca’’ is selected from:

ethyl, -OCH 3 ,

-CH 2 CF 3 , and

cyclopropyl;

R 77ca’’ is selected from:

phenyl,

phenyl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

-CN,

oxo,

C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, oxo, - OH, -NH 2 , -NHCH 3 , and–N(CH3)2,

C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, bromo, i odo, oxo, -S(O) 2 CH 3 , -CN, -OR79a’ and – NR 76a’ R 77a’ ,

where R 76a’ and R 77a’ are independently selected form: hydrogen, -S(O)2CH3, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 78a’ R 79a’ , where R 78a’ and R 79a’ are independently selected form: hydrogen, phenyl, C 1-5 alkyl and

C 1-5 alkyl substituted with from 1 to 4 substituentsindependently selected from: f luoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and –COOH,

tetrahydroisothiazolyl,

tetrahydroisothiazolyl substituted twice by oxo, tetrahydro-1,2-thiazinyl,

tetrahydro-1,2-thiazinyl substituted twice by oxo,

- N(CH 3 )S(O) 2 CFH 2 ,

- N(CH 3 )S(O) 2 CF 2 H,

- N(CH 3 )S(O) 2 CF 3 ,

- OS(O) 2 CH 3 ,

-S(O) 2 NH 2 , -S(O) 2 NHCH 3 , and –NR 80a’ R 81a’ where R 80a’ and R 81a’ are independently selected f orm: hydrogen, -S(O) 2 CH 3 , phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituentsindependently selected from: fluoro, oxo, -OH, - NH 2 , -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6

times by fluoro and–COOH, and

R 72ca’’ and R 73ca’’ are independently selected from:

hydrogen,

C 1-4 alkyl, C 1-4 alkyl substituted with from 1 to 4 substituents

independently selected from: phenyl, morpholino, triazolyl, i midazolyl, -CH 2 CH 2 pyrrolidinyl, -OC(O)NH 2 , -OCH 2 CH 2 NH 2 , -ONHC(NH 2 )NH 2 , -NHCH 2 C(CH 3 ) 3 , -NOCH 3 , -NHOH,

- NHCH 2 CH 2 F, -N(CH 3 )CH 2 CH 2 OCH 3 , -N(CH 2 CH 3 ) 2 ,

- NCH(CH 2 OH) 2 , -N(CH 2 CH 2 OH) 2 , -NHCH 2 CH 2 OH, -NHCH 2 CH 2 NH 2 , -N(CH 3 )CH 2 (CH 3 ) 2 CH 2 OH, -NHCH 2 CH 3 , -NHCH 2 CH 2 OCH 3 , -N(CH 3 )CH 2 CH 2 OH, -NHC(O)C(O)NH 2 , -N(CH 3 )CH 2 CH 2 CH 2 OH, -N(CH 3 )CH 2 CH(OH)CH 2 OH,

- N(CH 3 )CH 2 CH 2 NH 2 , oxo, -NHCH 2 C(CH 3 ) 2 CH 2 OH, -OH, -NH 2 , -NHCH 3 , -NHCH 2 CH 2 CH 2 OH, -N(CH 3 ) 2 , -N(CH 3 )CH 2 CH 3 , -NHOC(CH 3 ) 2 NH 2 , -N(CH 3 )CH 2 cyclopropyl, -NHCH 2 cyclopropyl, -NHoxetanyl, -NCH 2 CH 2 triazole, piperazinyl, piperidinyl, pyrazolyl, azepinyl, azetidinyl, methoxy, and cyclopropylamino,

where said phenyl, morpholino, triazolyl, imidazolyl, azepinyl, azetidinyl, pyrrolidinyl piperazinyl, piperidinyl, oxetanyl, cyclopropyl, and pyrazolyl are optionally substituted with from 1 to 4 substituents independently selected from: methyl, fluoro, -NH 2 , - N(CH 3 ) 2 , hydroxymethyl, oxo, -OH, and–CH 2 NH 2 , cyclobutyl,

aminocyclobutyl,

tetrahydrofuran,

5-oxa-2azaspiro[3.4]octan, and

8-azabicyclo[3.2.1]octan, or

R 72a’’ and R 73a’’ are taken together with the nitrogen to which they are

attached, and optionally from 1 to 3 additional heteroatoms independently selected from O, N, and S, to form a heterocycloalkyl selected from:

pyrrolidinyl,

pyrrolo[3,4-c]pyrazolyl,

piperidinyl,

1,4diazepanyl,

piperazinyl,

6,7-dihydro-triazolo[4,5-c]pyridinyl,

2,9-diazaspiro[5.5]undecanyl,

2,8-diazaspiro[4.5]decanyl,

octahydro-1H-pyrrolo[1,2a][1,4]diazepinyl, oxa-diazaspiro[4.5]decanyl,

oxazolyl,

morpholinyl,

1-oxa-6-azaspiro[3.4]octanyl,

2-oxa-6-azaspiro[3.4]octanyl,

1,7-diazaspiro[3.5]nonanyl,

2,7-diazaspiro[3.5]nonanyl,

2,6-diazaspiro[3.4]octanyl,

azetidinyl,

hexahydropyrrolo[3,4-b]oxazinyl,

dihydronaphthyridinyl,

diazabicycloheptanyl,

1,8-diazaspiro[4.5]decanyl, and

5-oxa-2-azaspiro[3.4]octanyl,

all of which are optionally substituted with from 1 to 5 substituents independently selected from: fluoro,

chloro,

oxo,

-OH,

- OP(O)(OH) 2 ,

-CN,

- CH 3 ,

- CH 2 OH, methoxy,

- CH 2 CH 3 ,

- C(O)CH 3 ,

- C(O)NH 2 ,

- OCH 2 CH 2 OH,

- OCH 2 CH 2 NH 2 ,

- ONHC(NH)NH 2 ,

- OC(O)NH 2 ,

-Ooxetanyl,

- CH 2 CH 2 OH,

- CH 2 CH 2 CH 2 OH, -CH 2 CH 2 CH 3 ,

- CH 2 CH 2 OCH 3 ,

- CH 2 CH(OH)CH 3 , -CH 2 CH(OH)CH 2 OH, -CH 2 C(O)OCH 3 ,

- CH 2 C(O)NH 2 ,

- C(O)CH(CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 NHCH 2 CH 3 , -CH 2 CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 NHCH 2 C(CH 3 ) 3 , -CH 2 CH 2 N(CH 3 )CH 2 OCH 3 , -C(CH 3 ) 2 CH 2 OH, -CH 2 C(CH 3 ) 2 OH, -CH 2 C(CH 3 ) 2 OCH 3 , -C(O)CH 2 OH, -CH 2 isothiazolyl,

- CH 2 thiazolyl,

- CH 2 pyrazolyl,

- CH 2 imidazolyl,

- CH 2 pyridinyl,

- CH 2 oxazolyl,

- CH 2 pyrrolyl,

- CH 2 pyrrolidinyl,

- CH 2 isoxazoly,

- CH 2 furanyl, -CH 2 CH 2morpholinyl , -CH 2 CH 2 pyrrolidinyl, -CH 2 CH 2 pyrrolidinylCH 3 , -CH 2 CH 2 CH 2 pyrrolidinyl, -C(O)phenyl,

-C(O)C(tetrahydropyranyl)NH 2 , -NH 2 ,

- NHCH 3 ,

- N(CH 3 ) 2 ,

- NHC(O)CH 3 ,

- NHCH(CH 3)2 ,

- NHCH 2 CHF 2 , -NHCH 2 C(CH 3)3 , -NHCH 2 CH(CH 3)2 , -NHCH 2 CH 2 OCH 3 , -NHCH 2 CH 2 OH, -NHCH 2 CH 2 NH 2 , -NHCH 2 C(O)OH, -NHC(O)CH 2 NH 2 , -NHC(O)CH 2 CH 2 CH 2 NH 2 , -NHCH 2 C(O)NH 2 , -NHCH 2 C(OH)(CH 3 ) 2 , -NHC(O)CH(CH 3 )NH 2 , -NHC(O)OCH(CH 3 )NH 2 , -NHC(O)CH(CH 3 ) 2 , -NHC(O)C(CH 3 ) 3 , -NHC(O)C(CH 3 ) 2 NH 2 , -NHC(O)CH 2 OH, -NHC(O)CH(CH 2 OH)NH 2 , -NHC(O)(oxetanyl)NH 2 , -NHC(O)OC(CH 3 ) 3 , -NHC(CH 3 ) 2 C(O)OCH 3 , -NHcyclopropyl,

-NHoxetanyl,

- CH 2 NH 2 ,

- CH 2 CH 2 NH 2 ,

- CH 2 CH 2 CH 2 NH 2 , -CH 2 NHCH 2 C(CH 3 ) 3 , -CH 2 NHC(O)C(CH 3 ) 3 , -CH 2 NHC(O)CH 2 NH 2 , -CH 2 NHC(O)CH 2 OH, -CH 2 N(CH 3 ) 2 ,

- CH 2 NHCH 3 ,

- CH 2 N(CH 2 CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 ,

- S(O) 2 CH 2 CH 3 ,

- S(O) 2 CH 2 CH 2 CH 3 , -S(O) 2 phenyl,

- S(O) 2 CH 3 ,

benzoyl,

benzylamino,

-propylpyrrolidinyl,

-methylcyclopropyl, cyclobutylamino,

c yclobutyl-N(CH 3 )-, piperidinyl,

imidazolyl,

morpholinyl,

morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinyl, pyrrolidinyl,

pyrrolidinylmethyl,

(methoxypyridinylmethyl)amino, methylpyrrolidinyl, difluoropyrrolidinyl, dimethylpyrrolidinyl,

(methylcyclopropylmethyl)amino,

hydroxymethylpyrrolidinyl,

fluoropyrrolidinyl,

(fluorophenylmethyl)amino,

piperazinylmethyl,

oxazolidinyl,

(methyloxetanylmethyl)amino,

(methylcyclobutylmethyl)amino,

oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl;

provided that:

R 72a’’ and R 73a’’ are not both hydrogen; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (Qc), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (Qc), the compounds are in the form of a –C(O)CH(NH 2 )CH(CH 3 ) 2 prodrug.

Suitably in the compounds of Formula (Qc) neither R 72a’’ nor R 73a’’ is hydrogen. This invention relates to novel compounds of Formula (Qc1) and to the use of compounds of Formula (Qc1) in the methods of the invention:

wherein: R 70ca1 is selected from:

ethyl,

-OCH 3 ,

-CH 2 CF 3 , and

cyclopropyl;

R 77ca1’’ is selected from:

phenyl,

phenyl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

--CN,

oxo,

C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, oxo, - OH, -NH 2 , -NHCH 3 , and–N(CH3)2,

C 1-6 alkyl,

C1-6alkyl substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, bromo, i odo, oxo, -S(O) 2 CH 3 , --CN, -OR79a’ and – NR 76a’ R 77a’ ,

where R 76a’ and R 77a’ are independently s elected form: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 78a R 79a , where R 78a’ and R 79a’ are independently selected f orm: hydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituentsindependently selected from: f luoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and –COOH,

tetrahydroisothiazolyl,

tetrahydroisothiazolyl substituted twice by oxo, tetrahydro-1,2-thiazinyl,

tetrahydro-1,2-thiazinyl substituted twice by oxo,

- OS(O) 2 CH 3 ,

- N(CH 3 )S(O) 2 CH 3 ,

- N(CH 3 )S(O) 2 CFH 2 ,

- N(CH 3 )S(O) 2 CF 2 H,

- N(CH 3 )S(O) 2 CF 3 ,

-S(O)2NH2, -S(O) 2 NHCH 3 , and –NR 80a’ R 81a’ where R 80a’ and R 81a’ are independently s elected form: hydrogen, -S(O) 2 CH 3 , phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -NH 2 , -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, and R 72ca1’’ and R 73ca1’’ are independently selected from: C1-4alkyl, C 1-4 alkyl substituted with from 1 to 4 substituents

independently selected from: phenyl, morpholino, triazolyl, i midazolyl, -CH 2 CH 2 pyrrolidinyl, -OC(O)NH 2 , -OCH 2 CH 2 NH 2 , -ONHC(NH 2 )NH 2 , -NHCH 2 C(CH 3 ) 3 , -NOCH 3 , -NHOH,

- NHCH 2 CH 2 F, -N(CH 3 )CH 2 CH 2 OCH 3 , -N(CH 2 CH 3 ) 2 ,

- NCH(CH 2 OH) 2 , -N(CH 2 CH 2 OH) 2 , -NHCH 2 CH 2 OH, -NHCH 2 CH 2 NH 2 , -N(CH 3 )CH 2 (CH 3 ) 2 CH 2 OH, -NHCH 2 CH 3 , -NHCH 2 CH 2 OCH 3 , -N(CH 3 )CH 2 CH 2 OH, -NHC(O)C(O)NH 2 , -N(CH 3 )CH 2 CH 2 CH 2 OH, -N(CH 3 )CH 2 CH(OH)CH 2 OH,

- N(CH 3 )CH 2 CH 2 NH 2 , oxo, -NHCH 2 C(CH 3 ) 2 CH 2 OH, -OH, -NH 2 , -NHCH 3 , -NHCH 2 CH 2 CH 2 OH, -N(CH 3 ) 2 , -N(CH 3 )CH 2 CH 3 , -NHOC(CH 3 ) 2 NH 2 , -N(CH 3 )CH 2 cyclopropyl, -NHCH 2 cyclopropyl, -NHoxetanyl, -NCH 2 CH 2 triazole, piperazinyl, piperidinyl, pyrazolyl, azepinyl, azetidinyl, methoxy, and cyclopropylamino,

where said phenyl, morpholino, triazolyl, imidazolyl, azepinyl, azetidinyl, pyrrolidinyl piperazinyl, piperidinyl, oxetanyl, cyclopropyl, and pyrazolyl are optionally substituted with from 1 to 4 substituents independently selected from: methyl, fluoro, -NH 2 , - N(CH 3 ) 2 , hydroxymethyl, oxo, -OH, and–CH 2 NH 2 , cyclobutyl,

aminocyclobutyl,

tetrahydrofuran,

5-oxa-2azaspiro[3.4]octan, and

8-azabicyclo[3.2.1]octan, or

R 72ca1’’ and R 73ca1’’ are taken together with the nitrogen to which they are attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl selected from: pyrrolidinyl,

pyrrolo[3,4-c]pyrazolyl,

piperidinyl,

1,4diazepanyl,

piperazinyl,

6,7-dihydro-triazolo[4,5-c]pyridinyl,

2,9-diazaspiro[5.5]undecanyl,

2,8-diazaspiro[4.5]decanyl,

octahydro-1H-pyrrolo[1,2a][1,4]diazepinyl, oxa-diazaspiro[4.5]decanyl,

oxazolyl,

morpholinyl,

1-oxa-6-azaspiro[3.4]octanyl,

2-oxa-6-azaspiro[3.4]octanyl,

1,7-diazaspiro[3.5]nonanyl,

2,7-diazaspiro[3.5]nonanyl,

2,6-diazaspiro[3.4]octanyl,

azetidinyl,

hexahydropyrrolo[3,4-b]oxazinyl,

dihydronaphthyridinyl,

diazabicycloheptanyl,

1,8-diazaspiro[4.5]decanyl, and

5-oxa-2-azaspiro[3.4]octanyl,

all of which are optionally substituted with from 1 to 5 substituents independently selected from: fluoro,

chloro,

oxo,

-OH,

--CN,

- CH 3 ,

- CH 2 OH,

methoxy,

- CH 2 CH 3 , -C(O)CH 3 ,

- C(O)NH 2 ,

- OCH 2 CH 2 OH,

- OCH 2 CH 2 NH 2 ,

- ONHC(NH)NH 2 ,

- OC(O)NH 2 ,

-Ooxetanyl,

- CH 2 CH 2 OH,

- CH 2 CH 2 CH 2 OH, -CH 2 CH 2 CH 3 ,

- CH 2 CH 2 OCH 3 ,

- CH 2 CH(OH)CH 3 , -CH 2 CH(OH)CH 2 OH, -CH 2 C(O)OCH 3 ,

- CH 2 C(O)NH 2 ,

- C(O)CH(CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 NHCH 2 CH 3 , -CH 2 CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 NHCH 2 C(CH 3 ) 3 , -CH 2 CH 2 N(CH 3 )CH 2 OCH 3 , -C(CH 3 ) 2 CH 2 OH, -CH 2 C(CH 3 ) 2 OH, -CH 2 C(CH 3 ) 2 OCH 3 , -C(O)CH 2 OH,

- CH 2 isothiazolyl, -CH 2 thiazolyl,

- CH 2 pyrazolyl,

- CH 2 imidazolyl,

- CH 2 pyridinyl,

- CH 2 oxazolyl,

- CH 2 pyrrolyl,

- CH 2 pyrrolidinyl,

- CH 2 isoxazoly,

- CH 2 furanyl,

- CH 2 CH 2morpholinyl , -CH 2 CH 2 pyrrolidinyl, -CH 2 CH 2 pyrrolidinylCH 3 , -CH 2 CH 2 CH 2 pyrrolidinyl, -C(O)phenyl,

-C(O)C(tetrahydropyranyl)NH 2 , -NH 2 ,

- NHCH 3 ,

- N(CH 3 ) 2 ,

- NHC(O)CH 3 ,

- NHCH(CH 3)2 ,

- NHCH 2 CHF 2 ,

- NHCH 2 C(CH 3)3 , -NHCH 2 CH(CH 3)2 , -NHCH 2 CH 2 OCH 3 , -NHCH 2 CH 2 OH, -NHCH 2 CH 2 NH 2 , -NHCH 2 C(O)OH, -NHC(O)CH 2 NH 2 , -NHC(O)CH 2 CH 2 CH 2 NH 2 , -NHCH 2 C(O)NH 2 , -NHCH 2 C(OH)(CH 3 ) 2 , -NHC(O)CH(CH 3 )NH 2 , -NHC(O)OCH(CH 3 )NH 2 , -NHC(O)CH(CH 3 ) 2 , -NHC(O)C(CH 3 ) 3 , -NHC(O)C(CH 3 ) 2 NH 2 , -NHC(O)CH 2 OH, -NHC(O)CH(CH 2 OH)NH 2 , -NHC(O)(oxetanyl)NH 2 , -NHC(O)OC(CH 3 ) 3 , -NHC(CH 3 ) 2 C(O)OCH 3 , -NHcyclopropyl,

-NHoxetanyl,

- CH 2 NH 2 ,

- CH 2 CH 2 NH 2 ,

- CH 2 CH 2 CH 2 NH 2 , -CH 2 NHCH 2 C(CH 3 ) 3 , -CH 2 NHC(O)C(CH 3 ) 3 , -CH 2 NHC(O)CH 2 NH 2 , -CH 2 NHC(O)CH 2 OH, -CH 2 N(CH 3 ) 2 ,

- CH 2 NHCH 3 ,

- CH 2 N(CH 2 CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 ,

- S(O) 2 CH 2 CH 3 ,

- S(O) 2 CH 2 CH 2 CH 3 , -S(O) 2 phenyl,

- S(O) 2 CH 3 ,

benzoyl,

benzylamino,

3-pyrrolidinylpropyl, 2-cyclopropylmethyl, cyclobutylamino, cyclobutyl-N(CH 3 )-, piperidinyl,

imidazolyl,

morpholinyl,

morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinyl, pyrrolidinyl,

pyrrolidinylmethyl, methoxypyridinylmethylamino, methylpyrrolidinyl, difluoropyrrolidinyl, dimethylpyrrolidinyl, methylcyclopropylmethylamino,

hydroxymethylpyrrolidinyl,

fluoropyrrolidinyl,

fluorophenylmethylamino,

piperazinylmethyl,

oxazolidinyl,

methyloxetanmethylamino,

methylcyclobutylmethylamino,

oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl;

provided that:

R 72ca1’’ and R 73ca1’’ are not both unsubstituted alkyl; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (Qc1), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (Qc1), the compounds are in the form of a –C(O)CH(NH 2 )CH(CH 3 ) 2 prodrug. This invention relates to novel compounds of Formula (Qc2) and to the use of compounds of Formula (Qc2) in the methods of the invention:

wherein: R 70ca2’’ is selected from:

ethyl,

-OCH 3 , -CH 2 CF 3 , and

cyclopropyl;

R 77ca2’’ is selected from:

phenyl,

phenyl substituted with from 1 to 4 substituents independently selected from:

fluoro,

chloro,

--CN,

oxo,

C 1-4 alkoxy,

C 1-4 alkoxy substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, oxo, - OH, -NH 2 , -NHCH 3 , and–N(CH3)2, C 1-6 alkyl,

C 1-6 alkyl substituted with from 1 to 3 substituents

independently selected from: fluoro, chloro, bromo, i odo, oxo, -S(O) 2 CH 3 , --CN, -OR79a’ and – NR 76a’ R 77a’ ,

where R 76a’ and R 77a’ are independently s elected form: hydrogen, -S(O) 2 CH 3 , C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituents independently selected f rom: fluoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro,–COOH and–NR 78a’ R 79a’ , where R 78a’ and R 79a’ are independently selected f orm: hydrogen, phenyl, C 1-5 alkyl and C 1-5 alkyl substituted with from 1 to 4 substituentsindependently selected from: f luoro, oxo, -OH, -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and –COOH,

tetrahydroisothiazolyl,

tetrahydroisothiazolyl substituted twice by oxo, tetrahydro-1,2-thiazinyl,

tetrahydro-1,2-thiazinyl substituted twice by oxo,

- N(CH 3 )S(O) 2 CH 3 ,

- N(CH 3 )S(O) 2 CFH 2 ,

- N(CH 3 )S(O) 2 CF 2 H,

- N(CH 3 )S(O) 2 CF 3 ,

- OS(O) 2 CH 3 ,

-S(O) 2 NH 2 , -S(O) 2 NHCH 3 , and –NR 80a’ R 81a’ where R 80a’ and R 81a’ are independently s elected form: hydrogen, -S(O) 2 CH 3 , phenyl, C1-5alkyl and C1-5alkyl substituted with from 1 to 4 substituents independently selected from: fluoro, oxo, - OH, -NH 2 , -OC 1-5 alkyl, -OC 1-5 alkyl substituted from 1 to 6 times by fluoro and–COOH, and

R 72ca2’’ and R 73ca2’’ are taken together with the nitrogen to which they are

attached, and optionally from 1 to 3 additional heteroatoms, to form a heterocycloalkyl selected from:

pyrrolidinyl,

pyrrolo[3,4-c]pyrazolyl,

piperidinyl,

1,4diazepanyl, piperazinyl,

6,7-dihydro-triazolo[4,5-c]pyridinyl,

2,9-diazaspiro[5.5]undecanyl,

2,8-diazaspiro[4.5]decanyl,

octahydro-1H-pyrrolo[1,2a][1,4]diazepinyl, oxa-diazaspiro[4.5]decanyl,

oxazolyl,

morpholinyl,

1-oxa-6-azaspiro[3.4]octanyl,

2-oxa-6-azaspiro[3.4]octanyl,

1,7-diazaspiro[3.5]nonanyl,

2,7-diazaspiro[3.5]nonanyl,

2,6-diazaspiro[3.4]octanyl,

azetidinyl,

hexahydropyrrolo[3,4-b]oxazinyl,

dihydronaphthyridinyl,

diazabicycloheptanyl,

1,8-diazaspiro[4.5]decanyl, and

5-oxa-2-azaspiro[3.4]octanyl,

all of which are optionally substituted with from 1 to 5 substituents independently selected from: fluoro,

chloro,

oxo,

-OH,

--CN,

- CH 3, - CH 2 OH,

methoxy,

- CH 2 CH 3 ,

- C(O)CH 3 ,

- C(O)NH 2 , -OCH 2 CH 2 OH,

- OCH 2 CH 2 NH 2 ,

- ONHC(NH)NH 2 ,

- OC(O)NH 2 ,

-Ooxetanyl,

- CH 2 CH 2 OH,

- CH 2 CH 2 CH 2 OH, -CH 2 CH 2 CH 3 ,

- CH 2 CH 2 OCH 3 ,

- CH 2 CH(OH)CH 3 , -CH 2 CH(OH)CH 2 OH, -CH 2 C(O)OCH 3 ,

- CH 2 C(O)NH 2 ,

- C(O)CH(CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 NHCH 2 CH 3 , -CH 2 CH 2 CH 2 N(CH 3 ) 2 , -CH 2 CH 2 NHCH 2 C(CH 3 ) 3 , -CH 2 CH 2 N(CH 3 )CH 2 OCH 3 , -C(CH 3 ) 2 CH 2 OH, -CH 2 C(CH 3 ) 2 OH, -CH 2 C(CH 3 ) 2 OCH 3 , -C(O)CH 2 OH,

- CH 2 isothiazolyl, -CH 2 thiazolyl,

- CH 2 pyrazolyl, -CH 2 imidazolyl,

- CH 2 pyridinyl,

- CH 2 oxazolyl,

- CH 2 pyrrolyl,

- CH 2 pyrrolidinyl,

- CH 2 isoxazoly,

- CH 2 furanyl,

- CH 2 CH 2morpholinyl , -CH 2 CH 2 pyrrolidinyl, -CH 2 CH 2 pyrrolidinylCH 3 , -CH 2 CH 2 CH 2 pyrrolidinyl, -C(O)phenyl,

-C(O)C(tetrahydropyranyl)NH 2 , -NH 2 ,

- NHCH 3 , -N(CH 3 ) 2 ,

- NHC(O)CH 3 ,

- NHCH(CH 3)2 ,

- NHCH 2 CHF 2 ,

- NHCH 2 C(CH 3)3 ,

- NHCH 2 CH(CH 3)2 ,

- NHCH 2 CH 2 OCH 3 , -NHCH 2 CH 2 OH, -NHCH 2 CH 2 NH 2 , -NHCH 2 C(O)OH, -NHC(O)CH 2 NH 2 , -NHC(O)CH 2 CH 2 CH 2 NH 2 , -NHCH 2 C(O)NH 2 , -NHCH 2 C(OH)(CH 3 ) 2 , -NHC(O)CH(CH 3 )NH 2 , -NHC(O)OCH(CH 3 )NH 2 , -NHC(O)CH(CH 3 ) 2 , -NHC(O)C(CH 3 ) 3 , -NHC(O)C(CH 3 ) 2 NH 2 , -NHC(O)CH 2 OH, -NHC(O)CH(CH 2 OH)NH 2 , -NHC(O)(oxetanyl)NH 2 , -NHC(O)OC(CH 3 ) 3 , -NHC(CH 3 ) 2 C(O)OCH 3 , -NHcyclopropyl,

-NHoxetanyl,

- CH 2 NH 2 ,

- CH 2 CH 2 NH 2 , -CH 2 CH 2 CH 2 NH 2 , -CH 2 NHCH 2 C(CH 3 ) 3 , -CH 2 NHC(O)C(CH 3 ) 3 , -CH 2 NHC(O)CH 2 NH 2 , -CH 2 NHC(O)CH 2 OH, -CH 2 N(CH 3 ) 2 , -CH 2 NHCH 3 ,

- CH 2 N(CH 2 CH 3 ) 2 ,

- CH 2 CH 2 N(CH 3 ) 2 ,

- S(O) 2 CH 2 CH 3 ,

- S(O) 2 CH 2 CH 2 CH 3 , -S(O) 2 phenyl,

- S(O) 2 CH 3 ,

benzoyl,

benzylamino,

3-pyrrolidinylpropyl,

2-cyclopropylmethyl, cyclobutylamino, cyclobutyl-N(CH 3 )-, piperidinyl,

imidazolyl,

morpholinyl,

morpholinylmethyl, methylpiperazinylmethyl, methylpiperazinyl, pyrrolidinyl,

pyrrolidinylmethyl, methoxypyridinylmethylamino, methylpyrrolidinyl, difluoropyrrolidinyl, dimethylpyrrolidinyl, methylcyclopropylmethylamino, hydroxymethylpyrrolidinyl, fluoropyrrolidinyl, fluorophenylmethylamino,

piperazinylmethyl,

oxazolidinyl,

methyloxetanmethylamino,

methylcyclobutylmethylamino,

oxoimidazolidinyl, and

2-hydroxyethylpiperidinyl; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably in the compounds of Formula (Qc2), the compounds are in the form of a phosphate prodrug.

Suitably in the compounds of Formula (Qc2), the compounds are in the form of a –C(O)CH(NH 2 )CH(CH 3 ) 2 prodrug.

In an embodiment, X 51a is selected from: --CN, fluoro and chloro. In an embodiment, X 52a is selected from: --CN, fluoro and chloro. In an embodiment, X 51a is --CN. In an embodiment, X 52a is --CN.

In an embodiment, Y 5a is selected from: S and NH. In an embodiment, Y 5a is S. In an embodiment, Y 5bbr is S.

I n an embodiment, R50a is selected from: C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro and chloro, and cycloalkyl. In an embodiment, R 50a is selected from ethyl, cyclopropyl and 2,2,2,trifluoroethyl. In an embodiment, R 50a is ethyl.

I n an embodiment, R50bbr is selected from: C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro and chloro, and cycloalkyl. In an embodiment, R 50bbr is selected from ethyl, cyclopropyl and 2,2,2,trifluoroethyl. In an embodiment, R 50bbr is ethyl. In an embodiment, R50aar is selected from: phenyl, furanyl, C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro and chloro, and cycloalkyl. In an embodiment, R 50aar is selected from phenyl, furanyl, ethyl, cyclopropyl and 2,2,2,trifluoroethyl. In an embodiment, R 50aar is ethyl. In an embodiment, R 50aar is phenyl. In an embodiment, R 50aar is furanyl.

I n an embodiment R51a is selected from: hydrogen, C 1-6 alkyl, aryl, chlorophenyl and heteroaryl. In an embodiment R 51a is selected from: hydrogen, methyl, phenyl, chlorophenyl and pyridine. In an embodiment R 51a is phenyl. In an embodiment R 51a is hydrogen.

I n an embodiment R51bbr is selected from: hydrogen, C 1-6 alkyl, aryl, chlorophenyl and heteroaryl. In an embodiment R 51bbr is selected from: hydrogen, methyl, phenyl, chlorophenyl, piperidinyl and pyridinyl. In an embodiment R 51bbr is phenyl. In an embodiment R 51bbr is pyridinyl.

In an embodiment R 52a is selected from: -C(O)NH 2 and

phenylCH 2 NHC(O)CH 3 . In an embodiment R52a is -C(O)NH 2 . In an embodiment R52a is–phenylCH 2 NHC(O)CH 3 .

In an embodiment R 53a and R 54a are independently selected from: hydrogen, methyl, morpholinethyl, methoxyethyl, oxaazaspiro[3.4]octan, 5-oxa-2-azaspiro[3.4]octan, aminoethyl, amino-2-oxoethyl and hydroxyethyl.

In an embodiment R 53a and R 54a are taken together with the nitrogen to which they are attached to form: pyrrolidinyl, hydroxypyrrolidinyl, piperidinyl, hydroxypiperidinyl, 1,4- diazepanyl, methyl-1,4-diazepanyl, methoxyethyl-1,4-diazepanyl, hydroxypropyl-1,4- diazepanyl, methyl-1,4-diazepanacetate, (methyl)oxo-1,4-diazepanyl, (methyl)oxopiperazinyl, propylpiperazinyl, aminopyrrolidinyl, oxo-1,4-diazepanyl, piperidinylpiperazinyl, hydroxymethylpiperazinyl, oxopiperazinyl, morpholinpiperidinyl, hydroxyethyl1,4diazepanyl, dimethylaminopropylpiperazinyl, pyrrolidinpiperidinyl, piperidinpiperidinyl, pyrrolidinpropyl-1,4-diazepanyl, methylpiperazinyl, dimethylaminopiperidinyl, dimethylpiperazinyl, dimethylmorpholinyl, (aminomethyl)hydroxypiperidinyl, aminopiperidinyl, methylaminopiperidinyl, piperazinyl, aminoethylpiperazinyl, ethylpiperazinyl, morpholinmethylpiperidinyl, aminopropylpiperazinyl, methylpiperazinmethylpiperidinyl, pyrrolidinmethylpiperidinyl, methylpiperazinpiperidinyl, ethyl1,4diazepanyl, imidazolidinpiperidinyl, oxoimidazolidinpiperidinyl, propy-l1,4-diazepanyl, azetidinyl, methoxyazetidinyl, acetylpiperazinyl, hydroxyethylpiperazinyl, morpholinyl, 2-methylpropanoylpiperazinyl, ethanesulfonylpiperazinyl, methanesulfonylpiperazinyl, benzoylpiperazinyl, oxopiperidinyl, hydroxyethylpiperidinpiperidinyl, hydroxymethylmorpholinyl or difluoropiperidinyl,

In an embodiment R 53 and R 54 are taken together with the nitrogen to which they are attached to form: diazaspiroundecanyl, 2,9-diazaspiro[5.5]undecanyl, diazaspirodecanyl, 2,8-diazaspiro[4.5]decanyl, hexahydropyrrolo-1,4-diazepanyl, methyl- 2,9-diazaspiro[5.5]undecanyl, cyclopropylmethyl-2,9-diazaspiro[5.5]undecanyl, oxaazaspirooctanyl, oxaazaspiro[3.4]octanyl, diazaspirononanyl, diazaspiro[3.5]nonanyl, 1,7-diazaspiro[3.5]nonanyl, 2,7-diazaspiro[3.5]nonanyl, diazaspirooctanyl, diazaspiro[3.4]octanyl, 2,6-diazaspiro[3.4]octanyl, methanesulfonyl-1,8- diazaspiro[4.5]decanyl, azabicyclooctanyl, 8-azabicyclo[3.2.1]octanyl, 4-amino-4- methylpiperidin-1-yl, NH 2 CH 2 C(O)NH-piperidinyl, NH 2 CH(CH 3 )C(O)NH-piperidinyl, 3- aminooxetane-3-carbonyl)piperazinyl, 4-amino-(piperidin-4-yl)tetrahydro-2H-pyran-4- carboxamide, 4-amino-(piperazin-4-yl)tetrahydro-2H-pyran-4-carboxamide, hydroxyethyl- 1,4-diazepanyl, aminopiperidinyl, hydroxyazetidinyl, hydroxypyrrolidinyl or hydroxyethoxypiperidinyl.

In an embodiment R 53bbr and R 54bbr are independently selected from: hydrogen, methyl, morpholinethyl, methoxyethyl, oxaazaspiro[3.4]octan, 5-oxa-2-azaspiro[3.4]octan, aminoethyl, amino-2-oxoethyl and hydroxyethyl.

In an embodiment R 53bbr and R 54bbr are taken together with the nitrogen to which they are attached to form: pyrrolidinyl, hydroxypyrrolidinyl, piperidinyl, hydroxypiperidinyl, 1,4-diazepanyl, methyl-1,4-diazepanyl, methoxyethyl-1,4-diazepanyl, hydroxypropyl-1,4- diazepanyl, methyl-1,4-diazepanacetate, (methyl)oxo-1,4-diazepanyl, (methyl)oxopiperazinyl, propylpiperazinyl, aminopyrrolidinyl, oxo-1,4-diazepanyl, piperidinylpiperazinyl, hydroxymethylpiperazinyl, oxopiperazinyl, morpholinpiperidinyl, hydroxyethyl1,4diazepanyl, dimethylaminopropylpiperazinyl, pyrrolidinpiperidinyl, piperidinpiperidinyl, pyrrolidinpropyl-1,4-diazepanyl, methylpiperazinyl, dimethylaminopiperidinyl, dimethylpiperazinyl, dimethylmorpholinyl, (aminomethyl)hydroxypiperidinyl, aminopiperidinyl, methylaminopiperidinyl, piperazinyl, aminoethylpiperazinyl, ethylpiperazinyl, morpholinmethylpiperidinyl, aminopropylpiperazinyl, methylpiperazinmethylpiperidinyl, pyrrolidinmethylpiperidinyl, methylpiperazinpiperidinyl, ethyl1,4diazepanyl, imidazolidinpiperidinyl, oxoimidazolidinpiperidinyl, propy-l1,4-diazepanyl, azetidinyl, methoxyazetidinyl, acetylpiperazinyl, hydroxyethylpiperazinyl, morpholinyl, 2-methylpropanoylpiperazinyl, ethanesulfonylpiperazinyl, methanesulfonylpiperazinyl, benzoylpiperazinyl, oxopiperidinyl, hydroxyethylpiperidinpiperidinyl, hydroxymethylmorpholinyl or difluoropiperidinyl,

In an embodiment R 53bbr and R 54bbr are taken together with the nitrogen to which they are attached to form: diazaspiroundecanyl, 2,9-diazaspiro[5.5]undecanyl, diazaspirodecanyl, 2,8-diazaspiro[4.5]decanyl, hexahydropyrrolo-1,4-diazepanyl, methyl- 2,9-diazaspiro[5.5]undecanyl, cyclopropylmethyl-2,9-diazaspiro[5.5]undecanyl, oxaazaspirooctanyl, oxaazaspiro[3.4]octanyl, diazaspirononanyl, diazaspiro[3.5]nonanyl, 1,7-diazaspiro[3.5]nonanyl, 2,7-diazaspiro[3.5]nonanyl, diazaspirooctanyl, diazaspiro[3.4]octanyl, 2,6-diazaspiro[3.4]octanyl, methanesulfonyl-1,8- diazaspiro[4.5]decanyl, azabicyclooctanyl, 8-azabicyclo[3.2.1]octanyl, 4-amino-4- methylpiperidin-1-yl, NH 2 CH 2 C(O)NH-piperidinyl, NH 2 CH(CH 3 )C(O)NH-piperidinyl, 3- aminooxetane-3-carbonyl)piperazinyl, 4-amino-(piperidin-4-yl)tetrahydro-2H-pyran-4- carboxamide, 4-amino-(piperazin-4-yl)tetrahydro-2H-pyran-4-carboxamide, hydroxyethyl- 1,4-diazepanyl, aminopiperidinyl, hydroxyazetidinyl, hydroxypyrrolidinyl or hydroxyethoxypiperidinyl. In an embodiment, X 41ccr is selected from: --CN, fluoro and chloro. In an embodiment, X 42ccr is selected from: --CN, fluoro and chloro. In an embodiment, X 41ccr is --CN. In an embodiment, X 42ccr is --CN.

In an embodiment, Y 4ccr is selected from: S and NH. In an embodiment, Y 4ccr is S. I n an embodiment, R41ccr is selected from: C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro and chloro, and cycloalkyl. In an embodiment, R 41ccr is selected from ethyl, cyclopropyl and 2,2,2,trifluoroethyl. In an embodiment, R 41ccr is ethyl.

In an embodiment, R 43ccr is selected from: phenyl, phenyl subsitituted with 1 or 2 substituents independently selected form: -OS(O) 2 CH 3 , -N(CH 3 )S(O) 2 CH 3 , -CH 2 NHC(O)CH 3 , -CH 2 NHC(O)CH 2 NH 2 , -CH 2 NHC(O)CH 3 , tetrahydrothiazolyl, tetrehydrothiazolyl substituted once or twice by oxo, tetrahydrothiazinyl, tetrahydrothiazinyl substituted once or twice by oxo, and -CH 2 S(O) 2 CH 3 ,

In an embodiment R 44ccr and R 45ccr are independently selected from: hydrogen, methyl, and C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: -N(CH 2 CH 3 ) 2 , and -NHOC(CH 3 ) 2 NH 2 .

In an embodiment R 44ccr and R 45ccr are taken together with the nitrogen to which they are attached to form: piperidinyl, piperidinyl substituted by one or two substituents independently selected from: amino, -NHCH(CH 3 ), pyrrolidinyl, -NHC(O)C(CH 3 ) 3 , -NH(O)CH(CH 3 )(NH 2 ), fluoro, chloro, and CH 2 N(CH 3 ) 2 , morpholinyl, morpholinyl substituted by CH 2 pyrrolidinyl, 1,4diazepanyl, and methyl1,4diazepanyl. In an embodiment, X 41bbr is selected from: --CN, fluoro and chloro. In an embodiment, X 42bbr is selected from: --CN, fluoro and chloro. In an embodiment, X 41bbr is --CN. In an embodiment, X 42bbr is --CN.

In an embodiment, Y 4bbr is selected from: S and NH. In an embodiment, Y 4bbr is S.

I n an embodiment, R41bbr is selected from: C 1-6 alkyl, C 1-6 alkyl substituted with from 1 to 9 substituents independently selected from: fluoro and chloro, and cycloalkyl. In an embodiment, R 41bbr is selected from ethyl, cyclopropyl and 2,2,2,trifluoroethyl. In an embodiment, R 41bbr is ethyl.

In an embodiment, R 43bbr is selected from: phenyl, and phenyl subsitituted with 1 or 2 substituents independently selected form: fluoro and chloro.

In an embodiment R 44bbr and R 45bbr are independently selected from: methyl, and -CH 2 C(O)NH 2 .

In an embodiment R 44bbr and R 45bbr are taken together with the nitrogen to which they are attached to form: piperidinyl, piperidinyl substituted by one or two substituents independently selected from: amino, -NHCH 2 C(CH 3 ) 3 , flouro, chloro, and -N(CH 3 )cyclobutyl, pyrrolidinyl, and pyrrolidinyl substituted by hydroxy.

Included in the compounds of Formula (I) and in the methods of the invention are: 2-[(6-amino-3,5-dicyano-4-ethylpyridin-2-yl)sulfanyl]-2-phen ylacetamide;

(R)-[(6-amino-3,5-dicyano-4-ethylpyridin-2-yl)sulfanyl]-2-ph enylacetamide;

2-{[3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl]sulfan yl}-2-phenylacetamide; 2-((3,5-dicyano-4-cyclopropyl-6-(1,4-diazepan-1-yl)pyridin-2 -yl)thio)-2- phenylacetamide;

2-{[3,5-dicyano-4-cyclopropyl-6-(4-ethyl-1,4-diazepan-1-yl)p yridin-2-yl]sulfanyl}-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-propyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2- phenylacetamide;

2-{[3,5-dicyano-4-ethyl-6-(4-ethyl-1,4-diazepan-1-yl)pyridin -2-yl]sulfanyl}-2- phenylacetamide;

2-{[3,5-dicyano-4-ethyl-6-(5-oxo-1,4-diazepan-1-yl)pyridin-2 -yl]sulfanyl}-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-morpholinopyridin-2-yl)thio) -2-(pyridin-4- yl)acetamide;

2-{[3,5-dicyano-4-ethyl-6-(4-methyl-3-oxopiperazin-1-yl)pyri din-2-yl]sulfanyl}-2- (pyridin-4-yl)acetamide;

2-[(3,5-dicyano-4-ethyl-6-{methyl[2-(morpholin-4-yl)ethyl]am ino}pyridin-2- yl)sulfanyl]-2-phenylacetamide;

2-{[3,5-dicyano-4-ethyl-6-(4-propylpiperazin-1-yl)pyridin-2- yl]sulfanyl}-2- phenylacetamide;

2-({3,5-dicyano-4-ethyl-6-[4-(piperidin-4-yl)piperazin-1-yl] pyridin-2-yl}sulfanyl)-2- phenylacetamide;

2-({3,5-dicyano-4-cyclopropyl-6-[3-(hydroxymethyl)piperazin- 1-yl]pyridin-2- yl}sulfanyl)-2-phenylacetamide; 2-{[3,5-dicyano-4-cyclopropyl-6-(3-oxopiperazin-1-yl)pyridin -2-yl]sulfanyl}-2- phenylacetamide;

2-({3,5-dicyano-4-cyclopropyl-6-[4-(morpholin-4-yl)piperidin -1-yl]pyridin-2- yl}sulfanyl)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(2,8-diazaspiro[4.5]decan-8-yl)pyr idin-2-yl)thio)-2- phenylacetamide; 2,2,2-trifluoroacetic acid;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-(dimethylamino)piperidin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-methylpiperazin-1-yl)pyri din-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(2-(hydroxymethyl)morpholino )pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(2,6-dimethylmorpholino)pyri din-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-(dimethylamino)piperidin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((6-(4-(Aminomethyl)-4-hydroxypiperidin-1-yl)-3,5-dicyano- 4-cyclopropylpyridin- 2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(3-(methylamino)piperidin-1- yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(3-aminopiperidin-1-yl)-3,5-dicyano-4-cyclopropylpyrid in-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(dimethylamino)pyridin-2-yl) thio)-2-(pyridin-4- yl)acetamide;

2-((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-(pyridin-4- yl)acetamide;

2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-cyclopropylpyrid in-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(4-(dimethylamino)piperidin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide; 2-((3,5-dicyano-4-cyclopropyl-6-(piperazin-1-yl)pyridin-2-yl )thio)-2-(pyridin-4- yl)acetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(1,4-diazepan-1-yl)pyridin-2 -yl)thio)-2-(pyridin-4- yl)acetamide;

2-((3,5-dicyano-4-cyclopropyl-6-((R)-3-hydroxypiperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide;

2-(3,5-dicyano-4-cyclopropyl-6-((S)-3-hydroxypiperidin-1-yl) pyridin-2-ylthio)-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-((S)-3-hydroxypyrrolidin-1-y l)pyridin-2-yl)thio)-2- (pyridin-4-yl)acetamide;

2-((3,5-dicyano-4-ethyl-6-(4-ethylpiperazin-1-yl)pyridin-2-y l)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(1-oxa-6-azaspiro[3.4]octan-6-yl)p yridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-(3-aminopropyl)piperazin-1-yl)-3,5-dicyano-4-ethylp yridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(1,7-diazaspiro[3.5]nonan-1-yl)pyr idin-2-yl)thio)-2- phenylacetamide trifluoroacetate;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-(pyrrolidin-1-ylmethyl)pi peridin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-(4-methylpiperazin-1-yl)p iperidin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

(R)-2-((3,5-dicyano-6-(1,4-diazepan-1-yl)-4-ethylpyridin-2-y l)amino)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-(pyrrolidin-1-yl)piperidi n-1-yl)pyridin-2-yl)thio)- 2-phenylacetamide trifluoroacetate;

2-((3,5-Dicyano-4-ethyl-6-(2,7-diazaspiro[3.5]nonan-7-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2,6-diazaspiro[3.4]octan-6-yl)pyr idin-2-yl)thio)-2- phenylacetamide; 2-((3,5-dicyano-4-cyclopropyl-6-(1,4-diazepan-1-yl)pyridin-2 -yl)thio)propanamide; 2-((3,5-Dicyano-4-ethyl-6-(4-(2-oxoimidazolidin-1-yl)piperid in-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-hydroxypiperidin-1-yl)pyridin-2 -yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl)pyri din-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(3-oxopiperazin-1-yl)pyridin-2-yl) thio)-2- phenylacetamide;

2-[(6-amino-3,5-dicyano-4-cyclopropyl-2-pyridyl)sulfanyl]-2- phenyl-acetamide; 2-((3,5-Dicyano-4-ethyl-6-(methylamino)pyridin-2-yl)thio)-2- phenylacetamide; 2-((3,5-Dicyano-4-ethyl-6-((2-methoxyethyl)(methyl)amino)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(3-methoxyazetidin-1-yl)pyridin-2- yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(piperazin-1-yl)pyridin-2-yl)thio) -2-phenylacetamide; 2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-morpholinopyridin-2-yl)thio)-2-phe nylacetamide;

2-[[6-(azetidin-1-yl)-3,5-dicyano-4-ethyl-2-pyridyl]sulfanyl ]-2-phenyl-acetamide; 2-((3,5-dicyano-4-ethyl-6-(4-oxopiperidin-1-yl)pyridin-2-yl) thio)-2-phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-(1'-(2-hydroxyethyl)-[4,4'-bipiper idin]-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-((3S,5R)-3,5-dimethylpiperazin-1-yl)-4-eth ylpyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(8-azabicyclo[3.2.1]octan-3-yl(methyl)amino)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(2-(hydroxymethyl)morpholino )pyridin-2-yl)thio)-2- phenylacetamide; (R)-2-((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)th io)-2-phenylacetamide; (R)-2-[(3,5-Dicyano-4-ethyl-6-morpholino-2-pyridyl)sulfanyl] -2-phenyl-acetamide; N-(4-((3,5-Dicyano-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1 -yl)pyridin-2- ylthio)methyl)benzyl)acetamide trifluoroacetate;

2-{[3,5-dicyano-4-ethyl-6-(5-methyl-1,4-diazepan-1-yl)pyridi n-2-yl]sulfanyl}-2- phenylacetamide;

2-(4-(Aminomethyl)benzylthio)-4-ethyl-6-(4-(pyrrolidin-1- yl)piperidin-1-yl)pyridine- 3,5-dicarbonitrile;

tert-Butyl 4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2- yl)thio)methyl)benzylcarbamate;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2- yl)thio)methyl)benzamide;

2-((4-(Aminomethyl)benzyl)thio)-4-ethyl-6-(4-methyl-1,4-diaz epan-1-yl)pyridine- 3,5-dicarbonitrile, 2Hydrochloride;

2-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)phenyl)acetic acid;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2- yl)thio)methyl)benzoic acid;

2-(Dimethylamino)-4-ethyl-6-(((6-oxo-1,6-dihydropyridin-3-yl )methyl)thio)pyridine- 3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)thiazol-2-yl)acetamide;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2- yl)thio)methyl)benzenesulfonamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)acetamide;

tert-Butyl(2-((4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diaz epan-1-yl)pyridin-2- yl)thio)methyl)benzyl)amino)-2-oxoethyl)carbamate; N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)methanesulfonamide;

2-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan -1-yl)pyridin-2- yl)thio)methyl)benzyl)acetamide;

2-(4-Aminopiperidin-1-yl)-6-(benzylthio)-4-ethylpyridine-3, 5-dicarbonitrile; 4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2- yl)thio)methyl)benzyl acetate;

2-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)phenyl acetamide;

2-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)phenyl)-N-methylacetamide;

4-Ethyl-2-((4-(hydroxymethyl)benzyl)thio)-6-(4-methyl-1,4-di azepan-1-yl)pyridine- 3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)-2-hydroxyacetamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)propionamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)isobutyramide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)-3-methylbutanamide;

4-Ethyl-2-((4-(((2-hydroxyethyl)amino)methyl)benzyl)thio)-6- (4-methyl-1,4- diazepan-1-yl)pyridine-3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-6-(4-methyl-1,4-diazepan-1-yl)-4-(methyl amino)pyridin-2- yl)thio)methyl)benzyl)acetamide;

2-(((2-Acetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)methyl)thio )-6-(dimethylamino)-4- ethylpyridine-3,5-dicarbonitrile;

2-((4-Cyanobenzyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1-y l)pyridine-3,5- dicarbonitrile; 2-Amino-N-(1-(6-(benzylthio)-3,5-dicyano-4-ethylpyridin-2-yl )piperidin-4- yl)acetamide, Trifluoroacetic acid salt;

2-Amino-N-(1-(6-(benzylthio)-3,5-dicyano-4-ethylpyridin-2-yl )piperidin-4-yl)-2- methylpropanamide, Formic acid salt;

3-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan -1-yl)pyridin-2- yl)thio)methyl)benzyl)propanamide;

(S)-2-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diaz epan-1-yl)pyridin-2- yl)thio)methyl)benzyl)propanamide;

(R)-2-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diaz epan-1-yl)pyridin-2- yl)thio)methyl)benzyl)propanamide;

1-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)-3-ethylurea;

1-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)-3-phenylurea;

N-(4-(((3,5-Dicyano-6-(4-methyl-1,4-diazepan-1-yl)-4-(methyl thio)pyridin-2- yl)thio)methyl)benzyl)acetamide;

(E)-3-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2- yl)thio)methyl)phenyl)acrylic acid, Trifluoroacetic acid salt;

N-(4-(((3,5-Dicyano-4-ethyl-6-((2-hydroxyethyl)(methyl)amino )pyridin-2- yl)thio)methyl)benzyl)acetamide;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2-yl)thio)methyl)-N- methylbenzenesulfonamide;

N-(4-(((3,5-Dicyano-4-ethoxy-6-(4-methyl-1,4-diazepan-1-yl)p yridin-2- yl)thio)methyl)benzyl)acetamide;

2-({3,5-Dicyano-4-ethyl-6-[4-(2-methoxyethyl)-1,4-diazepan-1 -yl]pyridin-2- yl}sulfanyl)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(2-hydroxypropyl)-1,4-diazepan- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

Methyl 2-[4-(6-{[carbamoyl(phenyl)methyl]sulfanyl}-3,5-dicyano-4-et hylpyridin-2- yl)-1,4-diazepan-1-yl]acetate; 2-{[3,5-Dicyano-4-cyclopropyl-6-(4-methyl-5-oxo-1,4-diazepan -1-yl)pyridin-2- yl]sulfanyl}-2-phenylacetamide;

2-{[3,5-Dicyano-4-cyclopropyl-6-(5-oxo-1,4-diazepan-1-yl)pyr idin-2-yl]sulfanyl}-2- phenylacetamide;

2-{[3,5-Dicyano-4-ethyl-6-(4-methyl-5-oxo-1,4-diazepan-1-yl) pyridin-2-yl]sulfanyl}- 2-phenylacetamide;

2-{[3,5-Dicyano-6-(1,4-diazepan-1-yl)-4-ethylpyridin-2-yl]su lfanyl}-2- phenylacetamide;

2-({3,5-Dicyano-6-[4-(2-hydroxyethyl)-1,4-diazepan-1-yl]-4-( 2,2,2- trifluoroethyl)pyridin-2-yl}sulfanyl)-2-phenylacetamide;

(2R)-2-({3,5-Dicyano-4-ethyl-6-[4-(2-hydroxyethyl)-1,4-diaze pan-1-yl]pyridin-2- yl}amino)-2-phenylacetamide;

2-({6-[(3S)-3-Aminopyrrolidin-1-yl]-3,5-dicyano-4-cyclopropy lpyridin-2-yl}sulfanyl)- 2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2,9-diazaspiro[5.5]undecan-9-yl)p yridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(hexahydro-1H-pyrrolo[1,2-a][1,4]d iazepin-2(3H)- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2-methyl-2,9-diazaspiro[5.5]undec an-9-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-(2-(cyclopropylmethyl)-2,9-diazaspiro[5.5] undecan-9-yl)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide hydrochloride;

2-((3,5-Dicyano-6-(4-(3-(dimethylamino)propyl)piperazin-1-yl )-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(pyrrolidin-3-yl)piperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide; 2,2,2-trifluoroacetic acid;

2-((6-([4,4'-Bipiperidin]-1-yl)-3,5-dicyano-4-ethylpyridin-2 -yl)thio)-2- phenylacetamide; 2,2,2-trifluoroacetic acid;

2-((6-(4-(2-Aminoethyl)piperazin-1-yl)-3,5-dicyano-4-ethylpy ridin-2-yl)thio)-2- phenylacetamide; 2-((6-(4-(3-Aminopropyl)piperazin-1-yl)-3,5-dicyano-4-cyclop ropylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-((4-methylpiperazin-1-yl) methyl)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide trifluoroacetate;

2-((6-(4-Acetylpiperazin-1-yl)-3,5-dicyano-4-ethylpyridin-2- yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(dimethylamino)pyridin-2-yl) thio)-2- phenylacetamide;

2-(4-Chlorophenyl)-2-((3,5-dicyano-6-(dimethylamino)-4-ethyl pyridin-2- yl)thio)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(2-hydroxyethyl)piperazin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-[(3,5-Dicyano-4-cyclopropyl-6-morpholino-2-pyridyl)sulfany l]-2-phenyl- acetamide;

2-((6-(4-Benzoylpiperazin-1-yl)-3,5-dicyano-4-ethylpyridin-2 -yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((5S,6S)-6-hydroxy-1-(methylsulfon yl)-1,8- diazaspiro[4.5]decan-8-yl)pyridin-2-yl)thio)-2-phenylacetami de;

2-((3,5-Dicyano-6-(4,4-difluoropiperidin-1-yl)-4-ethylpyridi n-2-yl)thio)-2- phenylacetamide;

(R)-2-((3,5-Dicyano-4-ethyl-6-((R)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-amino-4-methylpiperidin-1-yl)-3,5-dicyano-4-ethy lpyridin-2-yl)thio)-2- phenylacetamide;

2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)acetamide 2,2,2-trifluoroacetate;

(2S)-2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5 -dicyano-4- ethylpyridin-2-yl)piperidin-4-yl)propanamide 2,2,2-trifluoroacetate; 2-((6-(4-(3-aminooxetane-3-carbonyl)piperazin-1-yl)-3,5-dicy ano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide formate;

4-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)tetrahydro-2H-pyran-4-carboxamide 2,2,2-trifluoroacetate;

2-((6-(4-(4-aminotetrahydro-2H-pyran-4-carbonyl)piperazin-1- yl)-3,5-dicyano-4- ethylpyridin-2-yl)thio)-2-phenylacetamide 2,2,2-trifluoroacetate;

2-((3,5-dicyano-6-(4-(2-hydroxyethyl)-1,4-diazepan-1-yl)-4-m ethoxypyridin-2- yl)thio)-2-phenylacetamide;

2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-y l)thio)-2- phenylacetamide;

2-((6-((2-aminoethyl)(methyl)amino)-3,5-dicyano-4-ethylpyrid in-2-yl)thio)-2- phenylacetamide 2,2,2-trifluoroacetate;

2-((6-((2-amino-2-oxoethyl)(methyl)amino)-3,5-dicyano-4-ethy lpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(3-hydroxyazetidin-1-yl)pyridin-2- yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-hydroxyethyl)(methyl)amino)pyr idin-2-yl)thio)-2- phenylacetamide;

2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)-2-methylpropanamide;

2-((6-(4-(2-aminoethoxy)piperidin-1-yl)-3,5-dicyano-4-ethylp yridin-2-yl)thio)-2- phenylacetamide 2,2,2-trifluoroacetate;

2-((3,5-dicyano-4-ethyl-6-(3-hydroxypyrrolidin-1-yl)pyridin- 2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(2-hydroxyethoxy)piperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide;

N-(4-(((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin -2- yl)thio)methyl)benzyl)acetamide 2,2,2-trifluoroacetate; and

2-((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-(piperidin-4- yl)acetamide; or a pharmaceutically acceptable salt or prodrug thereof. Included prodrugs of Formula (I) of the invention are: 1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)pyrrolidin- 3-yl dihydrogen phosphate;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)ethyl dihydrogen phosphate;

1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)azetidin- 3-yl dihydrogen phosphate;

(2S)-2-((1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyan o-4-ethylpyridin-2- yl)piperidin-4-yl)oxy)ethyl 2-amino-3-methylbutanoate;

2-((1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-e thylpyridin-2- yl)piperidin-4-yl)oxy)ethyl dihydrogen phosphate;

1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)piperidin- 4-yl dihydrogen phosphate; or a pharmaceutically acceptable salt thereof. Suitably, the presently invented novel compounds of Formula (IVa) are selected from: 2-{[3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl]sulfan yl}-2-phenylacetamide; 2-((3,5-dicyano-4-cyclopropyl-6-(1,4-diazepan-1-yl)pyridin-2 -yl)thio)-2- phenylacetamide;

2-{[3,5-dicyano-4-cyclopropyl-6-(4-ethyl-1,4-diazepan-1-yl)p yridin-2-yl]sulfanyl}-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-propyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2- phenylacetamide;

2-{[3,5-dicyano-4-ethyl-6-(4-ethyl-1,4-diazepan-1-yl)pyridin -2-yl]sulfanyl}-2- phenylacetamide; 2-{[3,5-dicyano-4-ethyl-6-(5-oxo-1,4-diazepan-1-yl)pyridin-2 -yl]sulfanyl}-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-morpholinopyridin-2-yl)thio) -2-(pyridin-4- yl)acetamide;

2-{[3,5-dicyano-4-ethyl-6-(4-methyl-3-oxopiperazin-1-yl)pyri din-2-yl]sulfanyl}-2- (pyridin-4-yl)acetamide;

2-[(3,5-dicyano-4-ethyl-6-{methyl[2-(morpholin-4-yl)ethyl]am ino}pyridin-2- yl)sulfanyl]-2-phenylacetamide;

2-{[3,5-dicyano-4-ethyl-6-(4-propylpiperazin-1-yl)pyridin-2- yl]sulfanyl}-2- phenylacetamide;

2-({3,5-dicyano-4-ethyl-6-[4-(piperidin-4-yl)piperazin-1-yl] pyridin-2-yl}sulfanyl)-2- phenylacetamide;

2-({3,5-dicyano-4-cyclopropyl-6-[3-(hydroxymethyl)piperazin- 1-yl]pyridin-2- yl}sulfanyl)-2-phenylacetamide;

2-{[3,5-dicyano-4-cyclopropyl-6-(3-oxopiperazin-1-yl)pyridin -2-yl]sulfanyl}-2- phenylacetamide;

2-({3,5-dicyano-4-cyclopropyl-6-[4-(morpholin-4-yl)piperidin -1-yl]pyridin-2- yl}sulfanyl)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(2,8-diazaspiro[4.5]decan-8-yl)pyr idin-2-yl)thio)-2- phenylacetamide; 2,2,2-trifluoroacetic acid;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-(dimethylamino)piperidin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-methylpiperazin-1-yl)pyri din-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(2-(hydroxymethyl)morpholino )pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(2,6-dimethylmorpholino)pyri din-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-(dimethylamino)piperidin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide; 2-((6-(4-(Aminomethyl)-4-hydroxypiperidin-1-yl)-3,5-dicyano- 4-cyclopropylpyridin- 2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(3-(methylamino)piperidin-1- yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(3-aminopiperidin-1-yl)-3,5-dicyano-4-cyclopropylpyrid in-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(dimethylamino)pyridin-2-yl) thio)-2-(pyridin-4- yl)acetamide;

2-((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-(pyridin-4- yl)acetamide;

2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-cyclopropylpyrid in-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(4-(dimethylamino)piperidin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(piperazin-1-yl)pyridin-2-yl )thio)-2-(pyridin-4- yl)acetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(1,4-diazepan-1-yl)pyridin-2 -yl)thio)-2-(pyridin-4- yl)acetamide;

2-((3,5-dicyano-4-cyclopropyl-6-((R)-3-hydroxypiperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide;

2-(3,5-dicyano-4-cyclopropyl-6-((S)-3-hydroxypiperidin-1-yl) pyridin-2-ylthio)-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-((S)-3-hydroxypyrrolidin-1-y l)pyridin-2-yl)thio)-2- (pyridin-4-yl)acetamide;

2-((3,5-dicyano-4-ethyl-6-(4-ethylpiperazin-1-yl)pyridin-2-y l)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(1-oxa-6-azaspiro[3.4]octan-6-yl)p yridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-(3-aminopropyl)piperazin-1-yl)-3,5-dicyano-4-ethylp yridin-2-yl)thio)-2- phenylacetamide; 2-((3,5-Dicyano-4-ethyl-6-(1,7-diazaspiro[3.5]nonan-1-yl)pyr idin-2-yl)thio)-2- phenylacetamide trifluoroacetate;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-(pyrrolidin-1-ylmethyl)pi peridin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-(4-methylpiperazin-1-yl)p iperidin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

(R)-2-((3,5-dicyano-6-(1,4-diazepan-1-yl)-4-ethylpyridin-2-y l)amino)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-(pyrrolidin-1-yl)piperidi n-1-yl)pyridin-2-yl)thio)- 2-phenylacetamide trifluoroacetate;

2-((3,5-Dicyano-4-ethyl-6-(2,7-diazaspiro[3.5]nonan-7-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2,6-diazaspiro[3.4]octan-6-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(1,4-diazepan-1-yl)pyridin-2 -yl)thio)propanamide; 2-((3,5-Dicyano-4-ethyl-6-(4-(2-oxoimidazolidin-1-yl)piperid in-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-hydroxypiperidin-1-yl)pyridin-2 -yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl)pyri din-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(3-oxopiperazin-1-yl)pyridin-2-yl) thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((2-methoxyethyl)(methyl)amino)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(3-methoxyazetidin-1-yl)pyridin-2- yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(piperazin-1-yl)pyridin-2-yl)thio) -2-phenylacetamide; 2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2- phenylacetamide; 2-((3,5-Dicyano-4-ethyl-6-morpholinopyridin-2-yl)thio)-2-phe nylacetamide;

2-[[6-(azetidin-1-yl)-3,5-dicyano-4-ethyl-2-pyridyl]sulfanyl ]-2-phenyl-acetamide; 2-((3,5-dicyano-4-ethyl-6-(4-oxopiperidin-1-yl)pyridin-2-yl) thio)-2-phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-(1'-(2-hydroxyethyl)-[4,4'-bipiper idin]-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-((3S,5R)-3,5-dimethylpiperazin-1-yl)-4-eth ylpyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(8-azabicyclo[3.2.1]octan-3-yl(methyl)amino)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(2-(hydroxymethyl)morpholino )pyridin-2-yl)thio)-2- phenylacetamide;

(R)-2-((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)th io)-2-phenylacetamide; (R)-2-[(3,5-Dicyano-4-ethyl-6-morpholino-2-pyridyl)sulfanyl] -2-phenyl-acetamide; N-(4-((3,5-Dicyano-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1 -yl)pyridin-2- ylthio)methyl)benzyl)acetamide trifluoroacetate;

2-{[3,5-dicyano-4-ethyl-6-(5-methyl-1,4-diazepan-1-yl)pyridi n-2-yl]sulfanyl}-2- phenylacetamide;

2-(4-(Aminomethyl)benzylthio)-4-ethyl-6-(4-(pyrrolidin-1-yl) piperidin-1-yl)pyridine- 3,5-dicarbonitrile;

tert-Butyl 4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2- yl)thio)methyl)benzylcarbamate;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2- yl)thio)methyl)benzamide;

2-((4-(Aminomethyl)benzyl)thio)-4-ethyl-6-(4-methyl-1,4-diaz epan-1-yl)pyridine- 3,5-dicarbonitrile, 2Hydrochloride;

2-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)phenyl)acetic acid;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2- yl)thio)methyl)benzoic acid; 2-(Dimethylamino)-4-ethyl-6-(((6-oxo-1,6-dihydropyridin-3-yl )methyl)thio)pyridine- 3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)thiazol-2-yl)acetamide;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2- yl)thio)methyl)benzenesulfonamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)acetamide;

tert-Butyl(2-((4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diaz epan-1-yl)pyridin-2- yl)thio)methyl)benzyl)amino)-2-oxoethyl)carbamate;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)methanesulfonamide;

2-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan -1-yl)pyridin-2- yl)thio)methyl)benzyl)acetamide;

2-(4-Aminopiperidin-1-yl)-6-(benzylthio)-4-ethylpyridine-3, 5-dicarbonitrile; 4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2- yl)thio)methyl)benzyl acetate;

2-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)phenyl acetamide;

2-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)phenyl)-N-methylacetamide;

4-Ethyl-2-((4-(hydroxymethyl)benzyl)thio)-6-(4-methyl-1,4-di azepan-1-yl)pyridine- 3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)-2-hydroxyacetamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)propionamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)isobutyramide; N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)-3-methylbutanamide;

4-Ethyl-2-((4-(((2-hydroxyethyl)amino)methyl)benzyl)thio)-6- (4-methyl-1,4- diazepan-1-yl)pyridine-3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-6-(4-methyl-1,4-diazepan-1-yl)-4-(methyl amino)pyridin-2- yl)thio)methyl)benzyl)acetamide;

2-(((2-Acetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)methyl)thio )-6-(dimethylamino)-4- ethylpyridine-3,5-dicarbonitrile;

2-((4-Cyanobenzyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1-y l)pyridine-3,5- dicarbonitrile;

2-Amino-N-(1-(6-(benzylthio)-3,5-dicyano-4-ethylpyridin-2-yl )piperidin-4- yl)acetamide, Trifluoroacetic acid salt;

2-Amino-N-(1-(6-(benzylthio)-3,5-dicyano-4-ethylpyridin-2-yl )piperidin-4-yl)-2- methylpropanamide, Formic acid salt;

3-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan -1-yl)pyridin-2- yl)thio)methyl)benzyl)propanamide;

(S)-2-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diaz epan-1-yl)pyridin-2- yl)thio)methyl)benzyl)propanamide;

(R)-2-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diaz epan-1-yl)pyridin-2- yl)thio)methyl)benzyl)propanamide;

1-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)-3-ethylurea;

1-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)-3-phenylurea;

N-(4-(((3,5-Dicyano-6-(4-methyl-1,4-diazepan-1-yl)-4-(methyl thio)pyridin-2- yl)thio)methyl)benzyl)acetamide;

(E)-3-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2- yl)thio)methyl)phenyl)acrylic acid, Trifluoroacetic acid salt;

N-(4-(((3,5-Dicyano-4-ethyl-6-((2-hydroxyethyl)(methyl)amino )pyridin-2- yl)thio)methyl)benzyl)acetamide; 4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2-yl)thio)methyl)-N- methylbenzenesulfonamide;

N-(4-(((3,5-Dicyano-4-ethoxy-6-(4-methyl-1,4-diazepan-1-yl)p yridin-2- yl)thio)methyl)benzyl)acetamide;

2-({3,5-Dicyano-4-ethyl-6-[4-(2-methoxyethyl)-1,4-diazepa n-1-yl]pyridin-2- yl}sulfanyl)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(2-hydroxypropyl)-1,4-diazepan- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

Methyl 2-[4-(6-{[carbamoyl(phenyl)methyl]sulfanyl}-3,5-dicyano-4-et hylpyridin-2- yl)-1,4-diazepan-1-yl]acetate;

2-{[3,5-Dicyano-4-cyclopropyl-6-(4-methyl-5-oxo-1,4-diazepan -1-yl)pyridin-2- yl]sulfanyl}-2-phenylacetamide;

2-{[3,5-Dicyano-4-cyclopropyl-6-(5-oxo-1,4-diazepan-1-yl)pyr idin-2-yl]sulfanyl}-2- phenylacetamide;

2-{[3,5-Dicyano-4-ethyl-6-(4-methyl-5-oxo-1,4-diazepan-1-yl) pyridin-2-yl]sulfanyl}- 2-phenylacetamide;

2-{[3,5-Dicyano-6-(1,4-diazepan-1-yl)-4-ethylpyridin-2-yl]su lfanyl}-2- phenylacetamide;

2-({3,5-Dicyano-6-[4-(2-hydroxyethyl)-1,4-diazepan-1-yl]-4-( 2,2,2- trifluoroethyl)pyridin-2-yl}sulfanyl)-2-phenylacetamide;

(2R)-2-({3,5-Dicyano-4-ethyl-6-[4-(2-hydroxyethyl)-1,4-diaze pan-1-yl]pyridin-2- yl}amino)-2-phenylacetamide;

2-({6-[(3S)-3-Aminopyrrolidin-1-yl]-3,5-dicyano-4-cyclopropy lpyridin-2-yl}sulfanyl)- 2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2,9-diazaspiro[5.5]undecan-9-yl)p yridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(hexahydro-1H-pyrrolo[1,2-a][1,4]d iazepin-2(3H)- yl)pyridin-2-yl)thio)-2-phenylacetamide; 2-((3,5-Dicyano-4-ethyl-6-(2-methyl-2,9-diazaspiro[5.5]undec an-9-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-(2-(cyclopropylmethyl)-2,9-diazaspiro[5.5] undecan-9-yl)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide hydrochloride;

2-((3,5-Dicyano-6-(4-(3-(dimethylamino)propyl)piperazin-1-yl )-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(pyrrolidin-3-yl)piperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide; 2,2,2-trifluoroacetic acid;

2-((6-([4,4'-Bipiperidin]-1-yl)-3,5-dicyano-4-ethylpyridin-2 -yl)thio)-2- phenylacetamide; 2,2,2-trifluoroacetic acid;

2-((6-(4-(2-Aminoethyl)piperazin-1-yl)-3,5-dicyano-4-ethylpy ridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-(3-Aminopropyl)piperazin-1-yl)-3,5-dicyano-4-cyclop ropylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-((4-methylpiperazin-1-yl) methyl)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide trifluoroacetate;

2-((6-(4-Acetylpiperazin-1-yl)-3,5-dicyano-4-ethylpyridin-2- yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(dimethylamino)pyridin-2-yl) thio)-2- phenylacetamide;

2-(4-Chlorophenyl)-2-((3,5-dicyano-6-(dimethylamino)-4-ethyl pyridin-2- yl)thio)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(2-hydroxyethyl)piperazin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-[(3,5-Dicyano-4-cyclopropyl-6-morpholino-2-pyridyl)sulfany l]-2-phenyl- acetamide;

2-((6-(4-Benzoylpiperazin-1-yl)-3,5-dicyano-4-ethylpyridin-2 -yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((5S,6S)-6-hydroxy-1-(methylsulfon yl)-1,8- diazaspiro[4.5]decan-8-yl)pyridin-2-yl)thio)-2-phenylacetami de; 2-((3,5-Dicyano-6-(4,4-difluoropiperidin-1-yl)-4-ethylpyridi n-2-yl)thio)-2- phenylacetamide;

(R)-2-((3,5-Dicyano-4-ethyl-6-((R)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-amino-4-methylpiperidin-1-yl)-3,5-dicyano-4-ethy lpyridin-2-yl)thio)-2- phenylacetamide;

2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)acetamide 2,2,2-trifluoroacetate;

(2S)-2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5 -dicyano-4- ethylpyridin-2-yl)piperidin-4-yl)propanamide 2,2,2-trifluoroacetate;

2-((6-(4-(3-aminooxetane-3-carbonyl)piperazin-1-yl)-3,5-dicy ano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide formate;

4-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)tetrahydro-2H-pyran-4-carboxamide 2,2,2-trifluoroacetate;

2-((6-(4-(4-aminotetrahydro-2H-pyran-4-carbonyl)piperazin-1- yl)-3,5-dicyano-4- ethylpyridin-2-yl)thio)-2-phenylacetamide 2,2,2-trifluoroacetate;

2-((3,5-dicyano-6-(4-(2-hydroxyethyl)-1,4-diazepan-1-yl)-4-m ethoxypyridin-2- yl)thio)-2-phenylacetamide;

2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-y l)thio)-2- phenylacetamide;

2-((6-((2-aminoethyl)(methyl)amino)-3,5-dicyano-4-ethylpyrid in-2-yl)thio)-2- phenylacetamide 2,2,2-trifluoroacetate;

2-((6-((2-amino-2-oxoethyl)(methyl)amino)-3,5-dicyano-4-ethy lpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(3-hydroxyazetidin-1-yl)pyridin-2- yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-hydroxyethyl)(methyl)amino)pyr idin-2-yl)thio)-2- phenylacetamide; 2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)-2-methylpropanamide;

2-((6-(4-(2-aminoethoxy)piperidin-1-yl)-3,5-dicyano-4-ethylp yridin-2-yl)thio)-2- phenylacetamide 2,2,2-trifluoroacetate;

2-((3,5-dicyano-4-ethyl-6-(3-hydroxypyrrolidin-1-yl)pyridin- 2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(2-hydroxyethoxy)piperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide;

N-(4-(((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin -2- yl)thio)methyl)benzyl)acetamide 2,2,2-trifluoroacetate; and

2-((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-(piperidin-4- yl)acetamide;

or a pharmaceutically acceptable salt or prodrug thereof. Included prodrugs of Formula (IVa) of the invention are: 1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)pyrrolidin- 3-yl dihydrogen phosphate;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)ethyl dihydrogen phosphate;

1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)azetidin- 3-yl dihydrogen phosphate;

(2S)-2-((1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyan o-4-ethylpyridin-2- yl)piperidin-4-yl)oxy)ethyl 2-amino-3-methylbutanoate;

2-((1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-e thylpyridin-2- yl)piperidin-4-yl)oxy)ethyl dihydrogen phosphate;

1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)piperidin- 4-yl dihydrogen phosphate; or a pharmaceutically acceptable salt thereof. Primary amide:

Included in the compounds of Formula (Ibr) and in the methods of the invention are: 2-[(6-amino-3,5-dicyano-4-ethylpyridin-2-yl)sulfanyl]-2-phen ylacetamide;

(R)-[(6-amino-3,5-dicyano-4-ethylpyridin-2-yl)sulfanyl]-2-ph enylacetamide;

2-{[3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl]sulfan yl}-2-phenylacetamide; 2-((3,5-dicyano-4-cyclopropyl-6-(1,4-diazepan-1-yl)pyridin-2 -yl)thio)-2- phenylacetamide;

2-{[3,5-dicyano-4-cyclopropyl-6-(4-ethyl-1,4-diazepan-1-yl)p yridin-2-yl]sulfanyl}-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-propyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2- phenylacetamide;

2-{[3,5-dicyano-4-ethyl-6-(4-ethyl-1,4-diazepan-1-yl)pyridin -2-yl]sulfanyl}-2- phenylacetamide;

2-{[3,5-dicyano-4-ethyl-6-(5-oxo-1,4-diazepan-1-yl)pyridin-2 -yl]sulfanyl}-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-morpholinopyridin-2-yl)thio) -2-(pyridin-4- yl)acetamide;

2-{[3,5-dicyano-4-ethyl-6-(4-methyl-3-oxopiperazin-1-yl)pyri din-2-yl]sulfanyl}-2- (pyridin-4-yl)acetamide;

2-[(3,5-dicyano-4-ethyl-6-{methyl[2-(morpholin-4-yl)ethyl]am ino}pyridin-2- yl)sulfanyl]-2-phenylacetamide;

2-{[3,5-dicyano-4-ethyl-6-(4-propylpiperazin-1-yl)pyridin-2- yl]sulfanyl}-2- phenylacetamide;

2-({3,5-dicyano-4-ethyl-6-[4-(piperidin-4-yl)piperazin-1-yl] pyridin-2-yl}sulfanyl)-2- phenylacetamide;

2-({3,5-dicyano-4-cyclopropyl-6-[3-(hydroxymethyl)piperazin- 1-yl]pyridin-2- yl}sulfanyl)-2-phenylacetamide;

2-{[3,5-dicyano-4-cyclopropyl-6-(3-oxopiperazin-1-yl)pyridin -2-yl]sulfanyl}-2- phenylacetamide; 2-({3,5-dicyano-4-cyclopropyl-6-[4-(morpholin-4-yl)piperidin -1-yl]pyridin-2- yl}sulfanyl)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(2,8-diazaspiro[4.5]decan-8-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-(dimethylamino)piperidin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-methylpiperazin-1-yl)pyri din-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(2-(hydroxymethyl)morpholino )pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(2,6-dimethylmorpholino)pyri din-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-(dimethylamino)piperidin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((6-(4-(Aminomethyl)-4-hydroxypiperidin-1-yl)-3,5-dicyano- 4-cyclopropylpyridin- 2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(3-(methylamino)piperidin-1- yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(3-aminopiperidin-1-yl)-3,5-dicyano-4-cyclopropylpyrid in-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(dimethylamino)pyridin-2-yl) thio)-2-(pyridin-4- yl)acetamide;

2-((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-(pyridin-4- yl)acetamide;

2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-cyclopropylpyrid in-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(4-(dimethylamino)piperidin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(piperazin-1-yl)pyridin-2-yl )thio)-2-(pyridin-4- yl)acetamide; 2-((3,5-dicyano-4-cyclopropyl-6-(1,4-diazepan-1-yl)pyridin-2 -yl)thio)-2-(pyridin-4- yl)acetamide;

2-((3,5-dicyano-4-cyclopropyl-6-((R)-3-hydroxypiperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide;

2-(3,5-dicyano-4-cyclopropyl-6-((S)-3-hydroxypiperidin-1-yl) pyridin-2-ylthio)-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-((S)-3-hydroxypyrrolidin-1-y l)pyridin-2-yl)thio)-2- (pyridin-4-yl)acetamide;

2-((3,5-dicyano-4-ethyl-6-(4-ethylpiperazin-1-yl)pyridin-2-y l)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(1-oxa-6-azaspiro[3.4]octan-6-yl)p yridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-(3-aminopropyl)piperazin-1-yl)-3,5-dicyano-4-ethylp yridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(1,7-diazaspiro[3.5]nonan-1-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-(pyrrolidin-1-ylmethyl)pi peridin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-(4-methylpiperazin-1-yl)p iperidin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

(R)-2-((3,5-dicyano-6-(1,4-diazepan-1-yl)-4-ethylpyridin-2-y l)amino)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-(pyrrolidin-1-yl)piperidi n-1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2,7-diazaspiro[3.5]nonan-7-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2,6-diazaspiro[3.4]octan-6-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(1,4-diazepan-1-yl)pyridin-2 -yl)thio)propanamide; 2-((3,5-Dicyano-4-ethyl-6-(4-(2-oxoimidazolidin-1-yl)piperid in-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-hydroxypiperidin-1-yl)pyridin-2 -yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl)pyri din-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(3-oxopiperazin-1-yl)pyridin-2-yl) thio)-2- phenylacetamide;

2-[(6-amino-3,5-dicyano-4-cyclopropyl-2-pyridyl)sulfanyl]-2- phenyl-acetamide; 2-((3,5-Dicyano-4-ethyl-6-(methylamino)pyridin-2-yl)thio)-2- phenylacetamide; 2-((3,5-Dicyano-4-ethyl-6-((2-methoxyethyl)(methyl)amino)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(3-methoxyazetidin-1-yl)pyridin-2- yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(piperazin-1-yl)pyridin-2-yl)thio) -2-phenylacetamide; 2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-morpholinopyridin-2-yl)thio)-2-phe nylacetamide;

2-[[6-(azetidin-1-yl)-3,5-dicyano-4-ethyl-2-pyridyl]sulfanyl ]-2-phenyl-acetamide; 2-((3,5-dicyano-4-ethyl-6-(4-oxopiperidin-1-yl)pyridin-2-yl) thio)-2-phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-(1'-(2-hydroxyethyl)-[4,4'-bipiper idin]-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-((3S,5R)-3,5-dimethylpiperazin-1-yl)-4-eth ylpyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(8-azabicyclo[3.2.1]octan-3-yl(methyl)amino)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(2-(hydroxymethyl)morpholino )pyridin-2-yl)thio)-2- phenylacetamide;

(R)-2-((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)th io)-2-phenylacetamide; (R)-2-[(3,5-Dicyano-4-ethyl-6-morpholino-2-pyridyl)sulfanyl] -2-phenyl-acetamide; 2-{[3,5-dicyano-4-ethyl-6-(5-methyl-1,4-diazepan-1-yl)pyridi n-2-yl]sulfanyl}-2- phenylacetamide;

2-({3,5-Dicyano-4-ethyl-6-[4-(2-methoxyethyl)-1,4-diazepan-1 -yl]pyridin-2- yl}sulfanyl)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(2-hydroxypropyl)-1,4-diazepan- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

Methyl 2-[4-(6-{[carbamoyl(phenyl)methyl]sulfanyl}-3,5-dicyano-4-et hylpyridin-2- yl)-1,4-diazepan-1-yl]acetate;

2-{[3,5-Dicyano-4-cyclopropyl-6-(4-methyl-5-oxo-1,4-diazepan -1-yl)pyridin-2- yl]sulfanyl}-2-phenylacetamide;

2-{[3,5-Dicyano-4-cyclopropyl-6-(5-oxo-1,4-diazepan-1-yl)pyr idin-2-yl]sulfanyl}-2- phenylacetamide;

2-{[3,5-Dicyano-4-ethyl-6-(4-methyl-5-oxo-1,4-diazepan-1-yl) pyridin-2-yl]sulfanyl}- 2-phenylacetamide;

2-{[3,5-Dicyano-6-(1,4-diazepan-1-yl)-4-ethylpyridin-2-yl]su lfanyl}-2- phenylacetamide;

2-({3,5-Dicyano-6-[4-(2-hydroxyethyl)-1,4-diazepan-1-yl]-4-( 2,2,2- trifluoroethyl)pyridin-2-yl}sulfanyl)-2-phenylacetamide;

(2R)-2-({3,5-Dicyano-4-ethyl-6-[4-(2-hydroxyethyl)-1,4-diaze pan-1-yl]pyridin-2- yl}amino)-2-phenylacetamide;

2-({6-[(3S)-3-Aminopyrrolidin-1-yl]-3,5-dicyano-4-cyclopropy lpyridin-2-yl}sulfanyl)- 2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2,9-diazaspiro[5.5]undecan-9-yl)p yridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(hexahydro-1H-pyrrolo[1,2-a][1,4]d iazepin-2(3H)- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2-methyl-2,9-diazaspiro[5.5]undec an-9-yl)pyridin-2- yl)thio)-2-phenylacetamide; 2-((3,5-Dicyano-6-(2-(cyclopropylmethyl)-2,9-diazaspiro[5.5] undecan-9-yl)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-(4-(3-(dimethylamino)propyl)piperazin-1-yl )-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(pyrrolidin-3-yl)piperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-([4,4'-Bipiperidin]-1-yl)-3,5-dicyano-4-ethylpyridin-2 -yl)thio)-2- phenylacetamide;

2-((6-(4-(2-Aminoethyl)piperazin-1-yl)-3,5-dicyano-4-ethylpy ridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-(3-Aminopropyl)piperazin-1-yl)-3,5-dicyano-4-cyclop ropylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-((4-methylpiperazin-1-yl) methyl)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((6-(4-Acetylpiperazin-1-yl)-3,5-dicyano-4-ethylpyridin-2- yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(dimethylamino)pyridin-2-yl) thio)-2- phenylacetamide;

2-(4-Chlorophenyl)-2-((3,5-dicyano-6-(dimethylamino)-4-ethyl pyridin-2- yl)thio)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(2-hydroxyethyl)piperazin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-[(3,5-Dicyano-4-cyclopropyl-6-morpholino-2-pyridyl)sulfany l]-2-phenyl- acetamide;

2-((6-(4-Benzoylpiperazin-1-yl)-3,5-dicyano-4-ethylpyridin-2 -yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((5S,6S)-6-hydroxy-1-(methylsulfon yl)-1,8- diazaspiro[4.5]decan-8-yl)pyridin-2-yl)thio)-2-phenylacetami de;

2-((3,5-Dicyano-6-(4,4-difluoropiperidin-1-yl)-4-ethylpyridi n-2-yl)thio)-2- phenylacetamide; (R)-2-((3,5-Dicyano-4-ethyl-6-((R)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-(furan-2-yl)-6-(4-methyl-1,4-diazepan-1-yl )pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-Amino-4-methylpiperidin-1-yl)-3,5-dicyano-4-ethylpy ridin-2-yl)thio)-2- phenylacetamide;

2-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)acetamide;

(2S)-2-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5 -dicyano-4- ethylpyridin-2-yl)piperidin-4-yl)propanamide;

2-((6-(4-(3-Aminooxetane-3-carbonyl)piperazin-1-yl)-3,5-dicy ano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

4-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)tetrahydro-2H-pyran-4-carboxamide;

2-((6-(4-(4-Aminotetrahydro-2H-pyran-4-carbonyl)piperazin-1- yl)-3,5-dicyano-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-(4-(2-hydroxyethyl)-1,4-diazepan-1-yl)-4-m ethoxypyridin-2- yl)thio)-2-phenylacetamide;

2-((6-(4-Aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-y l)thio)-2- phenylacetamide;

2-((6-((2-Aminoethyl)(methyl)amino)-3,5-dicyano-4-ethylpyrid in-2-yl)thio)-2- phenylacetamide;

2-((6-((2-Amino-2-oxoethyl)(methyl)amino)-3,5-dicyano-4-ethy lpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(3-hydroxyazetidin-1-yl)pyridin-2- yl)thio)-2- phenylacetamide;

2-(3,5-Dicyano-4-ethyl-6-((2-hydroxyethyl)(methyl)amino)pyri din-2-ylthio)-2- phenylacetamide;

2-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)-2-methylpropanamide; 2-((6-(4-(2-Aminoethoxy)piperidin-1-yl)-3,5-dicyano-4-ethylp yridin-2-yl)thio)-2- phenylacetamide;

1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)pyrrolidin- 3-yl dihydrogen phosphate;

2-((6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)ethyl dihydrogen phosphate;

1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)azetidin- 3-yl dihydrogen phosphate;

(2S)-2-((1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyan o-4-ethylpyridin-2- yl)piperidin-4-yl)oxy)ethyl 2-amino-3-methylbutanoate;

2-((1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-e thylpyridin-2- yl)piperidin-4-yl)oxy)ethyl dihydrogen phosphate;

1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)piperidin- 4-yl dihydrogen phosphate;

2-((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-(piperidin-4- yl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(propylsulfonyl)piperazin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(phenylsulfonyl)piperazin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((R)-3-hydroxypyrrolidin-1-yl)pyri din-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2-oxa-6-azaspiro[3.4]octan-6-yl)p yridin-2-yl)thio)-2- phenylacetamide;

(R)-2-((3,5-Dicyano-4-ethyl-6-(4-ethyl-1,4-diazepan-1-yl)pyr idin-2-yl)amino)-2- phenylacetamide;

(R)-2-((3,5-Dicyano-4-ethyl-6-(4-(3-(pyrrolidin-1-yl)propyl) -1,4-diazepan-1- yl)pyridin-2-yl)amino)-2-phenylacetamide;

2-(3,5-Dicyano-4-cyclopropyl-6-(3-hydroxypiperidin-1-yl)pyri din-2-ylthio)-2- phenylacetamide; 2-((3,5-Dichloro-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-6-(1,1-dioxidothiomorpholino)-4-ethylpyridin -2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(methyl(2-(piperazin-1-yl)ethyl)am ino)pyridin-2-yl)thio)- 2-phenylacetamide;

(R)-2-((3,5-Dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-((2-(4-(Aminomethyl)-4-hydroxypiperidin-1-yl)ethyl)(me thyl)amino)-3,5- dicyano-4-ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((4-Cyano-3-(1,4-diazepan-1-yl)-6,7-dihydro-5H-cyclopenta[ c]pyridin-1-yl)thio)-2- phenylacetamide;

2-((6-(4-(1H-Imidazol-1-yl)piperidin-1-yl)-3,5-dicyano-4-eth ylpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(pyridin-4-ylmethyl)piperazin-1 -yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-6-(2-(dimethylamino)ethoxy)-4-ethylpyridin-2 -yl)thio)-2- phenylacetamide;

2-((1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-c yclopropylpyridin-2- yl)piperidin-3-yl)amino)acetic acid;

2-((3,5-Dicyano-4-ethyl-6-(4-(oxazol-2-ylmethyl)piperazin-1- yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-((1H-Pyrrol-2-yl) methyl) piperazin-1-yl)-3,5-dicyano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-(3,4-dihydro-2,7-naphthyridin-2 (1H)-yl)-4-ethylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl)pyri din-2-yl)thio)-2-(pyridin- 3-yl)acetamide;

2-((6-(4-((1H-Pyrrol-3-yl)methyl)piperazin-1-yl)-3,5-dicyano -4-ethylpyridin-2- yl)thio)-2-phenylacetamide; 2-((3,5-Dicyano-4-ethyl-6-(4-(isoxazol-3-ylmethyl)piperazin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(oxazol-5-ylmethyl)piperazin-1- yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(isoxazol-4-ylmethyl)piperazin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

3-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)oxetane-3-carboxamide;

2-((6-(4-((1H-Pyrazol-4-yl)methyl)piperazin-1-yl)-3,5-dicyan o-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-(4-((1H-Imidazol-5-yl)methyl)piperazin-1-yl)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(1-hydroxy-2-methylpropan-2-yl) piperazin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((6-(4-((1H-Imidazol-2-yl)methyl)piperazin-1-yl)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-(dimethylamino)-4-methoxypyridin-2-yl)thio )-2-phenylacetamide; 2-((3,5-Dicyano-6-(dimethylamino)-4-ethoxypyridin-2-yl)thio) -2-phenylacetamide; 2-((3,5-Dicyano-4-ethoxy-6-(4-(2-hydroxyethyl)-1,4-diazepan- 1-yl) pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(2-hydroxy-2-methylpropyl)-1,4- diazepan-1-yl)pyridin- 2-yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(thiazol-5-ylmethyl)piperazin-1 -yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(piperazin-1-yl)pyridin-2-yl)thio) -2-(4- fluorophenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(isothiazol-4-ylmethyl)piperazi n-1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-(4- fluorophenyl)acetamide; 2-((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2- (5-fluoropyridin-2- yl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(furan-3-ylmethyl)piperazin-1-y l)pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((2-morpholinoethyl)thio)pyridin-2 -yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-6-(4-methyl-1,4-diazepan-1-yl)-4-(methylthio )pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dichloro-4-ethyl-6-(4-(2-hydroxyethyl)-1,4-diazepan- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(hexahydropyrrolo[3,4-b][1,4]oxazi n-6(2H)-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(5- methylpyridin-2-yl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(6- fluoropyridin-2-yl)acetamide;

2-((3,5-Dicyano-6-(4-(dimethylamino)piperidin-1-yl)-4-ethylp yridin-2-yl)thio)-2-(4- fluorophenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl) pyridin-2-yl) thio)-2-(4- methylpyridin-2-yl) acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(3- methoxypyridin-2-yl)acetamide;

2-((3,5-Dicyano-6-(4-(dimethylamino)piperidin-1-yl)-4-ethylp yridin-2-yl)thio)-2-(2,4- difluorophenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1-yl )pyridin-2-yl)thio)-2-(5- fluoropyridin-2-yl)acetamide;

2-((3,5-Dicyano-4-ethoxy-6-(4-(2-hydroxyethyl)-1,4-diazepan- 1-yl)pyridin-2- yl)thio)propanamide;

2-((3,5-Dicyano-6-(4-(2-hydroxyethyl)-1,4-diazepan-1-yl)-4-p ropoxypyridin-2- yl)thio)-2-phenylacetamide; 2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(4- methoxypyridin-2-yl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(2-methyl-2,8-diazaspiro[4.5]decan -8-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-(4-(dimethylamino)piperidin-1-yl)-4-ethylp yridin-2-yl)thio)-2-(3,4- difluorophenyl)acetamide;

1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2- yl)piperidine-4-carboxamide;

2-((3,5-Dicyano-6-((2-(dimethylamino)ethyl)thio)-4-ethylpyri din-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-6-((3S,4R)-3,4-dihydroxypyrrolidin-1-yl)-4-e thylpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(3- fluoropyridin-2-yl) acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(5- methoxypyridin-2-yl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(1-hydroxy-2-methylpropan-2-yl) piperazin-1- yl)pyridin-2-yl)thio)-2-(4-fluorophenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(3- (trifluoromethyl)phenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(2-hydroxyethoxy)piperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl) pyridin-2-yl)thio)-2-(2- fluoropyridin-3-yl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl) pyridin-2-yl)thio)-2-(6- fluoropyridin-3-yl)acetamide;

3-((6-(2-Amino-2-oxo-1-phenylethylthio)-3,5-dicyano-4-ethylp yridin-2- yl)(methyl)amino)propanamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(oxetan-3-yloxy)piperidin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide; 2-((3,5-Dicyano-6-(4-((2,2-difluoroethyl) amino)-4-methylpiperidin-1-yl)-4- ethylpyridin-2-yl) thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(4- (trifluoromethyl)phenyl)acetamide;

2-((6-(4-Aminopiperazin-1-yl)-3,5-dicyano-4-ethylpyridin-2-y l)thio)-2- phenylacetamide;

2-((6-((2-Amino-2-oxoethyl)thio)-3,5-dicyano-4-ethylpyridin- 2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(pyrrolo[3,4-c]pyrazol-5(1H,4H,6H) -yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-(5-methoxypyridin-2- yl)acetamide;

2-((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-(5-methylpyridin-2- yl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(2- fluoropyridin-4-yl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-hydroxy-4-(hydroxymethyl)piperi din-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2-oxo-3-oxa-1,8-diazaspiro[4.5]de can-8-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((6-(4-Amino-4-(hydroxymethyl)piperidin-1-yl)-3,5-dicyano- 4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-(4-(Aminomethyl)-4-hydroxypiperidin-1-yl)-3,5-dicyano- 4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-(3-Benzoylphenyl)-2-((3,5-dicyano-4-ethyl-6-(4-(2-hydroxye thyl)-1,4-diazepan-1- yl)pyridin-2-yl)thio)acetamide;

2-(4-Benzoylphenyl)-2-((3,5-dicyano-4-ethyl-6-(4-(2-hydroxye thyl)-1,4-diazepan-1- yl)pyridin-2-yl)thio)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(2- methylpyridin-4-yl)acetamide; 2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(3- (pyrrolidin-1-yl)phenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(3- fluoropyridin-4-yl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(2,5- difluoropyridin-4-yl)acetamide;

2-((3,5-Dicyano-6-(4-(2,5-dioxoimidazolidin-1-yl)piperidin-1 -yl)-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

4-Amino-1-(6-((2-amino-2-oxo-1-phenylethyl) thio)-3, 5-dicyano-4-ethylpyridin-2-yl) piperidine-4-carboxamide;

2-((3,5-Dicyano-6-(4-(2,5-dioxopyrrolidin-1-yl)piperidin-1-y l)-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2- phenylacetamide (isomer 1);

2-((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2- phenylacetamide (Isomer 2) ;

2-((3,5-Dicyano-4-ethyl-6-(2-oxo-1-oxa-3,8-diazaspiro[4.5]de can-8-yl)pyridin-2- yl)thio)-2-phenylacetamide;

1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)-4- hydroxy piperidine-4-carboxamide;

1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)azetidin- 3-yl carbamate;

2-((3,5-Dicyano-6-(4-(2,4-dioxooxazolidin-3-yl)piperidin-1-y l)-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

3-((6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-2-hydroxy-2-methylpropanamide;

2-((3,5-Dicyano-4-ethyl-6-(3-(hydroxymethyl)azetidin-1-yl)py ridin-2-yl)thio)-2- phenylacetamide;

2-(3,5-Dicyano-4-ethyl-6-(piperazin-1-yl)pyridin-2-ylthio)-2 -(thiophen-3- yl)acetamide; 2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl) pyridin-2-yl) thio)-2-(5- methylpyridin-3-yl) acetamide;

2-((6-(4-(3-Amino-2-oxopyrrolidin-1-yl)piperidin-1-yl)-3,5-d icyano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)piperidin- 4-yl (2S)-2-amino-3-methylbutanoate;

2-((6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2-yl) (methyl) amino)ethyl (2S)-2-amino-3-methylbutanoate;

2,2'-((3,5-Dicyano-4-ethylpyridine-2,6-diyl)bis(sulfanediyl) )bis(2-phenylacetamide); (2S)-(1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4 –ethyl pyridin-2- yl)azetidin-3-yl)methyl 2-amino-3-methylbutanoate;

2-((6-(3-Aminoazetidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-yl )thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-methylpyridin-2-yl)thio)-2-phenyla cetamide;

N-(1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-et hylpyridin-2- yl)piperidin-4-yl)-2-hydroxyacetamide;

N-(1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-et hylpyridin-2- yl)azetidin-3-yl)-2-hydroxyacetamide;

2-((3-Cyano-4-ethyl-5-methyl-6-(piperazin-1-yl)pyridin-2-yl) thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(5-methyl-2,5-diazabicyclo[2.2.1]h eptan-2-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(2-(pyrrolidin-1-yl)ethyl)piper azin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-phenylacetamide-2- d;

(R)-2-((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)th io)-2- phenylacetamide-2-d;

2-((6-(4-(4-Bromobenzoyl)piperazin-1-yl)-3,5-dicyano-4-ethyl pyridin-2-yl)thio)-2- phenylacetamide; 2-((3,5-Dicyano-4-ethyl-6-(4-(2-hydroxyethyl)-1,4-diazepan-1 -yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-6-(4-cyanopiperidin-1-yl)-4-ethylpyridin-2-y l)thio)-2- phenylacetamide;

(S)-2-((3,5-Dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-Amino-4-methylpiperidin-1-yl)-3,5-dicyano-4-cyclopr opylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl)pyri din-2-yl)thio)-2-(pyridin- 2-yl)acetamide;

2-((3,5-Dichloro-4-ethyl-6-(piperazin-1-yl)pyridin-2-yl)thio )-2-phenylacetamide; tert-Butyl (1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)piperidin-4-yl)carbamate;

2-((6-(3-(2-Amino-2-oxoethyl)azetidin-1-yl)-3,5-dicyano-4-et hylpyridin-2-yl)thio)-2- phenylacetamide;

(2R)-1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4- ethylpyridin-2- yl)azetidin-3-yl 2-amino-3-methylbutanoate;

2-((3,5-Dicyano-4-ethyl-6-(methyl((5-oxo-4,5-dihydro-1H-1,2, 4-triazol-3- yl)methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-((6-(((4H-1,2,4-Triazol-3-yl)methyl)(methyl)amino)-3,5-dic yano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethoxy-6-methylpyridin-2-yl)thio)-2-phenyl acetamide;

2-((3,5-Dicyano-4,6-diethylpyridin-2-yl)thio)-2-phenylacetam ide;

2-((6-((2-(4H-1,2,4-Triazol-4-yl)ethyl)(methyl)amino)-3,5 -dicyano-4-ethylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((6-(((1H-Pyrazol-3-yl)methyl)(methyl)amino)-3,5-dicyano-4 -ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-(6,7-dihydro-1H-[1,2,3]triazolo[4,5-c]pyri din-5(4H)-yl)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide; 2-((6-(((1H-Imidazol-2-yl)methyl)(methyl)amino)-3,5-dicyano- 4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-(((1H-Imidazol-5-yl)methyl)(methyl)amino)-3,5-dicyano- 4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

(2R)-2-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5 -dicyano-4- ethylpyridin-2-yl)piperidin-4-yl)propanamide;

4-(2-Amino-1-((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan- 1-yl)pyridin-2- yl)thio)-2-oxoethyl)benzamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-hydroxypyrrolidin-1-yl)py ridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(3-hydroxypyrrolidin-1-yl)pyridin- 2-yl)thio)-2- phenylacetamide;

(2R)-2-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5 -dicyano-4- cyclopropyl pyridin-2-yl)piperidin-4-yl)propanamide;

2-((6-((2-Aminoethyl)(methyl)amino)-3,5-dicyano-4-cyclopropy lpyridin-2-yl)thio)-2- phenylacetamide;

2-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl) thio)-3,5-dicyano-4- cyclopropylpyridin-2-yl)piperidin-4-yl)-2-methylpropanamide;

4-(2-Amino-1-((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin- 2-yl)thio)-2- oxoethyl)benzamide;

2-(6-(4-Aminopiperidin-1-yl)-3-cyano-4-ethyl-5-methylpyridin -2-ylthio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(4-(N- methylsulfamoyl)phenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(6-fluoro-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2- phenylacetamide;

2-((6-(4-Amino-3,3-difluoropiperidin-1-yl)-3,5-dicyano-4-eth ylpyridin-2-yl)thio)-2- phenylacetamide;

tert-Butyl (1-(6-((2-amino-2-oxo-1-phenylethyl) thio)-3,5-dicyano-4-ethylpyridin-2- yl)-3,3-difluoropiperidin-4-yl) carbamate; 2-((3,5-Dicyano-4-cyclopropyl-6-((2-hydroxyethyl)(methyl)ami no)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-hydroxyazetidin-1-yl)pyri din-2-yl)thio)-2- phenylacetamide;

1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2- yl)pyrrolidine-3-carboxamide;

2-((6-((3-Aminopropyl) (methyl) amino)-3, 5-dicyano-4-cyclopropylpyridin-2-yl) thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-((2-(3-hydroxyazetidin-1-yl) -2- oxoethyl)(methyl)amino) pyridin-2-yl)thio)-2-phenylacetamide;

2-((6-(4-((2-Amino-2-oxoethyl)amino)piperidin-1-yl)-3,5-dicy ano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-((2-Amino-2-oxoethyl)(methyl)amino)-3,5-dicyano-4-cycl opropylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-((2-Amino-2-oxo-1-phenylethyl) thio)-3, 5-dicyano-4-cyclopropylpyridin-2- yl)(methyl)amino)ethyl carbamate;

(2R)-2-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5 -dicyano-4- ethylpyridin-2-yl)piperidin-4-yl)-3-hydroxypropanamide;

(2S)-2-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl) thio)-3, 5-dicyano-4- ethylpyridin-2-yl) piperidin-4-yl)-3-hydroxypropanamide;

2-(4-(2-Amino-2-oxoethyl)phenyl)-2-(3,5-dicyano-4-ethyl-6-(4 -methyl-1,4- diazepan-1-yl)pyridin-2-ylthio)acetamide;

2-(4-(2-Amino-2-oxoethyl)phenyl)-2-(3,5-dicyano-6-(dimethyla mino)-4-ethylpyridin- 2-ylthio)acetamide;

2-((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-(4-(N- methylsulfamoyl)phenyl)acetamide;

2-((3,5-Dicyano-6-(dimethylamino-d 6 )-4-ethylpyridin-2-yl)thio)-2-phenylacetamide; (R)-2-((3,5-Dicyano-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin- 1-yl)pyridin-2-yl)thio)-2- phenylacetamide; (R)-2-((3,5-Dicyano-6-(4-(dimethylamino)piperidin-1-yl)-4-et hylpyridin-2-yl)thio)-2- phenylacetamide;

2-(3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-ylthio)-2- (3-(2- (dimethylamino)ethoxy)phenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(neopentylamino)piperidin-1-yl) pyridin-2-yl)thio)-2-(4- fluorophenyl)acetamide;

2-((3,5-dicyano-4-ethyl-6-(3-fluoro-4-A(neopentylamino)piper idin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-y l)thio)-2-(4- (trifluoromethyl)phenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide;

(R)-2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin -2-yl)thio)-2- phenylacetamide;

2-((6-((2-amino-2-oxoethyl)(methyl)amino)-3,5-dicyano-4-ethy lpyridin-2-yl)thio)-2- phenylacetamide; (single enantiomer)

(3S)-1-(6-((2-amino-2-oxo-1-phenylethyl) thio)-3, 5-dicyano-4-ethylpyridin-2-yl) Pyrrolidin-3-yl dihydrogen phosphate;

(3R)-1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4- ethylpyridin-2- yl)pyrrolidin-3-yl dihydrogen phosphate;

(S)-1-(6-(((S)-2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano -4-ethylpyridin-2- yl)pyrrolidin-3-yl dihydrogen phosphate;

(S)-1-(6-(((R)-2-amino-2-oxo-1-phenylethyl) thio)-3,5-dicyano-4-ethylpyridin-2-yl) pyrrolidin-3-yl dihydrogen phosphate;

2-((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-(3- (dimethylphosphoryl)phenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl)pyri din-2-yl)thio)-2-(3-( dimethylphosphoryl)phenyl)acetamide;

(R)-2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4- ethylpyridin-2- yl)(methyl)amino)ethyl dihydrogen phosphate; (R)-2-((3,5-dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl)thio)-2-(4- methoxyphenyl)acetamide;

(R)-2-(4-chlorophenyl)-2-((3,5-dicyano-4-ethyl-6-((S)-3-hydr oxypyrrolidin-1- yl)pyridin-2-yl)thio)acetamide;

(R)-2-((3,5-dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl)thio)-2-(4- fluoro phenyl)acetamide;

(S)-1-(6-(((R)-2-amino-1-(4-fluorophenyl)-2-oxoethyl)thio)-3 ,5-dicyano-4- ethylpyridin-2-yl)pyrrolidin-3-yl dihydrogen phosphate;

2-((3, 5-dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl) thio)-2-(4- fluorophenyl) acetamide;

2-((3,5-dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl) thio)-2-(2, 6- difluorophenyl) acetamide;

2-((3, 5-dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl) thio)-2-(2, 3- difluorophenyl) acetamide;

2-((3, 5-dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl) thio)-2-(2, 4- difluorophenyl) acetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((S)-2-(hydroxymethyl)pyrrolidi n-1-yl)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((2-hydroxyethyl)(methyl)amino) piperidin-1-yl)pyridin- 2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((2-hydroxy-2-methylpropyl)(met hyl)amino)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(pyrrolidin-1-ylmethyl)piperidi n-1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((2-methoxy-2-methylpropyl)amin o)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((2-hydroxy-2-methylpropyl)amin o)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(4-(cyclobutylamino)piperidin-1-yl)-4-ethy lpyridin-2-yl)thio)-2- phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-(4-(((3-methyloxetan-3-yl)methyl)a mino)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(4-methylpiperazin-1-yl)piperid in-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((R)-2-methylpyrrolidin-1-yl)pi peridin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(4-((2R,5S)-2,5-dimethylpyrrolidin-1-yl)pi peridin-1-yl)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((S)-2-methylpyrrolidin-1-yl)pi peridin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(4-(cyclobutyl(methyl)amino)piperidin-1-yl )-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-(6-(4-(benzylamino)piperidin-1-yl)-3,5-dicyano-4-ethylpyri din-2-ylthio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(((6-methoxypyridin-2-yl)methyl )amino)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((S)-3-fluoropyrrolidin-1-yl)pi peridin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(methyl(2-((R)-2-methylpyrrolidin- 1- yl)ethyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((R)-3-fluoropyrrolidin-1-yl)pi peridin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(4-((2S,5S)-2,5-dimethylpyrrolidin-1-yl)pi peridin-1-yl)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(methyl(2-((S)-2-methylpyrrolidin- 1- yl)ethyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((R)-2-(hydroxymethyl)pyrrolidi n-1-yl)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(4-(dimethylamino)piperidin-1-yl)-4-ethylp yridin-2-yl)thio)-2-(4- fluorophenyl)acetamide; 2-((3,5-dicyano-4-ethyl-6-(4-(((1-methylcyclobutyl)methyl)am ino)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(((6-methoxypyridin-3-yl)methyl )amino)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-(3,5-dicyano-4-ethyl-6-((2-(ethylamino)ethyl)(methyl)amino )pyridin-2-ylthio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((4-methylpiperazin-1-yl)methyl )piperidin-1-yl)pyridin- 2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(methyl(2-(methylamino)ethyl)amino )pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-6-(4-((2R,5R)-2,5-dimethylpyrrolidin-1-yl)pi peridin-1-yl)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(((1-methylcyclopropyl)methyl)a mino)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((4-fluorobenzyl)amino)piperidi n-1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((S)-2-(hydroxymethyl)pyrrolid in-1- yl)ethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-(3,5-dicyano-6-((2-((2S,5R)-2,5-dimethylpyrrolidin-1-yl)et hyl)(methyl)amino)-4- ethylpyridin-2-ylthio)-2-phenylacetamide;

2-((6-((2-(azepan-1-yl)ethyl)(methyl)amino)-3,5-dicyano-4-et hylpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(methyl(2-(piperidin-1-yl)ethyl)am ino)pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((R)-2-(hydroxymethyl)pyrrolid in-1- yl)ethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-(3,5-dicyano-4-ethyl-6-((2-(ethyl(methyl)amino)ethyl)(meth yl)amino)pyridin-2- ylthio)-2-phenylacetamide;

2-((3,5-dicyano-6-((2-((2R,5R)-2,5-dimethylpyrrolidin-1-yl)e thyl)(methyl)amino)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide; 2-(3,5-dicyano-4-ethyl-6-((2-((S)-3-hydroxypyrrolidin-1- yl)ethyl)(methyl)amino)pyridin-2-ylthio)-2-phenylacetamide;

methyl 2-((1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-e thylpyridin-2- yl)piperidin-4-yl)amino)-2-methylpropanoate;

2-((3,5-dicyano-4-ethyl-6-(methyl(2-(neopentylamino)ethyl)am ino)pyridin-2- yl)thio)-2-phenylacetamide;

2-(3,5-dicyano-4-ethyl-6-(methyl(2-(1-methylcyclopropylamino )ethyl)amino)pyridin- 2-ylthio)-2-phenylacetamide;

2-((3,5-dicyano-6-((2-((2S,5S)-2,5-dimethylpyrrolidin-1-yl)e thyl)(methyl)amino)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((2-methoxyethyl)amino)ethyl)( methyl)amino)pyridin- 2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((2-methoxy-2-methylpropyl)(met hyl)amino)piperidin- 1-yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-((2-(dimethylamino)ethyl)(methyl)amino)-4- ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-(3,5-dicyano-4-ethyl-6-((2-((R)-3-hydroxypyrrolidin-1- yl)ethyl)(methyl)amino)pyridin-2-ylthio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((2-fluoroethyl)amino)ethyl)(m ethyl)amino)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(4-(3,3-difluoropyrrolidin-1-yl)piperidin- 1-yl)-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-e thylpyridin-2- yl)piperidin-4-yl)amino)acetic acid;

2-((6-((3-aminocyclobutyl)(methyl)amino)-3,5-dicyano-4-ethyl pyridin-2-yl)thio)-2- phenylacetamide;

(R)-2-(3,5-dicyano-4-ethyl-6-(methyl((R)-tetrahydrofuran-3-y l)amino)pyridin-2- ylthio)-2-phenylacetamide;

(S)-2-(3,5-dicyano-4-ethyl-6-(methyl((R)-tetrahydrofuran-3-y l)amino)pyridin-2- ylthio)-2-phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-(4-morpholinopiperidin-1-yl)pyridi n-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(2-hydroxyethyl)-3-oxopiperazin -1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1-yl )pyridin-2-yl)thio)-2-(4- fluorophenyl)acetamide;

(R)-2-((6-((3S,4R)-4-amino-3-fluoropiperidin-1-yl)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(3-fluoro-4-(methylamino)piperidin -1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

rel-2-((6-(trans)-4-amino-3-fluoropiperidin-1-yl)-3,5-dicyan o-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

(R)-2-((6-((3R,4S)-4-amino-3-fluoropiperidin-1-yl)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(3-fluoro-4-((2-methoxyethyl)amino )piperidin-1-yl)pyridin- 2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(methyl(2-(pyrrolidin-1-yl)ethyl)a mino)pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-6-(3-((dimethylamino)methyl)pyrrolidin-1-yl) -4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((2-hydroxy-2-methylpropyl)amin o)piperidin-1- yl)pyridin-2-yl)thio)-2-(4-fluorophenyl)acetamide;

(R)-2-((6-((3S,4R)-4-amino-3-hydroxypiperidin-1-yl)-3,5-dicy ano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-((2-(diethylamino)ethyl)(methyl)amino)-4-e thylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-6-((2-((R)-3-(dimethylamino)pyrrolidin-1-yl) ethyl)(methyl)amino)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-((2-((S)-3-(dimethylamino)pyrrolidin-1-yl) ethyl)(methyl)amino)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide; (R)-2-((6-((3R,4R)-4-amino-3-fluoropiperidin-1-yl)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

(R)-2-((6-((3S,4S)-4-amino-3-fluoropiperidin-1-yl)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(3-(methylamino)pyrrolidin-1-yl)py ridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-y l)thio)-2-(4- fluorophenyl)acetamide;

(R)-2-((6-((3R,4R)-4-amino-3-hydroxypiperidin-1-yl)-3,5-dicy ano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-((R)-3-aminopyrrolidin-1-yl)-3,5-dicyano-4-ethylpyridi n-2-yl)thio)-2- phenylacetamide;

2-((6-(3-(aminomethyl)pyrrolidin-1-yl)-3,5-dicyano-4-ethylpy ridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(methylamino)piperidin-1-yl)pyr idin-2-yl)thio)-2-(4- fluorophenyl)acetamide;

2-((3,5-dicyano-6-(4-(cyclopropylamino)-3-fluoropiperidin-1- yl)-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-((S)-3-aminopyrrolidin-1-yl)-3,5-dicyano-4-ethylpyridi n-2-yl)thio)-2- phenylacetamide;

2-((6-((2-((R)-3-aminopyrrolidin-1-yl)ethyl)(methyl)amino)-3 ,5-dicyano-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

3,5-dicyano-6-((R)-3-(dimethylamino)pyrrolidin-1-yl)-4-ethyl pyridin-2-yl)thio)-2-(4- fluorophenyl)acetamide;

(S)-2-((6-((3S,4R)-4-amino-3-fluoropiperidin-1-yl)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(neopentylamino)piperidin-1-yl) pyridin-2-yl)thio)-2-(4- (trifluoromethyl)phenyl)acetamide;

tert-butyl ((3S,4R)-1-(6-(((R)-2-amino-2-oxo-1-phenylethyl)thio)-3,5-di cyano-4- ethylpyridin-2-yl)-3-hydroxypiperidin-4-yl)carbamate; rel-tert-butyl (cis)-1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4 - ethylpyridin-2-yl)-3-fluoropiperidin-4-yl)carbamate;

2-((6-((2-((S)-3-aminopyrrolidin-1-yl)ethyl)(methyl)amino)-3 ,5-dicyano-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-((R)-3-(dimethylamino)pyrrolidin-1-yl)-4-e thylpyridin-2-yl)thio)-2- phenylacetamide;

tert-butyl ((3R,4S)-1-(6-(((R)-2-amino-2-oxo-1-phenylethyl)thio)-3,5-di cyano-4- ethylpyridin-2-yl)-3-hydroxypiperidin-4-yl)carbamate;

rel-tert-butyl (cis)-1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4 - ethylpyridin-2-yl)-3-fluoropiperidin-4-yl)carbamate;

2-((3,5-dicyano-6-((S)-3-(dimethylamino)pyrrolidin-1-yl)-4-e thylpyridin-2-yl)thio)-2- phenylacetamide;

(S)-2-((6-((3R,4S)-4-amino-3-fluoropiperidin-1-yl)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((S)-3-((2-hydroxy-2-methylpropyl) amino)pyrrolidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

tert-butyl ((3R,4R)-1-(6-(((R)-2-amino-2-oxo-1-phenylethyl)thio)-3,5-di cyano-4- ethylpyridin-2-yl)-3-hydroxypiperidin-4-yl)carbamate;

2-((3,5-dicyano-6-((S)-3-(dimethylamino)pyrrolidin-1-yl)-4-e thylpyridin-2-yl)thio)-2- (4-fluorophenyl)acetamide;

rel-2-((6-cis-4-amino-3-fluoropiperidin-1-yl)-3,5-dicyano-4- ethylpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(methylamino)piperidin-1-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-6-(4-(dimethylamino)piperidin-1-yl)-4-ethylp yridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(ethyl(methyl)amino)piperidin-1 -yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(neopentylamino)piperidin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-(4-(methyl(neopentyl)amino)piperid in-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(4-(cyclopropylamino)piperidin-1-yl)-4-eth ylpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((2-methoxyethyl)amino)piperidi n-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(4-((2,2-difluoroethyl)amino)piperidin-1-y l)-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((R)-2-((neopentylamino)methyl)mor pholino)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(2-((dimethylamino)methyl)morpholino)-4-et hylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-6-(2-((diethylamino)methyl)morpholino)-4-eth ylpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(2-(pyrrolidin-1-ylmethyl)morpholi no)pyridin-2-yl)thio)-2- phenylacetamide;

(R)-2-((6-((R)-2-(aminomethyl)morpholino)-3,5-dicyano-4-ethy lpyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(2-(aminomethyl)morpholino)-3,5-dicyano-4-ethylpyridin -2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(2-((methylamino)methyl)morpholino )pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-((R)-2-(aminomethyl)morpholino)-3,5-dicyano-4-ethylpyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-6-(3-((dimethylamino)methyl)piperidin-1-yl)- 4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(3-((methylamino)methyl)piperidin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((S)-2-((neopentylamino)methyl)mor pholino)pyridin-2- yl)thio)-2-phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-((S)-3-((neopentylamino)methyl)pip eridin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-amino-N-(((2S)-4-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3, 5-dicyano-4- ethylpyridin-2-yl)morpholin-2-yl)methyl)-2-methylpropanamide ;

2-((6-((S)-3-(aminomethyl)piperidin-1-yl)-3,5-dicyano-4-ethy lpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-6-((R)-2-((diethylamino)methyl)morpholino)-4 -ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-amino-N-(((2R)-4-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3, 5-dicyano-4- ethylpyridin-2-yl)morpholin-2-yl)methyl)-2-methylpropanamide ;

2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-y l)thio)-2-(3- fluoropyridin-2-yl)acetamide;

2-((6-((S)-2-(aminomethyl)morpholino)-3,5-dicyano-4-ethylpyr idin-2-yl)thio)-2- phenylacetamide;

2-amino-N-(((3S)-1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3, 5-dicyano-4- ethylpyridin-2-yl)piperidin-3-yl)methyl)-2-methylpropanamide ;

2-amino-N-(((3S)-1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3, 5-dicyano-4- ethylpyridin-2-yl)piperidin-3-yl)methyl)acetamide;

2-amino-N-(((2R)-4-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3, 5-dicyano-4- ethylpyridin-2-yl)morpholin-2-yl)methyl)acetamide;

2-((6-((R)-3-(aminomethyl)piperidin-1-yl)-3,5-dicyano-4-ethy lpyridin-2-yl)thio)-2-(4- fluorophenyl)acetamide;

2-((3,5-dicyano-4-ethyl-6-((R)-3-((neopentylamino)methyl)pip eridin-1-yl)pyridin-2- yl)thio)-2-(4-fluorophenyl)acetamide;

2-amino-N-(((2S)-4-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3, 5-dicyano-4- ethylpyridin-2-yl)morpholin-2-yl)methyl)acetamide;

N-(((R)-4-(6-(((R)-2-amino-2-oxo-1-phenylethyl)thio)-3,5-dic yano-4-ethylpyridin-2- yl)morpholin-2-yl)methyl)-2-hydroxyacetamide;

(S)-2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin -2-yl)thio)-2- phenylacetamide; 2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-(2-hydroxyethyl)-N-methylacetamide;

2-((3,5-dicyano-4-ethyl-6-((S)-3-(methylamino)piperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-amino-4-methylpiperidin-1-yl)-3,5-dicyano-4-ethylpy ridin-2-yl)thio)-2- phenylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-((1-(hydroxymethyl)cyclopropyl)methyl)-N -methylacetamide;

2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4- cyclopropylpyridin-2-yl)azetidin-3-yl)acetamide;

(2S)-2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5 -dicyano-4- cyclopropylpyridin-2-yl)azetidin-3-yl)-3-hydroxypropanamide;

2-((6-((S)-3-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin -2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((R)-3-hydroxypyrrolidin-1-yl) -2- oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

(2R)-2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5 -dicyano-4- cyclopropylpyridin-2-yl)azetidin-3-yl)-3-hydroxypropanamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-(3-hydroxy-2,2-dimethylpropyl)-N-methyla cetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((S)-3-hydroxypyrrolidin-1-yl) -2- oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-((6-(4-amino-4-methylpiperidin-1-yl)-3,5-dicyano-4-ethylpy ridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-(aminomethyl)-4-fluoropiperidin-1-yl)-3,5-dicyano-4 -ethylpyridin-2-yl)thio)- 2-phenylacetamide hydrochloride;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-cycl opropylpyridin-2- yl)(methyl)amino)-N-(2-aminoethyl)acetamide hydrochloride;

2-((3,5-dicyano-4-ethyl-6-(methyl(2-oxo-2-(pyrrolidin-1-yl)e thyl)amino)pyridin-2- yl)thio)-2-phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-((2-(4-hydroxypiperidin-1-yl)-2- oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(methyl(2-oxo-2-(piperazin-1-yl)et hyl)amino)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(methyl(2-morpholino-2-oxoethyl)am ino)pyridin-2- yl)thio)-2-phenylacetamide;

(R)-2-((6-((S)-3-(aminomethyl)-3-hydroxypyrrolidin-1-yl)-3,5 -dicyano-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((S)-3-(guanidinooxy)pyrrolidin-1- yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-amino-N-(2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dic yano-4-ethylpyridin-2- yl)(methyl)amino)ethyl)-2-methylpropanamide;

2-((6-((2-(2-aminoethoxy)ethyl)(methyl)amino)-3,5-dicyano-4- ethylpyridin-2- yl)thio)-2-phenylacetamide;

4-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)butanamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-(2-aminoethyl)acetamide;

2-((6-((2-(azetidin-1-yl)-2-oxoethyl)(methyl)amino)-3,5-dicy ano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-((R)-3-(aminomethyl)-3-fluoropyrrolidin-1-yl)-3,5-dicy ano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-(3-hydroxyazetidin-1-yl)-2- oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(guanidinooxy)piperidin-1-yl)py ridin-2-yl)thio)-2- phenylacetamide;

2-((6-(3-aminoazetidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-yl )thio)-2- phenylacetamide; (single stereoisomer)

2-((3,5-dicyano-4-ethyl-6-((R)-3-(methylamino)piperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-((2-((3R,4S)-3-hydroxy-4-(hydroxym ethyl)pyrrolidin-1-yl)- 2-oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamid e;

(R)-2-((6-((S)-3-(aminomethyl)-3-fluoropyrrolidin-1-yl)-3,5- dicyano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-cycl opropylpyridin-2- yl)(methyl)amino)-N-(1,3-dihydroxypropan-2-yl)acetamide;

2-((3,5-dicyano-4-ethyl-6-((S)-3-(oxetan-3-ylamino)piperidin -1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-cycl opropylpyridin-2- yl)(methyl)amino)-N,N-bis(2-hydroxyethyl)acetamide;

2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4- cyclopropylpyridin-2-yl)piperidin-4-yl)acetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((2-hydroxyethyl)amino)-4-methy lpiperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-(guanidinooxy)ethyl)(methyl)am ino)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((6-(4-((2-aminoethyl)amino)piperidin-1-yl)-3,5-dicyano-4- ethylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((S)-2-(hydroxymethyl)morpholi no)-2- oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-((2-((cis)-3,4-dihydroxypyrrolidin-1-yl)-2 - oxoethyl)(methyl)amino)-4-ethylpyridin-2-yl)thio)-2-phenylac etamide;

2-((3,5-dicyano-4-ethyl-6-((2-((S)-3-(hydroxymethyl)pyrrolid in-1-yl)-2- oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((3S,4S)-3-hydroxy-4-(hydroxym ethyl)pyrrolidin-1-yl)- 2-oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamid e;

2-((3,5-dicyano-4-ethyl-6-((S)-3-(neopentylamino)piperidin-1 -yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((R)-3-(hydroxymethyl)pyrrolid in-1-yl)-2- oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide; 2-((3,5-dicyano-6-((2-((3R,4R)-3,4-dihydroxypyrrolidin-1-yl) -2- oxoethyl)(methyl)amino)-4-ethylpyridin-2-yl)thio)-2-phenylac etamide;

(R)-2-((3,5-dicyano-4-ethyl-6-((S)-3-hydroxy-3-(hydroxymethy l)pyrrolidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

(2S)-2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5 -dicyano-4- cyclopropylpyridin-2-yl)piperidin-4-yl)propanamide;

2-((6-(4-(2-aminoethoxy)piperidin-1-yl)-3,5-dicyano-4-cyclop ropylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(4-((2-hydroxyethyl)amino)pi peridin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-(1,3-dihydroxypropan-2-yl)acetamide;

2-((3,5-dicyano-6-((2-((3R,5S)-3,5-dihydroxypiperidin-1-yl)- 2- oxoethyl)(methyl)amino)-4-ethylpyridin-2-yl)thio)-2-phenylac etamide;

2-((3,5-dicyano-6-((2-((3S,4S)-3,4-dihydroxypyrrolidin-1-yl) -2- oxoethyl)(methyl)amino)-4-ethylpyridin-2-yl)thio)-2-phenylac etamide;

2-((3,5-dicyano-4-ethyl-6-(4-((2-hydroxyethyl)amino)-4-(hydr oxymethyl)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((R)-2-(hydroxymethyl)morpholi no)-2- oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-methoxyacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((3R,4R)-3-hydroxy-4-(hydroxym ethyl)pyrrolidin-1-yl)- 2-oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamid e;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-(3-hydroxypropyl)-N-methylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-((R)-2,3-dihydroxypropyl)acetamide;

2-((6-(4-((2-amino-2-oxoethyl)amino)piperidin-1-yl)-3,5-dicy ano-4- cyclopropylpyridin-2-yl)thio)-2-phenylacetamide; 2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N,N-bis(2-hydroxyethyl)acetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-(2-hydroxyethyl)acetamide;

2-((6-((3-aminopropyl)(methyl)amino)-3,5-dicyano-4-ethylpyri din-2-yl)thio)-2- phenylacetamide;

2-((6-(3-(aminomethyl)azetidin-1-yl)-3,5-dicyano-4-ethylpyri din-2-yl)thio)-2- phenylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-((1-(hydroxymethyl)cyclopropyl)methyl)ac etamide;

(R)-2-((3,5-dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl)thio)-2-(2,4- difluorophenyl)acetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-(3-(hydroxymethyl)oxetan-3-yl)acetamide;

2-((3,5-dicyano-4-ethyl-6-(3-(guanidinooxy)azetidin-1-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-(3-hydroxypropyl)acetamide;

2-((3,5-dicyano-6-(4-(2,3-dihydroxypropyl)-1,4-diazepan-1-yl )-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-hydroxyacetamide;

3-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4- cyclopropylpyridin-2-yl)azetidin-3-yl)oxetane-3-carboxamide;

2-((3,5-dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl)pyri din-2-yl)thio)-2-(2- fluorophenyl)acetamide;

2-((3,5-dicyano-6-((S)-3-(cyclopropylamino)piperidin-1-yl)-4 -ethylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-(3-hydroxy-2,2-dimethylpropyl)acetamide; N-(2-(4H-1,2,4-triazol-4-yl)ethyl)-2-((6-((2-amino-2-oxo-1-p henylethyl)thio)-3,5- dicyano-4-ethylpyridin-2-yl)(methyl)amino)acetamide;

N1-(2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4- ethylpyridin-2- yl)(methyl)amino)ethyl)oxalamide;

2-((6-(3-(aminomethyl)-3-fluoroazetidin-1-yl)-3,5-dicyano-4- ethylpyridin-2-yl)thio)- 2-phenylacetamide;

(R)-2-((3,5-dicyano-4-ethyl-6-((R)-3-hydroxy-3-(hydroxymethy l)pyrrolidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-((S)-3-((2,2-difluoroethyl)amino)piperidin -1-yl)-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-((R)-3-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin -2-yl)thio)-2- phenylacetamide;

2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-methoxypyridin-2 -yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((S)-4-hydroxyisoxazolidin-2-yl)py ridin-2-yl)thio)-2- phenylacetamide;

(R)-2-((3,5-dicyano-4-ethyl-6-((3-hydroxypropyl)(methyl)amin o)pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-6-((S)-3-hydroxypyrrolidin-1-yl)-4-methoxypy ridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(3-methoxyazetidin-1-yl)piperid in-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(3-methoxyazetidin-1-yl)piperid in-1-yl)pyridin-2- yl)thio)-2-(4-fluorophenyl)acetamide;

(R)-2-((3,5-dicyano-4-ethyl-6-((2-hydroxyethyl)(methyl)amino )pyridin-2-yl)thio)-2- phenylacetamide;

(R)-2-((6-((R)-3-(aminomethyl)-3-hydroxypyrrolidin-1-yl)-3,5 -dicyano-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-(4-(cyclobutyl(methyl)amino)piperidin-1-yl )-4-ethylpyridin-2- yl)thio)-2-(4-fluorophenyl)acetamide; and 2-((3,5-dicyano-4-ethyl-6-(methyl(1-methylpyrrolidin-3-yl)am ino)pyridin-2-yl)thio)- 2-phenylacetamide; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably, presently invented novel compounds of Formula (IVbbr) are selected from: 2-{[3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl]sulfan yl}-2-phenylacetamide; 2-((3,5-dicyano-4-cyclopropyl-6-(1,4-diazepan-1-yl)pyridin-2 -yl)thio)-2- phenylacetamide;

2-{[3,5-dicyano-4-cyclopropyl-6-(4-ethyl-1,4-diazepan-1-yl)p yridin-2-yl]sulfanyl}-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-propyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2- phenylacetamide;

2-{[3,5-dicyano-4-ethyl-6-(4-ethyl-1,4-diazepan-1-yl)pyridin -2-yl]sulfanyl}-2- phenylacetamide;

2-{[3,5-dicyano-4-ethyl-6-(5-oxo-1,4-diazepan-1-yl)pyridin-2 -yl]sulfanyl}-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-morpholinopyridin-2-yl)thio) -2-(pyridin-4- yl)acetamide;

2-{[3,5-dicyano-4-ethyl-6-(4-methyl-3-oxopiperazin-1-yl)pyri din-2-yl]sulfanyl}-2- (pyridin-4-yl)acetamide;

2-[(3,5-dicyano-4-ethyl-6-{methyl[2-(morpholin-4-yl)ethyl]am ino}pyridin-2- yl)sulfanyl]-2-phenylacetamide;

2-{[3,5-dicyano-4-ethyl-6-(4-propylpiperazin-1-yl)pyridin-2- yl]sulfanyl}-2- phenylacetamide;

2-({3,5-dicyano-4-ethyl-6-[4-(piperidin-4-yl)piperazin-1-yl] pyridin-2-yl}sulfanyl)-2- phenylacetamide;

2-({3,5-dicyano-4-cyclopropyl-6-[3-(hydroxymethyl)piperazin- 1-yl]pyridin-2- yl}sulfanyl)-2-phenylacetamide; 2-{[3,5-dicyano-4-cyclopropyl-6-(3-oxopiperazin-1-yl)pyridin -2-yl]sulfanyl}-2- phenylacetamide;

2-({3,5-dicyano-4-cyclopropyl-6-[4-(morpholin-4-yl)piperidin -1-yl]pyridin-2- yl}sulfanyl)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(2,8-diazaspiro[4.5]decan-8-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-(dimethylamino)piperidin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-methylpiperazin-1-yl)pyri din-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(2-(hydroxymethyl)morpholino )pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(2,6-dimethylmorpholino)pyri din-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-(dimethylamino)piperidin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((6-(4-(Aminomethyl)-4-hydroxypiperidin-1-yl)-3,5-dicyano- 4-cyclopropylpyridin- 2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(3-(methylamino)piperidin-1- yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(3-aminopiperidin-1-yl)-3,5-dicyano-4-cyclopropylpyrid in-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(dimethylamino)pyridin-2-yl) thio)-2-(pyridin-4- yl)acetamide;

2-((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-(pyridin-4- yl)acetamide;

2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-cyclopropylpyrid in-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(4-(dimethylamino)piperidin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide; 2-((3,5-dicyano-4-cyclopropyl-6-(piperazin-1-yl)pyridin-2-yl )thio)-2-(pyridin-4- yl)acetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(1,4-diazepan-1-yl)pyridin-2 -yl)thio)-2-(pyridin-4- yl)acetamide;

2-((3,5-dicyano-4-cyclopropyl-6-((R)-3-hydroxypiperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide;

2-(3,5-dicyano-4-cyclopropyl-6-((S)-3-hydroxypiperidin-1-yl) pyridin-2-ylthio)-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-((S)-3-hydroxypyrrolidin-1-y l)pyridin-2-yl)thio)-2- (pyridin-4-yl)acetamide;

2-((3,5-dicyano-4-ethyl-6-(4-ethylpiperazin-1-yl)pyridin-2-y l)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(1-oxa-6-azaspiro[3.4]octan-6-yl)p yridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-(3-aminopropyl)piperazin-1-yl)-3,5-dicyano-4-ethylp yridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(1,7-diazaspiro[3.5]nonan-1-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-(pyrrolidin-1-ylmethyl)pi peridin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-(4-methylpiperazin-1-yl)p iperidin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

(R)-2-((3,5-dicyano-6-(1,4-diazepan-1-yl)-4-ethylpyridin-2-y l)amino)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-(pyrrolidin-1-yl)piperidi n-1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2,7-diazaspiro[3.5]nonan-7-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2,6-diazaspiro[3.4]octan-6-yl)pyr idin-2-yl)thio)-2- phenylacetamide; 2-((3,5-dicyano-4-cyclopropyl-6-(1,4-diazepan-1-yl)pyridin-2 -yl)thio)propanamide; 2-((3,5-Dicyano-4-ethyl-6-(4-(2-oxoimidazolidin-1-yl)piperid in-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-hydroxypiperidin-1-yl)pyridin-2 -yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl)pyri din-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(3-oxopiperazin-1-yl)pyridin-2-yl) thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((2-methoxyethyl)(methyl)amino)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(3-methoxyazetidin-1-yl)pyridin-2- yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(piperazin-1-yl)pyridin-2-yl)thio) -2-phenylacetamide; 2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-morpholinopyridin-2-yl)thio)-2-phe nylacetamide;

2-[[6-(azetidin-1-yl)-3,5-dicyano-4-ethyl-2-pyridyl]sulfanyl ]-2-phenyl-acetamide; 2-((3,5-dicyano-4-ethyl-6-(4-oxopiperidin-1-yl)pyridin-2-yl) thio)-2-phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-(1'-(2-hydroxyethyl)-[4,4'-bipiper idin]-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-((3S,5R)-3,5-dimethylpiperazin-1-yl)-4-eth ylpyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(8-azabicyclo[3.2.1]octan-3-yl(methyl)amino)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(2-(hydroxymethyl)morpholino )pyridin-2-yl)thio)-2- phenylacetamide;

(R)-2-((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)th io)-2-phenylacetamide; (R)-2-[(3,5-Dicyano-4-ethyl-6-morpholino-2-pyridyl)sulfanyl] -2-phenyl-acetamide; 2-{[3,5-dicyano-4-ethyl-6-(5-methyl-1,4-diazepan-1-yl)pyridi n-2-yl]sulfanyl}-2- phenylacetamide;

2-({3,5-Dicyano-4-ethyl-6-[4-(2-methoxyethyl)-1,4-diazepan-1 -yl]pyridin-2- yl}sulfanyl)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(2-hydroxypropyl)-1,4-diazepan- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

Methyl 2-[4-(6-{[carbamoyl(phenyl)methyl]sulfanyl}-3,5-dicyano-4-et hylpyridin-2- yl)-1,4-diazepan-1-yl]acetate;

2-{[3,5-Dicyano-4-cyclopropyl-6-(4-methyl-5-oxo-1,4-diazepan -1-yl)pyridin-2- yl]sulfanyl}-2-phenylacetamide;

2-{[3,5-Dicyano-4-cyclopropyl-6-(5-oxo-1,4-diazepan-1-yl)pyr idin-2-yl]sulfanyl}-2- phenylacetamide;

2-{[3,5-Dicyano-4-ethyl-6-(4-methyl-5-oxo-1,4-diazepan-1-yl) pyridin-2-yl]sulfanyl}- 2-phenylacetamide;

2-{[3,5-Dicyano-6-(1,4-diazepan-1-yl)-4-ethylpyridin-2-yl]su lfanyl}-2- phenylacetamide;

2-({3,5-Dicyano-6-[4-(2-hydroxyethyl)-1,4-diazepan-1-yl]-4-( 2,2,2- trifluoroethyl)pyridin-2-yl}sulfanyl)-2-phenylacetamide;

(2R)-2-({3,5-Dicyano-4-ethyl-6-[4-(2-hydroxyethyl)-1,4-diaze pan-1-yl]pyridin-2- yl}amino)-2-phenylacetamide;

2-({6-[(3S)-3-Aminopyrrolidin-1-yl]-3,5-dicyano-4-cyclopropy lpyridin-2-yl}sulfanyl)- 2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2,9-diazaspiro[5.5]undecan-9-yl)p yridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(hexahydro-1H-pyrrolo[1,2-a][1,4]d iazepin-2(3H)- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2-methyl-2,9-diazaspiro[5.5]undec an-9-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-(2-(cyclopropylmethyl)-2,9-diazaspiro[5.5] undecan-9-yl)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide; 2-((3,5-Dicyano-6-(4-(3-(dimethylamino)propyl)piperazin-1-yl )-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(pyrrolidin-3-yl)piperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-([4,4'-Bipiperidin]-1-yl)-3,5-dicyano-4-ethylpyridin-2 -yl)thio)-2- phenylacetamide;

2-((6-(4-(2-Aminoethyl)piperazin-1-yl)-3,5-dicyano-4-ethylpy ridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-(3-Aminopropyl)piperazin-1-yl)-3,5-dicyano-4-cyclop ropylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-((4-methylpiperazin-1-yl) methyl)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((6-(4-Acetylpiperazin-1-yl)-3,5-dicyano-4-ethylpyridin-2- yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(dimethylamino)pyridin-2-yl) thio)-2- phenylacetamide;

2-(4-Chlorophenyl)-2-((3,5-dicyano-6-(dimethylamino)-4-ethyl pyridin-2- yl)thio)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(2-hydroxyethyl)piperazin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-[(3,5-Dicyano-4-cyclopropyl-6-morpholino-2-pyridyl)sulfany l]-2-phenyl- acetamide;

2-((6-(4-Benzoylpiperazin-1-yl)-3,5-dicyano-4-ethylpyridin-2 -yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((5S,6S)-6-hydroxy-1-(methylsulfon yl)-1,8- diazaspiro[4.5]decan-8-yl)pyridin-2-yl)thio)-2-phenylacetami de;

2-((3,5-Dicyano-6-(4,4-difluoropiperidin-1-yl)-4-ethylpyridi n-2-yl)thio)-2- phenylacetamide;

(R)-2-((3,5-Dicyano-4-ethyl-6-((R)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide; 2-((3,5-dicyano-4-(furan-2-yl)-6-(4-methyl-1,4-diazepan-1-yl )pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-Amino-4-methylpiperidin-1-yl)-3,5-dicyano-4-ethylpy ridin-2-yl)thio)-2- phenylacetamide;

2-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)acetamide;

(2S)-2-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5 -dicyano-4- ethylpyridin-2-yl)piperidin-4-yl)propanamide;

2-((6-(4-(3-Aminooxetane-3-carbonyl)piperazin-1-yl)-3,5-dicy ano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

4-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)tetrahydro-2H-pyran-4-carboxamide;

2-((6-(4-(4-Aminotetrahydro-2H-pyran-4-carbonyl)piperazin-1- yl)-3,5-dicyano-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-(4-(2-hydroxyethyl)-1,4-diazepan-1-yl)-4-m ethoxypyridin-2- yl)thio)-2-phenylacetamide;

2-((6-(4-Aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-y l)thio)-2- phenylacetamide;

2-((6-((2-Aminoethyl)(methyl)amino)-3,5-dicyano-4-ethylpyrid in-2-yl)thio)-2- phenylacetamide;

2-((6-((2-Amino-2-oxoethyl)(methyl)amino)-3,5-dicyano-4-ethy lpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(3-hydroxyazetidin-1-yl)pyridin-2- yl)thio)-2- phenylacetamide;

2-(3,5-Dicyano-4-ethyl-6-((2-hydroxyethyl)(methyl)amino)pyri din-2-ylthio)-2- phenylacetamide;

2-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)-2-methylpropanamide;

2-((6-(4-(2-Aminoethoxy)piperidin-1-yl)-3,5-dicyano-4-ethylp yridin-2-yl)thio)-2- phenylacetamide; 1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)pyrrolidin- 3-yl dihydrogen phosphate;

2-((6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)ethyl dihydrogen phosphate;

1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)azetidin- 3-yl dihydrogen phosphate;

(2S)-2-((1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyan o-4-ethylpyridin-2- yl)piperidin-4-yl)oxy)ethyl 2-amino-3-methylbutanoate;

2-((1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-e thylpyridin-2- yl)piperidin-4-yl)oxy)ethyl dihydrogen phosphate;

1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)piperidin- 4-yl dihydrogen phosphate;

2-((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-(piperidin-4- yl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(propylsulfonyl)piperazin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(phenylsulfonyl)piperazin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((R)-3-hydroxypyrrolidin-1-yl)pyri din-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2-oxa-6-azaspiro[3.4]octan-6-yl)p yridin-2-yl)thio)-2- phenylacetamide;

(R)-2-((3,5-Dicyano-4-ethyl-6-(4-ethyl-1,4-diazepan-1-yl)pyr idin-2-yl)amino)-2- phenylacetamide;

(R)-2-((3,5-Dicyano-4-ethyl-6-(4-(3-(pyrrolidin-1-yl)propyl) -1,4-diazepan-1- yl)pyridin-2-yl)amino)-2-phenylacetamide;

2-(3,5-Dicyano-4-cyclopropyl-6-(3-hydroxypiperidin-1-yl)pyri din-2-ylthio)-2- phenylacetamide;

2-((3,5-Dichloro-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl) pyridin-2-yl)thio)-2- phenylacetamide; 2-((3,5-Dicyano-6-(1,1-dioxidothiomorpholino)-4-ethylpyridin -2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(methyl(2-(piperazin-1-yl)ethyl)am ino)pyridin-2-yl)thio)- 2-phenylacetamide;

(R)-2-((3,5-Dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-((2-(4-(Aminomethyl)-4-hydroxypiperidin-1-yl)ethyl)(me thyl)amino)-3,5- dicyano-4-ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((4-Cyano-3-(1,4-diazepan-1-yl)-6,7-dihydro-5H-cyclopenta[ c]pyridin-1-yl)thio)-2- phenylacetamide;

2-((6-(4-(1H-Imidazol-1-yl)piperidin-1-yl)-3,5-dicyano-4-eth ylpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(pyridin-4-ylmethyl)piperazin-1 -yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-6-(2-(dimethylamino)ethoxy)-4-ethylpyridin-2 -yl)thio)-2- phenylacetamide;

2-((1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-c yclopropylpyridin-2- yl)piperidin-3-yl)amino)acetic acid;

2-((3,5-Dicyano-4-ethyl-6-(4-(oxazol-2-ylmethyl)piperazin-1- yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-((1H-Pyrrol-2-yl) methyl) piperazin-1-yl)-3,5-dicyano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-(3,4-dihydro-2,7-naphthyridin-2 (1H)-yl)-4-ethylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl)pyri din-2-yl)thio)-2-(pyridin- 3-yl)acetamide;

2-((6-(4-((1H-Pyrrol-3-yl)methyl)piperazin-1-yl)-3,5-dicyano -4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(isoxazol-3-ylmethyl)piperazin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide; 2-((3,5-Dicyano-4-ethyl-6-(4-(oxazol-5-ylmethyl)piperazin-1- yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(isoxazol-4-ylmethyl)piperazin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

3-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)oxetane-3-carboxamide;

2-((6-(4-((1H-Pyrazol-4-yl)methyl)piperazin-1-yl)-3,5-dicyan o-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-(4-((1H-Imidazol-5-yl)methyl)piperazin-1-yl)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(1-hydroxy-2-methylpropan-2-yl) piperazin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((6-(4-((1H-Imidazol-2-yl)methyl)piperazin-1-yl)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-(dimethylamino)-4-methoxypyridin-2-yl)thio )-2-phenylacetamide; 2-((3,5-Dicyano-6-(dimethylamino)-4-ethoxypyridin-2-yl)thio) -2-phenylacetamide; 2-((3,5-Dicyano-4-ethoxy-6-(4-(2-hydroxyethyl)-1,4-diazepan- 1-yl) pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(2-hydroxy-2-methylpropyl)-1,4- diazepan-1-yl)pyridin- 2-yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(thiazol-5-ylmethyl)piperazin-1 -yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(piperazin-1-yl)pyridin-2-yl)thio) -2-(4- fluorophenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(isothiazol-4-ylmethyl)piperazi n-1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-(4- fluorophenyl)acetamide;

2-((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2- (5-fluoropyridin-2- yl)acetamide; 2-((3,5-Dicyano-4-ethyl-6-(4-(furan-3-ylmethyl)piperazin-1-y l)pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((2-morpholinoethyl)thio)pyridin-2 -yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-6-(4-methyl-1,4-diazepan-1-yl)-4-(methylthio )pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dichloro-4-ethyl-6-(4-(2-hydroxyethyl)-1,4-diazepan- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(hexahydropyrrolo[3,4-b][1,4]oxazi n-6(2H)-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(5- methylpyridin-2-yl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(6- fluoropyridin-2-yl)acetamide;

2-((3,5-Dicyano-6-(4-(dimethylamino)piperidin-1-yl)-4-ethylp yridin-2-yl)thio)-2-(4- fluorophenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl) pyridin-2-yl) thio)-2-(4- methylpyridin-2-yl) acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(3- methoxypyridin-2-yl)acetamide;

2-((3,5-Dicyano-6-(4-(dimethylamino)piperidin-1-yl)-4-ethylp yridin-2-yl)thio)-2-(2,4- difluorophenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1-yl )pyridin-2-yl)thio)-2-(5- fluoropyridin-2-yl)acetamide;

2-((3,5-Dicyano-4-ethoxy-6-(4-(2-hydroxyethyl)-1,4-diazepan- 1-yl)pyridin-2- yl)thio)propanamide;

2-((3,5-Dicyano-6-(4-(2-hydroxyethyl)-1,4-diazepan-1-yl)-4-p ropoxypyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(4- methoxypyridin-2-yl)acetamide; 2-((3,5-Dicyano-4-ethyl-6-(2-methyl-2,8-diazaspiro[4.5]decan -8-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-(4-(dimethylamino)piperidin-1-yl)-4-ethylp yridin-2-yl)thio)-2-(3,4- difluorophenyl)acetamide;

1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2- yl)piperidine-4-carboxamide;

2-((3,5-Dicyano-6-((2-(dimethylamino)ethyl)thio)-4-ethylpyri din-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-6-((3S,4R)-3,4-dihydroxypyrrolidin-1-yl)-4-e thylpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(3- fluoropyridin-2-yl) acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(5- methoxypyridin-2-yl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(1-hydroxy-2-methylpropan-2-yl) piperazin-1- yl)pyridin-2-yl)thio)-2-(4-fluorophenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(3- (trifluoromethyl)phenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(2-hydroxyethoxy)piperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl) pyridin-2-yl)thio)-2-(2- fluoropyridin-3-yl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl) pyridin-2-yl)thio)-2-(6- fluoropyridin-3-yl)acetamide;

3-((6-(2-Amino-2-oxo-1-phenylethylthio)-3,5-dicyano-4-ethylp yridin-2- yl)(methyl)amino)propanamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(oxetan-3-yloxy)piperidin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-6-(4-((2,2-difluoroethyl) amino)-4-methylpiperidin-1-yl)-4- ethylpyridin-2-yl) thio)-2-phenylacetamide; 2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(4- (trifluoromethyl)phenyl)acetamide;

2-((6-(4-Aminopiperazin-1-yl)-3,5-dicyano-4-ethylpyridin-2-y l)thio)-2- phenylacetamide;

2-((6-((2-Amino-2-oxoethyl)thio)-3,5-dicyano-4-ethylpyridin- 2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(pyrrolo[3,4-c]pyrazol-5(1H,4H,6H) -yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-(5-methoxypyridin-2- yl)acetamide;

2-((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-(5-methylpyridin-2- yl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(2- fluoropyridin-4-yl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-hydroxy-4-(hydroxymethyl)piperi din-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2-oxo-3-oxa-1,8-diazaspiro[4.5]de can-8-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((6-(4-Amino-4-(hydroxymethyl)piperidin-1-yl)-3,5-dicyano- 4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-(4-(Aminomethyl)-4-hydroxypiperidin-1-yl)-3,5-dicyano- 4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-(3-Benzoylphenyl)-2-((3,5-dicyano-4-ethyl-6-(4-(2-hydroxye thyl)-1,4-diazepan-1- yl)pyridin-2-yl)thio)acetamide;

2-(4-Benzoylphenyl)-2-((3,5-dicyano-4-ethyl-6-(4-(2-hydroxye thyl)-1,4-diazepan-1- yl)pyridin-2-yl)thio)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(2- methylpyridin-4-yl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(3- (pyrrolidin-1-yl)phenyl)acetamide; 2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(3- fluoropyridin-4-yl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(2,5- difluoropyridin-4-yl)acetamide;

2-((3,5-Dicyano-6-(4-(2,5-dioxoimidazolidin-1-yl)piperidin-1 -yl)-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

4-Amino-1-(6-((2-amino-2-oxo-1-phenylethyl) thio)-3, 5-dicyano-4-ethylpyridin-2-yl) piperidine-4-carboxamide;

2-((3,5-Dicyano-6-(4-(2,5-dioxopyrrolidin-1-yl)piperidin-1-y l)-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2- phenylacetamide (isomer 1);

2-((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2- phenylacetamide (Isomer 2) ;

2-((3,5-Dicyano-4-ethyl-6-(2-oxo-1-oxa-3,8-diazaspiro[4.5]de can-8-yl)pyridin-2- yl)thio)-2-phenylacetamide;

1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)-4- hydroxy piperidine-4-carboxamide;

1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)azetidin- 3-yl carbamate;

2-((3,5-Dicyano-6-(4-(2,4-dioxooxazolidin-3-yl)piperidin-1-y l)-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

3-((6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-2-hydroxy-2-methylpropanamide;

2-((3,5-Dicyano-4-ethyl-6-(3-(hydroxymethyl)azetidin-1-yl)py ridin-2-yl)thio)-2- phenylacetamide;

2-(3,5-Dicyano-4-ethyl-6-(piperazin-1-yl)pyridin-2-ylthio)-2 -(thiophen-3- yl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl) pyridin-2-yl) thio)-2-(5- methylpyridin-3-yl) acetamide; 2-((6-(4-(3-Amino-2-oxopyrrolidin-1-yl)piperidin-1-yl)-3,5-d icyano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)piperidin- 4-yl (2S)-2-amino-3-methylbutanoate;

2-((6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2-yl) (methyl) amino)ethyl (2S)-2-amino-3-methylbutanoate;

2,2'-((3,5-Dicyano-4-ethylpyridine-2,6-diyl)bis(sulfanediyl) )bis(2-phenylacetamide) ;

(2S)-(1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4 –ethyl pyridin-2- yl)azetidin-3-yl)methyl 2-amino-3-methylbutanoate;

2-((6-(3-Aminoazetidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-yl )thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-methylpyridin-2-yl)thio)-2-phenyla cetamide;

N-(1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-et hylpyridin-2- yl)piperidin-4-yl)-2-hydroxyacetamide;

N-(1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-et hylpyridin-2- yl)azetidin-3-yl)-2-hydroxyacetamide;

2-((3-Cyano-4-ethyl-5-methyl-6-(piperazin-1-yl)pyridin-2-yl) thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(5-methyl-2,5-diazabicyclo[2.2.1]h eptan-2-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(2-(pyrrolidin-1-yl)ethyl)piper azin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-phenylacetamide-2- d;

(R)-2-((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)th io)-2- phenylacetamide-2-d;

2-((6-(4-(4-Bromobenzoyl)piperazin-1-yl)-3,5-dicyano-4-ethyl pyridin-2-yl)thio)-2- phenylacetamide; 2-((3,5-Dicyano-4-ethyl-6-(4-(2-hydroxyethyl)-1,4-diazepan-1 -yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-6-(4-cyanopiperidin-1-yl)-4-ethylpyridin-2-y l)thio)-2- phenylacetamide;

(S)-2-((3,5-Dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-Amino-4-methylpiperidin-1-yl)-3,5-dicyano-4-cyclopr opylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl)pyri din-2-yl)thio)-2-(pyridin- 2-yl)acetamide;

2-((3,5-Dichloro-4-ethyl-6-(piperazin-1-yl)pyridin-2-yl)thio )-2-phenylacetamide; tert-Butyl (1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)piperidin-4-yl)carbamate;

2-((6-(3-(2-Amino-2-oxoethyl)azetidin-1-yl)-3,5-dicyano-4-et hylpyridin-2-yl)thio)-2- phenylacetamide;

(2R)-1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4- ethylpyridin-2- yl)azetidin-3-yl 2-amino-3-methylbutanoate;

2-((3,5-Dicyano-4-ethyl-6-(methyl((5-oxo-4,5-dihydro-1H-1,2, 4-triazol-3- yl)methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-((6-(((4H-1,2,4-Triazol-3-yl)methyl)(methyl)amino)-3,5-dic yano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethoxy-6-methylpyridin-2-yl)thio)-2-phenyl acetamide;

2-((3,5-Dicyano-4,6-diethylpyridin-2-yl)thio)-2-phenylacetam ide;

2-((6-((2-(4H-1,2,4-Triazol-4-yl)ethyl)(methyl)amino)-3,5 -dicyano-4-ethylpyridin-2-yl)thio)- 2- phenylacetamide;

2-((6-(((1H-Pyrazol-3-yl)methyl)(methyl)amino)-3,5-dicyano-4 -ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-(6,7-dihydro-1H-[1,2,3]triazolo[4,5-c]pyri din-5(4H)-yl)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide; 2-((6-(((1H-Imidazol-2-yl)methyl)(methyl)amino)-3,5-dicyano- 4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-(((1H-Imidazol-5-yl)methyl)(methyl)amino)-3,5-dicyano- 4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

(2R)-2-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5 -dicyano-4- ethylpyridin-2-yl)piperidin-4-yl)propanamide;

4-(2-Amino-1-((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan- 1-yl)pyridin-2- yl)thio)-2-oxoethyl)benzamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-hydroxypyrrolidin-1-yl)py ridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(3-hydroxypyrrolidin-1-yl)pyridin- 2-yl)thio)-2- phenylacetamide;

(2R)-2-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5 -dicyano-4- cyclopropyl pyridin-2-yl)piperidin-4-yl)propanamide;

2-((6-((2-Aminoethyl)(methyl)amino)-3,5-dicyano-4-cyclopropy lpyridin-2-yl)thio)-2- phenylacetamide;

2-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl) thio)-3,5-dicyano-4- cyclopropylpyridin-2-yl)piperidin-4-yl)-2-methylpropanamide;

4-(2-Amino-1-((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin- 2-yl)thio)-2- oxoethyl)benzamide;

2-(6-(4-Aminopiperidin-1-yl)-3-cyano-4-ethyl-5-methylpyridin -2-ylthio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2-(4-(N- methylsulfamoyl)phenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(6-fluoro-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2- phenylacetamide;

2-((6-(4-Amino-3,3-difluoropiperidin-1-yl)-3,5-dicyano-4-eth ylpyridin-2-yl)thio)-2- phenylacetamide;

tert-Butyl (1-(6-((2-amino-2-oxo-1-phenylethyl) thio)-3,5-dicyano-4-ethylpyridin-2- yl)-3,3-difluoropiperidin-4-yl) carbamate; 2-((3,5-Dicyano-4-cyclopropyl-6-((2-hydroxyethyl)(methyl)ami no)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-hydroxyazetidin-1-yl)pyri din-2-yl)thio)-2- phenylacetamide;

1-(6-((2-Amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2- yl)pyrrolidine-3-carboxamide;

2-((6-((3-Aminopropyl) (methyl) amino)-3, 5-dicyano-4-cyclopropylpyridin-2-yl) thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-((2-(3-hydroxyazetidin-1-yl) -2- oxoethyl)(methyl)amino) pyridin-2-yl)thio)-2-phenylacetamide;

2-((6-(4-((2-Amino-2-oxoethyl)amino)piperidin-1-yl)-3,5-dicy ano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-((2-Amino-2-oxoethyl)(methyl)amino)-3,5-dicyano-4-cycl opropylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-((2-Amino-2-oxo-1-phenylethyl) thio)-3, 5-dicyano-4-cyclopropylpyridin-2- yl)(methyl)amino)ethyl carbamate;

(2R)-2-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5 -dicyano-4- ethylpyridin-2-yl)piperidin-4-yl)-3-hydroxypropanamide;

(2S)-2-Amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl) thio)-3, 5-dicyano-4- ethylpyridin-2-yl) piperidin-4-yl)-3-hydroxypropanamide;

2-(4-(2-Amino-2-oxoethyl)phenyl)-2-(3,5-dicyano-4-ethyl-6-(4 -methyl-1,4- diazepan-1-yl)pyridin-2-ylthio)acetamide;

2-(4-(2-Amino-2-oxoethyl)phenyl)-2-(3,5-dicyano-6-(dimethyla mino)-4-ethylpyridin- 2-ylthio)acetamide;

2-((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-(4-(N- methylsulfamoyl)phenyl)acetamide;

2-((3,5-Dicyano-6-(dimethylamino-d 6 )-4-ethylpyridin-2-yl)thio)-2-phenylacetamide; (R)-2-((3,5-Dicyano-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin- 1-yl)pyridin-2-yl)thio)-2- phenylacetamide; (R)-2-((3,5-Dicyano-6-(4-(dimethylamino)piperidin-1-yl)-4-et hylpyridin-2-yl)thio)-2- phenylacetamide;

2-(3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-ylthio)-2- (3-(2- (dimethylamino)ethoxy)phenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(neopentylamino)piperidin-1-yl) pyridin-2-yl)thio)-2-(4- fluorophenyl)acetamide;

2-((3,5-dicyano-4-ethyl-6-(3-fluoro-4-A(neopentylamino)piper idin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-y l)thio)-2-(4- (trifluoromethyl)phenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide;

(R)-2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin -2-yl)thio)-2- phenylacetamide;

2-((6-((2-amino-2-oxoethyl)(methyl)amino)-3,5-dicyano-4-ethy lpyridin-2-yl)thio)-2- phenylacetamide; (single enantiomer)

(3S)-1-(6-((2-amino-2-oxo-1-phenylethyl) thio)-3, 5-dicyano-4-ethylpyridin-2-yl) Pyrrolidin-3-yl dihydrogen phosphate;

(3R)-1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4- ethylpyridin-2- yl)pyrrolidin-3-yl dihydrogen phosphate;

(S)-1-(6-(((S)-2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano -4-ethylpyridin-2- yl)pyrrolidin-3-yl dihydrogen phosphate;

(S)-1-(6-(((R)-2-amino-2-oxo-1-phenylethyl) thio)-3,5-dicyano-4-ethylpyridin-2-yl) pyrrolidin-3-yl dihydrogen phosphate;

2-((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio)- 2-(3- (dimethylphosphoryl)phenyl)acetamide;

2-((3,5-Dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl)pyri din-2-yl)thio)-2-(3-( dimethylphosphoryl)phenyl)acetamide;

(R)-2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4- ethylpyridin-2- yl)(methyl)amino)ethyl dihydrogen phosphate; (R)-2-((3,5-dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl)thio)-2-(4- methoxyphenyl)acetamide;

(R)-2-(4-chlorophenyl)-2-((3,5-dicyano-4-ethyl-6-((S)-3-hydr oxypyrrolidin-1- yl)pyridin-2-yl)thio)acetamide;

(R)-2-((3,5-dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl)thio)-2-(4- fluoro phenyl)acetamide;

(S)-1-(6-(((R)-2-amino-1-(4-fluorophenyl)-2-oxoethyl)thio)-3 ,5-dicyano-4- ethylpyridin-2-yl)pyrrolidin-3-yl dihydrogen phosphate;

2-((3, 5-dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl) thio)-2-(4- fluorophenyl) acetamide;

2-((3,5-dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl) thio)-2-(2, 6- difluorophenyl) acetamide;

2-((3, 5-dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl) thio)-2-(2, 3- difluorophenyl) acetamide;

2-((3, 5-dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl) thio)-2-(2, 4- difluorophenyl) acetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((S)-2-(hydroxymethyl)pyrrolidi n-1-yl)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((2-hydroxyethyl)(methyl)amino) piperidin-1-yl)pyridin- 2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((2-hydroxy-2-methylpropyl)(met hyl)amino)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(pyrrolidin-1-ylmethyl)piperidi n-1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((2-methoxy-2-methylpropyl)amin o)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((2-hydroxy-2-methylpropyl)amin o)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(4-(cyclobutylamino)piperidin-1-yl)-4-ethy lpyridin-2-yl)thio)-2- phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-(4-(((3-methyloxetan-3-yl)methyl)a mino)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(4-methylpiperazin-1-yl)piperid in-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((R)-2-methylpyrrolidin-1-yl)pi peridin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(4-((2R,5S)-2,5-dimethylpyrrolidin-1-yl)pi peridin-1-yl)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((S)-2-methylpyrrolidin-1-yl)pi peridin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(4-(cyclobutyl(methyl)amino)piperidin-1-yl )-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-(6-(4-(benzylamino)piperidin-1-yl)-3,5-dicyano-4-ethylpyri din-2-ylthio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(((6-methoxypyridin-2-yl)methyl )amino)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((S)-3-fluoropyrrolidin-1-yl)pi peridin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(methyl(2-((R)-2-methylpyrrolidin- 1- yl)ethyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((R)-3-fluoropyrrolidin-1-yl)pi peridin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(4-((2S,5S)-2,5-dimethylpyrrolidin-1-yl)pi peridin-1-yl)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(methyl(2-((S)-2-methylpyrrolidin- 1- yl)ethyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((R)-2-(hydroxymethyl)pyrrolidi n-1-yl)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(4-(dimethylamino)piperidin-1-yl)-4-ethylp yridin-2-yl)thio)-2-(4- fluorophenyl)acetamide; 2-((3,5-dicyano-4-ethyl-6-(4-(((1-methylcyclobutyl)methyl)am ino)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(((6-methoxypyridin-3-yl)methyl )amino)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-(3,5-dicyano-4-ethyl-6-((2-(ethylamino)ethyl)(methyl)amino )pyridin-2-ylthio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((4-methylpiperazin-1-yl)methyl )piperidin-1-yl)pyridin- 2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(methyl(2-(methylamino)ethyl)amino )pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-6-(4-((2R,5R)-2,5-dimethylpyrrolidin-1-yl)pi peridin-1-yl)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(((1-methylcyclopropyl)methyl)a mino)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((4-fluorobenzyl)amino)piperidi n-1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((S)-2-(hydroxymethyl)pyrrolid in-1- yl)ethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-(3,5-dicyano-6-((2-((2S,5R)-2,5-dimethylpyrrolidin-1-yl)et hyl)(methyl)amino)-4- ethylpyridin-2-ylthio)-2-phenylacetamide;

2-((6-((2-(azepan-1-yl)ethyl)(methyl)amino)-3,5-dicyano-4-et hylpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(methyl(2-(piperidin-1-yl)ethyl)am ino)pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((R)-2-(hydroxymethyl)pyrrolid in-1- yl)ethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-(3,5-dicyano-4-ethyl-6-((2-(ethyl(methyl)amino)ethyl)(meth yl)amino)pyridin-2- ylthio)-2-phenylacetamide;

2-((3,5-dicyano-6-((2-((2R,5R)-2,5-dimethylpyrrolidin-1-yl)e thyl)(methyl)amino)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide; 2-(3,5-dicyano-4-ethyl-6-((2-((S)-3-hydroxypyrrolidin-1- yl)ethyl)(methyl)amino)pyridin-2-ylthio)-2-phenylacetamide;

methyl 2-((1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-e thylpyridin-2- yl)piperidin-4-yl)amino)-2-methylpropanoate;

2-((3,5-dicyano-4-ethyl-6-(methyl(2-(neopentylamino)ethyl)am ino)pyridin-2- yl)thio)-2-phenylacetamide;

2-(3,5-dicyano-4-ethyl-6-(methyl(2-(1-methylcyclopropylamino )ethyl)amino)pyridin- 2-ylthio)-2-phenylacetamide;

2-((3,5-dicyano-6-((2-((2S,5S)-2,5-dimethylpyrrolidin-1-yl)e thyl)(methyl)amino)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((2-methoxyethyl)amino)ethyl)( methyl)amino)pyridin- 2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((2-methoxy-2-methylpropyl)(met hyl)amino)piperidin- 1-yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-((2-(dimethylamino)ethyl)(methyl)amino)-4- ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-(3,5-dicyano-4-ethyl-6-((2-((R)-3-hydroxypyrrolidin-1- yl)ethyl)(methyl)amino)pyridin-2-ylthio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((2-fluoroethyl)amino)ethyl)(m ethyl)amino)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(4-(3,3-difluoropyrrolidin-1-yl)piperidin- 1-yl)-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-e thylpyridin-2- yl)piperidin-4-yl)amino)acetic acid;

2-((6-((3-aminocyclobutyl)(methyl)amino)-3,5-dicyano-4-ethyl pyridin-2-yl)thio)-2- phenylacetamide;

(R)-2-(3,5-dicyano-4-ethyl-6-(methyl((R)-tetrahydrofuran-3-y l)amino)pyridin-2- ylthio)-2-phenylacetamide;

(S)-2-(3,5-dicyano-4-ethyl-6-(methyl((R)-tetrahydrofuran-3-y l)amino)pyridin-2- ylthio)-2-phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-(4-morpholinopiperidin-1-yl)pyridi n-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(2-hydroxyethyl)-3-oxopiperazin -1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1-yl )pyridin-2-yl)thio)-2-(4- fluorophenyl)acetamide;

(R)-2-((6-((3S,4R)-4-amino-3-fluoropiperidin-1-yl)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(3-fluoro-4-(methylamino)piperidin -1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

rel-2-((6-(trans)-4-amino-3-fluoropiperidin-1-yl)-3,5-dicyan o-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

(R)-2-((6-((3R,4S)-4-amino-3-fluoropiperidin-1-yl)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(3-fluoro-4-((2-methoxyethyl)amino )piperidin-1-yl)pyridin- 2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(methyl(2-(pyrrolidin-1-yl)ethyl)a mino)pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-6-(3-((dimethylamino)methyl)pyrrolidin-1-yl) -4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((2-hydroxy-2-methylpropyl)amin o)piperidin-1- yl)pyridin-2-yl)thio)-2-(4-fluorophenyl)acetamide;

(R)-2-((6-((3S,4R)-4-amino-3-hydroxypiperidin-1-yl)-3,5-dicy ano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-((2-(diethylamino)ethyl)(methyl)amino)-4-e thylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-6-((2-((R)-3-(dimethylamino)pyrrolidin-1-yl) ethyl)(methyl)amino)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-((2-((S)-3-(dimethylamino)pyrrolidin-1-yl) ethyl)(methyl)amino)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide; (R)-2-((6-((3R,4R)-4-amino-3-fluoropiperidin-1-yl)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

(R)-2-((6-((3S,4S)-4-amino-3-fluoropiperidin-1-yl)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(3-(methylamino)pyrrolidin-1-yl)py ridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-y l)thio)-2-(4- fluorophenyl)acetamide;

(R)-2-((6-((3R,4R)-4-amino-3-hydroxypiperidin-1-yl)-3,5-dicy ano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-((R)-3-aminopyrrolidin-1-yl)-3,5-dicyano-4-ethylpyridi n-2-yl)thio)-2- phenylacetamide;

2-((6-(3-(aminomethyl)pyrrolidin-1-yl)-3,5-dicyano-4-ethylpy ridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(methylamino)piperidin-1-yl)pyr idin-2-yl)thio)-2-(4- fluorophenyl)acetamide;

2-((3,5-dicyano-6-(4-(cyclopropylamino)-3-fluoropiperidin-1- yl)-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-((S)-3-aminopyrrolidin-1-yl)-3,5-dicyano-4-ethylpyridi n-2-yl)thio)-2- phenylacetamide;

2-((6-((2-((R)-3-aminopyrrolidin-1-yl)ethyl)(methyl)amino)-3 ,5-dicyano-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

3,5-dicyano-6-((R)-3-(dimethylamino)pyrrolidin-1-yl)-4-ethyl pyridin-2-yl)thio)-2-(4- fluorophenyl)acetamide;

(S)-2-((6-((3S,4R)-4-amino-3-fluoropiperidin-1-yl)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(neopentylamino)piperidin-1-yl) pyridin-2-yl)thio)-2-(4- (trifluoromethyl)phenyl)acetamide;

tert-butyl ((3S,4R)-1-(6-(((R)-2-amino-2-oxo-1-phenylethyl)thio)-3,5-di cyano-4- ethylpyridin-2-yl)-3-hydroxypiperidin-4-yl)carbamate; rel-tert-butyl (cis)-1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4 - ethylpyridin-2-yl)-3-fluoropiperidin-4-yl)carbamate;

2-((6-((2-((S)-3-aminopyrrolidin-1-yl)ethyl)(methyl)amino)-3 ,5-dicyano-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-((R)-3-(dimethylamino)pyrrolidin-1-yl)-4-e thylpyridin-2-yl)thio)-2- phenylacetamide;

tert-butyl ((3R,4S)-1-(6-(((R)-2-amino-2-oxo-1-phenylethyl)thio)-3,5-di cyano-4- ethylpyridin-2-yl)-3-hydroxypiperidin-4-yl)carbamate;

rel-tert-butyl (cis)-1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4 - ethylpyridin-2-yl)-3-fluoropiperidin-4-yl)carbamate;

2-((3,5-dicyano-6-((S)-3-(dimethylamino)pyrrolidin-1-yl)-4-e thylpyridin-2-yl)thio)-2- phenylacetamide;

(S)-2-((6-((3R,4S)-4-amino-3-fluoropiperidin-1-yl)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((S)-3-((2-hydroxy-2-methylpropyl) amino)pyrrolidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

tert-butyl ((3R,4R)-1-(6-(((R)-2-amino-2-oxo-1-phenylethyl)thio)-3,5-di cyano-4- ethylpyridin-2-yl)-3-hydroxypiperidin-4-yl)carbamate;

2-((3,5-dicyano-6-((S)-3-(dimethylamino)pyrrolidin-1-yl)-4-e thylpyridin-2-yl)thio)-2- (4-fluorophenyl)acetamide;

rel-2-((6-cis-4-amino-3-fluoropiperidin-1-yl)-3,5-dicyano-4- ethylpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(methylamino)piperidin-1-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-6-(4-(dimethylamino)piperidin-1-yl)-4-ethylp yridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(ethyl(methyl)amino)piperidin-1 -yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(neopentylamino)piperidin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-(4-(methyl(neopentyl)amino)piperid in-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(4-(cyclopropylamino)piperidin-1-yl)-4-eth ylpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((2-methoxyethyl)amino)piperidi n-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(4-((2,2-difluoroethyl)amino)piperidin-1-y l)-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((R)-2-((neopentylamino)methyl)mor pholino)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(2-((dimethylamino)methyl)morpholino)-4-et hylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-6-(2-((diethylamino)methyl)morpholino)-4-eth ylpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(2-(pyrrolidin-1-ylmethyl)morpholi no)pyridin-2-yl)thio)-2- phenylacetamide;

(R)-2-((6-((R)-2-(aminomethyl)morpholino)-3,5-dicyano-4-ethy lpyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(2-(aminomethyl)morpholino)-3,5-dicyano-4-ethylpyridin -2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(2-((methylamino)methyl)morpholino )pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-((R)-2-(aminomethyl)morpholino)-3,5-dicyano-4-ethylpyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-6-(3-((dimethylamino)methyl)piperidin-1-yl)- 4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(3-((methylamino)methyl)piperidin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((S)-2-((neopentylamino)methyl)mor pholino)pyridin-2- yl)thio)-2-phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-((S)-3-((neopentylamino)methyl)pip eridin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-amino-N-(((2S)-4-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3, 5-dicyano-4- ethylpyridin-2-yl)morpholin-2-yl)methyl)-2-methylpropanamide ;

2-((6-((S)-3-(aminomethyl)piperidin-1-yl)-3,5-dicyano-4-ethy lpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-6-((R)-2-((diethylamino)methyl)morpholino)-4 -ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-amino-N-(((2R)-4-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3, 5-dicyano-4- ethylpyridin-2-yl)morpholin-2-yl)methyl)-2-methylpropanamide ;

2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-y l)thio)-2-(3- fluoropyridin-2-yl)acetamide;

2-((6-((S)-2-(aminomethyl)morpholino)-3,5-dicyano-4-ethylpyr idin-2-yl)thio)-2- phenylacetamide;

2-amino-N-(((3S)-1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3, 5-dicyano-4- ethylpyridin-2-yl)piperidin-3-yl)methyl)-2-methylpropanamide ;

2-amino-N-(((3S)-1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3, 5-dicyano-4- ethylpyridin-2-yl)piperidin-3-yl)methyl)acetamide;

2-amino-N-(((2R)-4-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3, 5-dicyano-4- ethylpyridin-2-yl)morpholin-2-yl)methyl)acetamide;

2-((6-((R)-3-(aminomethyl)piperidin-1-yl)-3,5-dicyano-4-ethy lpyridin-2-yl)thio)-2-(4- fluorophenyl)acetamide;

2-((3,5-dicyano-4-ethyl-6-((R)-3-((neopentylamino)methyl)pip eridin-1-yl)pyridin-2- yl)thio)-2-(4-fluorophenyl)acetamide;

2-amino-N-(((2S)-4-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3, 5-dicyano-4- ethylpyridin-2-yl)morpholin-2-yl)methyl)acetamide;

N-(((R)-4-(6-(((R)-2-amino-2-oxo-1-phenylethyl)thio)-3,5-dic yano-4-ethylpyridin-2- yl)morpholin-2-yl)methyl)-2-hydroxyacetamide;

(S)-2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin -2-yl)thio)-2- phenylacetamide; 2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-(2-hydroxyethyl)-N-methylacetamide;

2-((3,5-dicyano-4-ethyl-6-((S)-3-(methylamino)piperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-amino-4-methylpiperidin-1-yl)-3,5-dicyano-4-ethylpy ridin-2-yl)thio)-2- phenylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-((1-(hydroxymethyl)cyclopropyl)methyl)-N -methylacetamide;

2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4- cyclopropylpyridin-2-yl)azetidin-3-yl)acetamide;

(2S)-2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5 -dicyano-4- cyclopropylpyridin-2-yl)azetidin-3-yl)-3-hydroxypropanamide;

2-((6-((S)-3-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin -2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((R)-3-hydroxypyrrolidin-1-yl) -2- oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

(2R)-2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5 -dicyano-4- cyclopropylpyridin-2-yl)azetidin-3-yl)-3-hydroxypropanamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-(3-hydroxy-2,2-dimethylpropyl)-N-methyla cetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((S)-3-hydroxypyrrolidin-1-yl) -2- oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-((6-(4-amino-4-methylpiperidin-1-yl)-3,5-dicyano-4-ethylpy ridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-(aminomethyl)-4-fluoropiperidin-1-yl)-3,5-dicyano-4 -ethylpyridin-2-yl)thio)- 2-phenylacetamide hydrochloride;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-cycl opropylpyridin-2- yl)(methyl)amino)-N-(2-aminoethyl)acetamide hydrochloride;

2-((3,5-dicyano-4-ethyl-6-(methyl(2-oxo-2-(pyrrolidin-1-yl)e thyl)amino)pyridin-2- yl)thio)-2-phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-((2-(4-hydroxypiperidin-1-yl)-2- oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(methyl(2-oxo-2-(piperazin-1-yl)et hyl)amino)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(methyl(2-morpholino-2-oxoethyl)am ino)pyridin-2- yl)thio)-2-phenylacetamide;

(R)-2-((6-((S)-3-(aminomethyl)-3-hydroxypyrrolidin-1-yl)-3,5 -dicyano-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((S)-3-(guanidinooxy)pyrrolidin-1- yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-amino-N-(2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dic yano-4-ethylpyridin-2- yl)(methyl)amino)ethyl)-2-methylpropanamide;

2-((6-((2-(2-aminoethoxy)ethyl)(methyl)amino)-3,5-dicyano-4- ethylpyridin-2- yl)thio)-2-phenylacetamide;

4-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)butanamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-(2-aminoethyl)acetamide;

2-((6-((2-(azetidin-1-yl)-2-oxoethyl)(methyl)amino)-3,5-dicy ano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-((R)-3-(aminomethyl)-3-fluoropyrrolidin-1-yl)-3,5-dicy ano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-(3-hydroxyazetidin-1-yl)-2- oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(guanidinooxy)piperidin-1-yl)py ridin-2-yl)thio)-2- phenylacetamide;

2-((6-(3-aminoazetidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-yl )thio)-2- phenylacetamide; (single stereoisomer)

2-((3,5-dicyano-4-ethyl-6-((R)-3-(methylamino)piperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-((2-((3R,4S)-3-hydroxy-4-(hydroxym ethyl)pyrrolidin-1-yl)- 2-oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamid e;

(R)-2-((6-((S)-3-(aminomethyl)-3-fluoropyrrolidin-1-yl)-3,5- dicyano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-cycl opropylpyridin-2- yl)(methyl)amino)-N-(1,3-dihydroxypropan-2-yl)acetamide;

2-((3,5-dicyano-4-ethyl-6-((S)-3-(oxetan-3-ylamino)piperidin -1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-cycl opropylpyridin-2- yl)(methyl)amino)-N,N-bis(2-hydroxyethyl)acetamide;

2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4- cyclopropylpyridin-2-yl)piperidin-4-yl)acetamide;

2-((3,5-dicyano-4-ethyl-6-(4-((2-hydroxyethyl)amino)-4-methy lpiperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-(guanidinooxy)ethyl)(methyl)am ino)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((6-(4-((2-aminoethyl)amino)piperidin-1-yl)-3,5-dicyano-4- ethylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((S)-2-(hydroxymethyl)morpholi no)-2- oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-((2-((cis)-3,4-dihydroxypyrrolidin-1-yl)-2 - oxoethyl)(methyl)amino)-4-ethylpyridin-2-yl)thio)-2-phenylac etamide;

2-((3,5-dicyano-4-ethyl-6-((2-((S)-3-(hydroxymethyl)pyrrolid in-1-yl)-2- oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((3S,4S)-3-hydroxy-4-(hydroxym ethyl)pyrrolidin-1-yl)- 2-oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamid e;

2-((3,5-dicyano-4-ethyl-6-((S)-3-(neopentylamino)piperidin-1 -yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((R)-3-(hydroxymethyl)pyrrolid in-1-yl)-2- oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide; 2-((3,5-dicyano-6-((2-((3R,4R)-3,4-dihydroxypyrrolidin-1-yl) -2- oxoethyl)(methyl)amino)-4-ethylpyridin-2-yl)thio)-2-phenylac etamide;

(R)-2-((3,5-dicyano-4-ethyl-6-((S)-3-hydroxy-3-(hydroxymethy l)pyrrolidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

(2S)-2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5 -dicyano-4- cyclopropylpyridin-2-yl)piperidin-4-yl)propanamide;

2-((6-(4-(2-aminoethoxy)piperidin-1-yl)-3,5-dicyano-4-cyclop ropylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(4-((2-hydroxyethyl)amino)pi peridin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-(1,3-dihydroxypropan-2-yl)acetamide;

2-((3,5-dicyano-6-((2-((3R,5S)-3,5-dihydroxypiperidin-1-yl)- 2- oxoethyl)(methyl)amino)-4-ethylpyridin-2-yl)thio)-2-phenylac etamide;

2-((3,5-dicyano-6-((2-((3S,4S)-3,4-dihydroxypyrrolidin-1-yl) -2- oxoethyl)(methyl)amino)-4-ethylpyridin-2-yl)thio)-2-phenylac etamide;

2-((3,5-dicyano-4-ethyl-6-(4-((2-hydroxyethyl)amino)-4-(hydr oxymethyl)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((R)-2-(hydroxymethyl)morpholi no)-2- oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-methoxyacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-((3R,4R)-3-hydroxy-4-(hydroxym ethyl)pyrrolidin-1-yl)- 2-oxoethyl)(methyl)amino)pyridin-2-yl)thio)-2-phenylacetamid e;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-(3-hydroxypropyl)-N-methylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-((R)-2,3-dihydroxypropyl)acetamide;

2-((6-(4-((2-amino-2-oxoethyl)amino)piperidin-1-yl)-3,5-dicy ano-4- cyclopropylpyridin-2-yl)thio)-2-phenylacetamide; 2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N,N-bis(2-hydroxyethyl)acetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-(2-hydroxyethyl)acetamide;

2-((6-((3-aminopropyl)(methyl)amino)-3,5-dicyano-4-ethylpyri din-2-yl)thio)-2- phenylacetamide;

2-((6-(3-(aminomethyl)azetidin-1-yl)-3,5-dicyano-4-ethylpyri din-2-yl)thio)-2- phenylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-((1-(hydroxymethyl)cyclopropyl)methyl)ac etamide;

(R)-2-((3,5-dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl)thio)-2-(2,4- difluorophenyl)acetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-(3-(hydroxymethyl)oxetan-3-yl)acetamide;

2-((3,5-dicyano-4-ethyl-6-(3-(guanidinooxy)azetidin-1-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-(3-hydroxypropyl)acetamide;

2-((3,5-dicyano-6-(4-(2,3-dihydroxypropyl)-1,4-diazepan-1-yl )-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-hydroxyacetamide;

3-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4- cyclopropylpyridin-2-yl)azetidin-3-yl)oxetane-3-carboxamide;

2-((3,5-dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl)pyri din-2-yl)thio)-2-(2- fluorophenyl)acetamide;

2-((3,5-dicyano-6-((S)-3-(cyclopropylamino)piperidin-1-yl)-4 -ethylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)-N-(3-hydroxy-2,2-dimethylpropyl)acetamide; N-(2-(4H-1,2,4-triazol-4-yl)ethyl)-2-((6-((2-amino-2-oxo-1-p henylethyl)thio)-3,5- dicyano-4-ethylpyridin-2-yl)(methyl)amino)acetamide;

N1-(2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4- ethylpyridin-2- yl)(methyl)amino)ethyl)oxalamide;

2-((6-(3-(aminomethyl)-3-fluoroazetidin-1-yl)-3,5-dicyano-4- ethylpyridin-2-yl)thio)- 2-phenylacetamide;

(R)-2-((3,5-dicyano-4-ethyl-6-((R)-3-hydroxy-3-(hydroxymethy l)pyrrolidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-((S)-3-((2,2-difluoroethyl)amino)piperidin -1-yl)-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((6-((R)-3-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin -2-yl)thio)-2- phenylacetamide;

2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-methoxypyridin-2 -yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((S)-4-hydroxyisoxazolidin-2-yl)py ridin-2-yl)thio)-2- phenylacetamide;

(R)-2-((3,5-dicyano-4-ethyl-6-((3-hydroxypropyl)(methyl)amin o)pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-6-((S)-3-hydroxypyrrolidin-1-yl)-4-methoxypy ridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(3-methoxyazetidin-1-yl)piperid in-1-yl)pyridin-2- yl)thio)-2-phenylacetamide; and

2-((3,5-dicyano-4-ethyl-6-(4-(3-methoxyazetidin-1-yl)piperid in-1-yl)pyridin-2- yl)thio)-2-(4-fluorophenyl)acetamide; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably, presently invented novel compounds of Formula (IVbbr) are selected from: 2-{[3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl]sulfan yl}-2-phenylacetamide; 2-((6-((2-Amino-2-oxoethyl)(methyl)amino)-3,5-dicyano-4-ethy lpyridin-2-yl)thio)-2- phenylacetamide;

(R)-2-((3,5-Dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-Aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-y l)thio)-2- phenylacetamide;

2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-y l)thio)-2-(4- fluorophenyl)acetamide;

2-((3,5-dicyano-6-(4-(cyclobutyl(methyl)amino)piperidin-1-yl )-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(3-fluoro-4-A(neopentylamino)piper idin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

(R)-2-((3,5-dicyano-4-ethyl-6-((2-hydroxyethyl)(methyl)amino )pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-6-(4-(cyclobutyl(methyl)amino)piperidin-1-yl )-4-ethylpyridin-2- yl)thio)-2-(4-fluorophenyl)acetamide; and

2-((3,5-dicyano-4-ethyl-6-(methyl(1-methylpyrrolidin-3-yl)am ino)pyridin-2-yl)thio)- 2-phenylacetamide;

or a pharmaceutically acceptable salt or prodrug thereof. Suitably, presently invented novel compounds of Formula (IVbbr) are selected from: (R)-2-((3,5-dicyano-4-ethyl-6-((2-hydroxyethyl)(methyl)amino )pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-6-(4-(cyclobutyl(methyl)amino)piperidin-1-yl )-4-ethylpyridin-2- yl)thio)-2-(4-fluorophenyl)acetamide; and

2-((3,5-dicyano-4-ethyl-6-(methyl(1-methylpyrrolidin-3-yl)am ino)pyridin-2-yl)thio)- 2-phenylacetamide; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably, presently invented novel compounds of Formula (Vbbr) are selected from: 2-((3,5-dicyano-4-cyclopropyl-6-(1,4-diazepan-1-yl)pyridin-2 -yl)thio)-2- phenylacetamide;

2-{[3,5-dicyano-4-cyclopropyl-6-(4-ethyl-1,4-diazepan-1-yl)p yridin-2-yl]sulfanyl}-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-propyl-1,4-diazepan-1-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-{[3,5-dicyano-4-ethyl-6-(4-ethyl-1,4-diazepan-1-yl)pyridin -2-yl]sulfanyl}-2- phenylacetamide;

2-{[3,5-dicyano-4-ethyl-6-(5-oxo-1,4-diazepan-1-yl)pyridin-2 -yl]sulfanyl}-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-morpholinopyridin-2-yl)thio) -2-(pyridin-4- yl)acetamide;

2-{[3,5-dicyano-4-ethyl-6-(4-methyl-3-oxopiperazin-1-yl)pyri din-2-yl]sulfanyl}-2- (pyridin-4-yl)acetamide;

2-[(3,5-dicyano-4-ethyl-6-{methyl[2-(morpholin-4-yl)ethyl]am ino}pyridin-2- yl)sulfanyl]-2-phenylacetamide;

2-{[3,5-dicyano-4-ethyl-6-(4-propylpiperazin-1-yl)pyridin-2- yl]sulfanyl}-2- phenylacetamide;

2-({3,5-dicyano-4-ethyl-6-[4-(piperidin-4-yl)piperazin-1-yl] pyridin-2-yl}sulfanyl)-2- phenylacetamide;

2-({3,5-dicyano-4-cyclopropyl-6-[3-(hydroxymethyl)piperazin- 1-yl]pyridin-2- yl}sulfanyl)-2-phenylacetamide;

2-{[3,5-dicyano-4-cyclopropyl-6-(3-oxopiperazin-1-yl)pyridin -2-yl]sulfanyl}-2- phenylacetamide;

2-({3,5-dicyano-4-cyclopropyl-6-[4-(morpholin-4-yl)piperidin -1-yl]pyridin-2- yl}sulfanyl)-2-phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-(2,8-diazaspiro[4.5]decan-8-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-(dimethylamino)piperidin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-methylpiperazin-1-yl)pyri din-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(2-(hydroxymethyl)morpholino )pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(2,6-dimethylmorpholino)pyri din-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(3-(dimethylamino)piperidin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((6-(4-(Aminomethyl)-4-hydroxypiperidin-1-yl)-3,5-dicyano- 4-cyclopropylpyridin- 2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(3-(methylamino)piperidin-1- yl)pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(3-aminopiperidin-1-yl)-3,5-dicyano-4-cyclopropylpyrid in-2-yl)thio)-2- phenylacetamide;

2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-cyclopropylpyrid in-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(4-(dimethylamino)piperidin- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(piperazin-1-yl)pyridin-2-yl )thio)-2-(pyridin-4- yl)acetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(1,4-diazepan-1-yl)pyridin-2 -yl)thio)-2-(pyridin-4- yl)acetamide;

2-((3,5-dicyano-4-cyclopropyl-6-((R)-3-hydroxypiperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide;

2-(3,5-dicyano-4-cyclopropyl-6-((S)-3-hydroxypiperidin-1-yl) pyridin-2-ylthio)-2- phenylacetamide; 2-((3,5-dicyano-4-cyclopropyl-6-((S)-3-hydroxypyrrolidin-1-y l)pyridin-2-yl)thio)-2- (pyridin-4-yl)acetamide;

2-((3,5-dicyano-4-ethyl-6-(4-ethylpiperazin-1-yl)pyridin-2-y l)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(1-oxa-6-azaspiro[3.4]octan-6-yl)p yridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-(3-aminopropyl)piperazin-1-yl)-3,5-dicyano-4-ethylp yridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(1,7-diazaspiro[3.5]nonan-1-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-(pyrrolidin-1-ylmethyl)pi peridin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-(4-methylpiperazin-1-yl)p iperidin-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

(R)-2-((3,5-dicyano-6-(1,4-diazepan-1-yl)-4-ethylpyridin-2-y l)amino)-2- phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-(pyrrolidin-1-yl)piperidi n-1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2,7-diazaspiro[3.5]nonan-7-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2,6-diazaspiro[3.4]octan-6-yl)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-cyclopropyl-6-(1,4-diazepan-1-yl)pyridin-2 -yl)thio)propanamide; 2-((3,5-Dicyano-4-ethyl-6-(4-(2-oxoimidazolidin-1-yl)piperid in-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-hydroxypiperidin-1-yl)pyridin-2 -yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((S)-3-hydroxypyrrolidin-1-yl)pyri din-2-yl)thio)-2- phenylacetamide; 2-((3,5-Dicyano-4-ethyl-6-(3-oxopiperazin-1-yl)pyridin-2-yl) thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((2-methoxyethyl)(methyl)amino)pyr idin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(3-methoxyazetidin-1-yl)pyridin-2- yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(piperazin-1-yl)pyridin-2-yl)thio) -2-phenylacetamide; 2-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-morpholinopyridin-2-yl)thio)-2-phe nylacetamide;

2-[[6-(azetidin-1-yl)-3,5-dicyano-4-ethyl-2-pyridyl]sulfanyl ]-2-phenyl-acetamide; 2-((3,5-dicyano-4-ethyl-6-(4-oxopiperidin-1-yl)pyridin-2-yl) thio)-2-phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-(1'-(2-hydroxyethyl)-[4,4'-bipiper idin]-1-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-((3S,5R)-3,5-dimethylpiperazin-1-yl)-4-eth ylpyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(8-azabicyclo[3.2.1]octan-3-yl(methyl)amino)-3,5-dicya no-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(2-(hydroxymethyl)morpholino )pyridin-2-yl)thio)-2- phenylacetamide;

(R)-2-[(3,5-Dicyano-4-ethyl-6-morpholino-2-pyridyl)sulfanyl] -2-phenyl-acetamide; N-(4-((3,5-Dicyano-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1 -yl)pyridin-2- ylthio)methyl)benzyl)acetamide trifluoroacetate;

2-{[3,5-dicyano-4-ethyl-6-(5-methyl-1,4-diazepan-1-yl)pyridi n-2-yl]sulfanyl}-2- phenylacetamide;

2-({3,5-Dicyano-4-ethyl-6-[4-(2-methoxyethyl)-1,4-diazepa n-1-yl]pyridin-2- yl}sulfanyl)-2-phenylacetamide; 2-((3,5-dicyano-4-ethyl-6-(4-(2-hydroxypropyl)-1,4-diazepan- 1-yl)pyridin-2-yl)thio)- 2-phenylacetamide;

Methyl 2-[4-(6-{[carbamoyl(phenyl)methyl]sulfanyl}-3,5-dicyano-4-et hylpyridin-2- yl)-1,4-diazepan-1-yl]acetate;

2-{[3,5-Dicyano-4-cyclopropyl-6-(4-methyl-5-oxo-1,4-diazepan -1-yl)pyridin-2- yl]sulfanyl}-2-phenylacetamide;

2-{[3,5-Dicyano-4-cyclopropyl-6-(5-oxo-1,4-diazepan-1-yl)pyr idin-2-yl]sulfanyl}-2- phenylacetamide;

2-{[3,5-Dicyano-4-ethyl-6-(4-methyl-5-oxo-1,4-diazepan-1-yl) pyridin-2-yl]sulfanyl}- 2-phenylacetamide;

2-{[3,5-Dicyano-6-(1,4-diazepan-1-yl)-4-ethylpyridin-2-yl]su lfanyl}-2- phenylacetamide;

2-({3,5-Dicyano-6-[4-(2-hydroxyethyl)-1,4-diazepan-1-yl]-4-( 2,2,2- trifluoroethyl)pyridin-2-yl}sulfanyl)-2-phenylacetamide;

(2R)-2-({3,5-Dicyano-4-ethyl-6-[4-(2-hydroxyethyl)-1,4-diaze pan-1-yl]pyridin-2- yl}amino)-2-phenylacetamide;

2-({6-[(3S)-3-Aminopyrrolidin-1-yl]-3,5-dicyano-4-cyclopropy lpyridin-2-yl}sulfanyl)- 2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2,9-diazaspiro[5.5]undecan-9-yl)p yridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(hexahydro-1H-pyrrolo[1,2-a][1,4]d iazepin-2(3H)- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(2-methyl-2,9-diazaspiro[5.5]undec an-9-yl)pyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-6-(2-(cyclopropylmethyl)-2,9-diazaspiro[5.5] undecan-9-yl)-4- ethylpyridin-2-yl)thio)-2-phenylacetamide hydrochloride;

2-((3,5-Dicyano-6-(4-(3-(dimethylamino)propyl)piperazin-1-yl )-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(pyrrolidin-3-yl)piperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide; 2,2,2-trifluoroacetic acid; 2-((6-([4,4'-Bipiperidin]-1-yl)-3,5-dicyano-4-ethylpyridin-2 -yl)thio)-2- phenylacetamide;

2-((6-(4-(2-Aminoethyl)piperazin-1-yl)-3,5-dicyano-4-ethylpy ridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-(3-Aminopropyl)piperazin-1-yl)-3,5-dicyano-4-cyclop ropylpyridin-2-yl)thio)- 2-phenylacetamide;

2-((3,5-Dicyano-4-cyclopropyl-6-(4-((4-methylpiperazin-1-yl) methyl)piperidin-1- yl)pyridin-2-yl)thio)-2-phenylacetamide;

2-((6-(4-Acetylpiperazin-1-yl)-3,5-dicyano-4-ethylpyridin-2- yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-(4-(2-hydroxyethyl)piperazin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-[(3,5-Dicyano-4-cyclopropyl-6-morpholino-2-pyridyl)sulfany l]-2-phenyl- acetamide;

2-((6-(4-Benzoylpiperazin-1-yl)-3,5-dicyano-4-ethylpyridin-2 -yl)thio)-2- phenylacetamide;

2-((3,5-Dicyano-4-ethyl-6-((5S,6S)-6-hydroxy-1-(methylsulfon yl)-1,8- diazaspiro[4.5]decan-8-yl)pyridin-2-yl)thio)-2-phenylacetami de;

2-((3,5-Dicyano-6-(4,4-difluoropiperidin-1-yl)-4-ethylpyridi n-2-yl)thio)-2- phenylacetamide;

(R)-2-((3,5-Dicyano-4-ethyl-6-((R)-3-hydroxypyrrolidin-1-yl) pyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-(furan-2-yl)-6-(4-methyl-1,4-diazepan-1-yl )pyridin-2-yl)thio)-2- phenylacetamide;

2-((6-(4-amino-4-methylpiperidin-1-yl)-3,5-dicyano-4-ethy lpyridin-2-yl)thio)-2- phenylacetamide;

2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)acetamide; (2S)-2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5 -dicyano-4- ethylpyridin-2-yl)piperidin-4-yl)propanamide;

2-((6-(4-(3-aminooxetane-3-carbonyl)piperazin-1-yl)-3,5-dicy ano-4-ethylpyridin-2- yl)thio)-2-phenylacetamide;

4-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)tetrahydro-2H-pyran-4-carboxamide;

2-((6-(4-(4-aminotetrahydro-2H-pyran-4-carbonyl)piperazin-1- yl)-3,5-dicyano-4- ethylpyridin-2-yl)thio)-2-phenylacetamide;

2-((3,5-dicyano-6-(4-(2-hydroxyethyl)-1,4-diazepan-1-yl)-4-m ethoxypyridin-2- yl)thio)-2-phenylacetamide;

2-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2-y l)thio)-2- phenylacetamide;

2-((6-((2-aminoethyl)(methyl)amino)-3,5-dicyano-4-ethylpyrid in-2-yl)thio)-2- phenylacetamide;

2-((6-((2-amino-2-oxoethyl)(methyl)amino)-3,5-dicyano-4-ethy lpyridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(3-hydroxyazetidin-1-yl)pyridin-2- yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-((2-hydroxyethyl)(methyl)amino)pyr idin-2-yl)thio)-2- phenylacetamide;

2-amino-N-(1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicy ano-4-ethylpyridin-2- yl)piperidin-4-yl)-2-methylpropanamide;

2-((6-(4-(2-aminoethoxy)piperidin-1-yl)-3,5-dicyano-4-ethylp yridin-2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(3-hydroxypyrrolidin-1-yl)pyridin- 2-yl)thio)-2- phenylacetamide;

2-((3,5-dicyano-4-ethyl-6-(4-(2-hydroxyethoxy)piperidin-1-yl )pyridin-2-yl)thio)-2- phenylacetamide; or a pharmaceutically acceptable salt or prodrug thereof. Included prodrugs of Formula (Vbbr) of the invention are: 1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)pyrrolidin- 3-yl dihydrogen phosphate;

2-((6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)(methyl)amino)ethyl dihydrogen phosphate;

1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)azetidin- 3-yl dihydrogen phosphate;

(2S)-2-((1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyan o-4-ethylpyridin-2- yl)piperidin-4-yl)oxy)ethyl 2-amino-3-methylbutanoate;

(S)-1-(6-(((S)-2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano -4-ethylpyridin-2- yl)pyrrolidin-3-yl dihydrogen phosphate;

2-((1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-e thylpyridin-2- yl)piperidin-4-yl)oxy)ethyl dihydrogen phosphate; and

1-(6-((2-amino-2-oxo-1-phenylethyl)thio)-3,5-dicyano-4-ethyl pyridin-2-yl)piperidin- 4-yl dihydrogen phosphate; or a pharmaceutically acceptable salt thereof. Non primary amide:

Suitably, presently invented novel compounds of Formula (Icr) are selected from: 2-amino-N-(1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)piperidin-4 -yl)-2-methylpropanamide;

(R)-2-amino-N-(1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)piperidin-4 -yl)propanamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(methyl(2-(piperidin-1-yl)ethy l)amino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((6-(4-Aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin -2- yl)thio)methyl)benzyl)acetamide;

2-(4-aminopiperidin-1-yl)-6-((4-(1,1-dioxidoisothiazolidin-2 -yl)benzyl)thio)-4- ethylpyridine-3,5-dicarbonitrile; 2-(4-aminopiperidin-1-yl)-6-((4-(1,1-dioxido-1,2-thiazinan-2 -yl)benzyl)thio)-4- ethylpyridine-3,5-dicarbonitrile;

2-(4-aminopiperidin-1-yl)-4-ethyl-6-((4- ((methylsulfonyl)methyl)benzyl)thio)pyridine-3,5-dicarbonitr ile;

4-(((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2- yl)thio)methyl)phenyl methanesulfonate;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-(isopropylamino)piperidin-1 -yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin -2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-((3,5-Dicyano-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1 -yl)pyridin-2- ylthio)methyl)benzyl)acetamide;

2-amino-N-(4-(((3,5-dicyano-6-((2-(diethylamino)ethyl)(methy l)amino)-4- ethylpyridin-2-yl)thio)methyl)benzyl)acetamide;

rel-2-amino-N-(4-(((6-(cis-4-amino-3-fluoropiperidin-1-yl)-3 ,5-dicyano-4- ethylpyridin-2-yl)thio)methyl)benzyl)acetamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(2-(pyrrolidin-1-ylmethyl)morp holino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl) acetamide; and N-(4-(((3,5-dicyano-6-(3-((dimethylamino)methyl)piperidin-1- yl)-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide; or a pharmaceutically acceptable salt or prodrug thereof.

Suitably, presently invented novel compounds of Formula (Icr) are selected from: N-(4-((3,5-Dicyano-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin-1 -yl)pyridin-2- ylthio)methyl)benzyl)acetamide;

2-(4-(Aminomethyl)benzylthio)-4-ethyl-6-(4-(pyrrolidin-1-yl) piperidin-1-yl)pyridine- 3,5-dicarbonitrile; tert-Butyl 4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2- yl)thio)methyl)benzylcarbamate;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2- yl)thio)methyl)benzamide;

2-((4-(Aminomethyl)benzyl)thio)-4-ethyl-6-(4-methyl-1,4-diaz epan-1-yl)pyridine- 3,5-dicarbonitrile;

2-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)phenyl)acetic acid;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2- yl)thio)methyl)benzoic acid;

2-(Dimethylamino)-4-ethyl-6-(((6-oxo-1,6-dihydropyridin-3-yl )methyl)thio)pyridine- 3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)thiazol-2-yl)acetamide;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2- yl)thio)methyl)benzenesulfonamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl) acetamide;

tert-Butyl (2-((4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl) pyridin-2- yl)thio)methyl)benzyl)amino)-2-oxoethyl)carbamate;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)methanesulfonamide;

2-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan -1-yl)pyridin-2- yl)thio)methyl)benzyl)acetamide;

2-(4-Aminopiperidin-1-yl)-6-(benzylthio)-4-ethylpyridine-3, 5-dicarbonitrile;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2- yl)thio)methyl)benzyl acetate;

2-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)phenyl acetamide; 2-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)phenyl)-N-methylacetamide;

4-Ethyl-2-((4-(hydroxymethyl)benzyl)thio)-6-(4-methyl-1,4-di azepan-1-yl)pyridine- 3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)-2-hydroxyacetamide;

Example 87N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl) pyridin-2-yl)thio) methyl)benzyl)propionamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)isobutyramide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)-3-methylbutanamide;

4-Ethyl-2-((4-(((2-hydroxyethyl)amino)methyl)benzyl)thio)-6- (4-methyl-1,4- diazepan-1-yl)pyridine-3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-6-(4-methyl-1,4-diazepan-1-yl)-4-(methyl amino)pyridin-2- yl)thio)methyl)benzyl)acetamide;

2-(((2-Acetyl-1,2,3,4-tetrahydroisoquinolin-6-yl)methyl)thio )-6-(dimethylamino)-4- ethylpyridine-3,5-dicarbonitrile;

2-((4-Cyanobenzyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1-y l)pyridine-3,5- dicarbonitrile;

2-Amino-N-(1-(6-(benzylthio)-3,5-dicyano-4-ethylpyridin-2-yl )piperidin-4- yl)acetamide;

2-Amino-N-(1-(6-(benzylthio)-3,5-dicyano-4-ethylpyridin-2-yl )piperidin-4-yl)-2- methylpropanamide;

3-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan -1-yl)pyridin-2- yl)thio)methyl)benzyl)propanamide;

(S)-2-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diaz epan-1-yl)pyridin-2- yl)thio)methyl)benzyl)propanamide;

(R)-2-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diaz epan-1-yl)pyridin-2- yl)thio)methyl)benzyl)propanamide; 1-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)-3-ethylurea;

1-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)-3-phenylurea;

N-(4-(((3,5-Dicyano-6-(4-methyl-1,4-diazepan-1-yl)-4-(methyl thio)pyridin-2- yl)thio)methyl)benzyl)acetamide;

(E)-3-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2- yl)thio)methyl)phenyl)acrylic acid;

N-(4-(((3,5-Dicyano-4-ethyl-6-((2-hydroxyethyl)(methyl)amino )pyridin-2- yl)thio)methyl)benzyl)acetamide;

4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2-yl)thio)methyl)-N- methylbenzenesulfonamide;

N-(4-(((3,5-Dicyano-4-ethoxy-6-(4-methyl-1,4-diazepan-1-yl)p yridin-2- yl)thio)methyl)benzyl)acetamide;

N-(4-(((6-(4-Aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin -2- yl)thio)methyl)benzyl)acetamide;

(S)-2-((1-(6-((4-(Acetamidomethyl)benzyl)thio)-3,5-dicyano-4 -ethylpyridin-2- yl)piperidin-4-yl)oxy)ethyl 2-amino-3-methylbutanoate;

(S)-2-((6-((4-(Acetamidomethyl)benzyl)thio)-3,5-dicyano-4-et hylpyridin-2- yl)(methyl)amino)ethyl 2-amino-3-methylbutanoate;

2-Amino-N-(4-(((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin -2- yl)thio)methyl)benzyl)acetamide;

4-Ethyl-2-(4-methyl-1,4-diazepan-1-yl)-6-((4-((2-oxopyrrolid in-1- yl)methyl)benzyl)thio)pyridine-3,5-dicarbonitrile;

2-((4-(Aminomethyl)benzyl)thio)-6-(dimethylamino)-4-ethylpyr idine-3,5- dicarbonitrile;

N-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl) thio) methyl) phenyl) acetamide;

N-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)th io)methyl)benzyl)-2- hydroxyacetamide; 3-Amino-N-(4-(((3,5-dicyano-6-(dimethylamino)-4-ethylpyridin -2- yl)thio)methyl)benzyl)propanamide;

(S)-1-(6-((4-(Acetamidomethyl)benzyl)thio)-3,5-dicyano-4-eth ylpyridin-2- yl)azetidin-3-yl 2-amino-3-methylbutanoate;

N-(4-(((3,5-Dicyano-4-ethyl-6-methylpyridin-2-yl)thio)methyl )benzyl)acetamide; 2-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)th io)methyl)-1H-pyrazol- 1-yl)acetamide;

N-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)th io)methyl)phenyl) methanesulfonamide;

(S)-1-(6-((4-(Acetamidomethyl)benzyl)thio)-3,5-dicyano-4-eth ylpyridin-2- yl)piperidin-4-yl 2-amino-3-methylbutanoate;

N-(1-(6-((4-(Acetamidomethyl)benzyl)thio)-3,5-dicyano-4-ethy lpyridin-2- yl)piperidin-4-yl)acetamide;

2-(4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)th io)methyl)phenyl)-N-(2- hydroxyethyl)acetamide;

4-(((3,5-Dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl)thio) methyl)-N-(2- hydroxyethyl)benzamide;

2-((4-(1H-Imidazol-1-yl)benzyl)thio)-4-ethyl-6-(4-methyl-1,4 -diazepan-1- yl)pyridine-3,5-dicarbonitrile;

2-((4-Cyano-3-methylbenzyl)thio)-4-ethyl-6-(4-methyl-1,4-dia zepan-1-yl)pyridine- 3,5-dicarbonitrile;

tert-Butyl(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan -1-yl)pyridin-2- yl)thio)methyl)phenyl)carbamate;

2-((4-Aminobenzyl)thio)-4-ethyl-6-(4-methyl-1,4-diazepan-1-y l)pyridine-3,5- dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)phenyl)acetamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)phenyl) methanesulfonamide; 2-(((6-Aminopyridin-3-yl)methyl)thio)-4-ethyl-6-(4-methyl-1, 4-diazepan-1- yl)pyridine-3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)phenyl)-2-hydroxyacetamide;

2-Amino-N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan -1-yl)pyridin-2- yl)thio)methyl)phenyl)acetamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(3-oxopiperazin-1-yl)pyridin-2 -yl)thio) methyl) benzyl) acetamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(3-hydroxypyrrolidin-1-yl)pyri din-2- yl)thio)methyl)benzyl)acetamide;

N-(4-(1-(3,5-Dicyano-6-(4-(dimethylamino)piperidin-1-yl)-4-e thylpyridin-2- ylthio)propyl)benzyl)acetamide;

N-(5-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)pyridin-2-yl)methanesulfonamide;

2-(6-(4-(Acetamidomethyl)benzylthio)-3,5-dicyano-4-ethylpyri din-2-ylthio)-2- phenylacetamide;

4-Ethyl-2-((4-(pyridin-3-yl)benzyl)thio)-6-(4-(pyrrolidin-1- yl)piperidin-1-yl)pyridine- 3,5-dicarbonitrile;

4-Ethyl-2-((4-(pyridin-4-yl)benzyl)thio)-6-(4-(pyrrolidin-1- yl)piperidin-1-yl)pyridine- 3,5-dicarbonitrile;

2-Amino-N-(1-(3,5-dicyano-4-ethyl-6-((4-sulfamoylbenzyl)thio )pyridin-2- yl)piperidin-4-yl)acetamide;

2-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)phenyl)-N-(2-hydroxyethyl)acetamide;

2-(((1H-Indol-5-yl)methyl)thio)-4-ethyl-6-(4-(pyrrolidin-1-y l)piperidin-1-yl)pyridine- 3,5-dicarbonitrile;

4-(((6-(4-Aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2- yl)thio)methyl) benzenesulfonamide;

2-((Benzo[d][1,3]dioxol-5-ylmethyl)thio)-4-ethyl-6-(4-methyl -1,4-diazepan-1- yl)pyridine-3,5-dicarbonitrile; 2-(((3,3-Dimethoxy-2-oxoindolin-5-yl)methyl)thio)-4-ethyl-6- (4-methyl-1,4- diazepan-1-yl)pyridine-3,5-dicarbonitrile;

2-(((2,3-Dioxoindolin-5-yl)methyl)thio)-4-ethyl-6-(4-methyl- 1,4-diazepan-1- yl)pyridine-3,5-dicarbonitrile;

N-(4-(((6-(((4H-1,2,4-Triazol-3-yl)methyl)(methyl)amino)-3,5 -dicyano-4- ethylpyridin-2-yl)thio)methyl)benzyl)acetamide;

4-Ethyl-2-((4-(pyridin-2-yl)benzyl)thio)-6-(4-(pyrrolidin-1- yl)piperidin-1-yl)pyridine- 3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)phenyl)-N-methylacetamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2-yl) thio)methyl)phenyl)-N-methylmethanesulfonamide;

4-((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyridi n-2- ylthio)methyl)phenylboronic acid;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)benzyl)-2-(methylamino)acetamide;

2-((4-Amino-3-fluorobenzyl)thio)-4-ethyl-6-(4-methyl-1,4-dia zepan-1-yl)pyridine- 3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)-2-fluorophenyl)methanesulfonamide;

N-(4-(((3,5-Dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2-yl) thio)methyl)-2-fluorophenyl)acetamide;

2-(4-Aminopiperidin-1-yl)-4-ethyl-6-(((1-(2-hydroxyethyl)-1H -pyrazol-4- yl)methyl)thio)pyridine-3,5-dicarbonitrile;

N-(4-(((3,5-Dicyano-4-ethyl-6-(3-hydroxypyrrolidin-1-yl)pyri din-2- yl)thio)methyl)benzyl)-2-hydroxyacetamide;

N-(4-(((6-((2-Amino-2-oxoethyl) (methyl) amino)-3, 5-dicyano-4-ethylpyridin-2-yl) thio) methyl) benzyl)-2-hydroxyacetamide;

2-(4-(2-(Dimethylamino)ethoxy)benzylthio)-4-ethyl-6-(4-methy l-1,4-diazepan-1- yl)pyridine-3,5-dicarbonitrile; 4-Ethyl-2-(4-methyl-1,4-diazepan-1-yl)-6-((4-(methylsulfonyl )benzyl)thio)pyridin e-3,5-dicarbonitrile;

2-(4-Aminopiperidin-1-yl)-6-(((1-(2, 3-dihydroxypropyl)-1H-pyrazol-4- yl)methyl)thio)-4-ethylpyridine-3,5-dicarbonitrile;

4-Ethyl-2-(4-methyl-1,4-diazepan-1-yl)-6-((4-(4-methylpipera zin-1- yl)benzyl)thio)pyridine-3,5-dicarbonitrile;

4-Ethyl-2-(4-methyl-1,4-diazepan-1-yl)-6-((4-(((2-oxopyrroli din-3- yl)amino)methyl)benzyl)thio)pyridine-3,5-dicarbonitrile;

2-(((1H-Benzo[d]imidazol-5-yl)methyl)thio)-4-ethyl-6-(4-meth yl-1,4-diazepan-1- yl)pyridine-3,5-dicarbonitrile;

4-Ethyl-2-(4-methyl-1,4-diazepan-1-yl)-6-(4- (methylsulfonylmethyl)benzylthio)pyridine-3,5-dicarbonitrile ;

2-{[3,5-dicyano-6-(dimethylamino)-4-ethylpyridin-2-yl]sulfan yl}-2-phenylacetamide; N-(4-(((3,5-dicyano-4-ethyl-6-(methyl(2-(neopentylamino)ethy l)amino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-((2-((2- methoxyethyl)(methyl)amino)ethyl)(methyl)amino)pyridin-2-yl) thio)methyl)phenyl)-N- methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(methyl(2-(methylamino)ethyl)a mino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-((2-((2- methoxyethyl)amino)ethyl)(methyl)amino)pyridin-2-yl)thio)met hyl)phenyl)-N- methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(methyl(2-((1- methylcyclopropyl)amino)ethyl)amino)pyridin-2-yl)thio)methyl )phenyl)-N- methylmethanesulfonamide;

N-(4-(((3,5-dicyano-6-((2-(dimethylamino)ethyl)(methyl)amino )-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((6-((2-aminoethyl)(methyl)amino)-3,5-dicyano-4-ethylp yridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide; 2-(4-aminopiperidin-1-yl)-4-ethyl-6-((4- ((methylsulfonyl)methyl)benzyl)thio)pyridine-3,5-dicarbonitr ile;

N-(4-(((3,5-dicyano-4-ethyl-6-((2-((2- fluoroethyl)amino)ethyl)(methyl)amino)pyridin-2-yl)thio)meth yl)phenyl)-N- methylmethanesulfonamide;

2-amino-N-(4-(((3,5-dicyano-6-((2-(diethylamino)ethyl)(methy l)amino)-4- ethylpyridin-2-yl)thio)methyl)benzyl)acetamide;

4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)pyrid in-2-yl)thio)methyl)-N- (1H-pyrazol-4-yl)benzamide;

rel-2-amino-N-(4-(((6-(cis-4-amino-3-fluoropiperidin-1-yl)-3 ,5-dicyano-4- ethylpyridin-2-yl)thio)methyl)benzyl)acetamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-(isopropylamino)piperidin-1 -yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-((2-methoxyethyl)amino)pipe ridin-1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-(neopentylamino)piperidin-1 -yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(methyl(2-(pyrrolidin-1-yl)eth yl)amino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-6-(2-((dimethylamino)methyl)morpholino)- 4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

2-amino-N-(1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)piperidin-4 -yl)-2-methylpropanamide;

N-(4-(((3,5-dicyano-6-(4-(cyclopropylamino)piperidin-1-yl)-4 -ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(2-(pyrrolidin-1-ylmethyl)morp holino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(methyl(2-(piperidin-1-yl)ethy l)amino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide; N-(4-(((3,5-dicyano-6-((2-(diethylamino)ethyl)(methyl)amino) -4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-6-(2-((diethylamino)methyl)morpholino)-4 -ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-(pyrrolidin-1-yl)piperidin- 1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

(R)-2-amino-N-(1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)piperidin-4 -yl)propanamide;

(S)-2-amino-N-(1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)piperidin-4 -yl)propanamide;

N-(4-(((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin -2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

2-amino-N-(1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)piperidin-4 -yl)acetamide;

N-(4-(((6-(2-(aminomethyl)morpholino)-3,5-dicyano-4-ethylpyr idin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)phenyl)-1-fluoro-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-4-ethyl-6-(2-((methylamino)methyl)morpho lino)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((3,5-dicyano-6-(3-((dimethylamino)methyl)piperidin-1- yl)-4-ethylpyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide;

2-(4-aminopiperidin-1-yl)-6-((4-(1,1-dioxidoisothiazolidin-2 -yl)benzyl)thio)-4- ethylpyridine-3,5-dicarbonitrile;

2-(4-aminopiperidin-1-yl)-6-((4-(1,1-dioxido-1,2-thiazinan-2 -yl)benzyl)thio)-4- ethylpyridine-3,5-dicarbonitrile;

N-(4-(((3,5-dicyano-4-ethyl-6-(4-methyl-1,4-diazepan-1-yl)py ridin-2- yl)thio)methyl)phenyl)-1,1-difluoro-N-methylmethanesulfonami de;

2-((4-(1,1-dioxidoisothiazolidin-2-yl)benzyl)thio)-4-ethyl-6 -(4- (neopentylamino)piperidin-1-yl)pyridine-3,5-dicarbonitrile; 2-((4-(1,1-dioxido-1,2-thiazinan-2-yl)benzyl)thio)-4-ethyl-6 -(4- (neopentylamino)piperidin-1-yl)pyridine-3,5-dicarbonitrile;

4-(((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyridin-2- yl)thio)methyl)phenyl methanesulfonate;

(R)-2-amino-N-((1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)pyrrolidin- 3-yl)methyl)acetamide;

(S)-2-amino-N-((1-(3,5-dicyano-4-ethyl-6-((4-(N- methylmethylsulfonamido)benzyl)thio)pyridin-2-yl)pyrrolidin- 3-yl)methyl)acetamide;

N-(4-(1-((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-ethylpyrid in-2- yl)thio)ethyl)phenyl)-N-methylmethanesulfonamide;

N-(4-(((6-(4-aminopiperidin-1-yl)-3,5-dicyano-4-methoxypyrid in-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide; and

N-(4-(((3,5-dicyano-4-ethyl-6-(4-((2-hydroxyethyl)amino)pipe ridin-1-yl)pyridin-2- yl)thio)methyl)phenyl)-N-methylmethanesulfonamide; or a pharmaceutically acceptable salt or prodrug thereof. The skilled artisan will appreciate that pharmaceutically acceptable salts, of the compounds according to Formula (I) may be prepared. Indeed, in certain embodiments of the invention pharmaceutically acceptable salts of the compounds according to Formula (I) may be preferred over the respective free or unsalted compound. Accordingly, the invention is further directed to pharmaceutically acceptable salts, of the compounds according to Formula (I). The invention is further directed to free or unsalted compounds of Formula (I). The pharmaceutically acceptable salts of the compounds of the invention are readily prepared by those of skill in the art. Representative pharmaceutically acceptable acid addition salts include, but are not limited to, 4-acetamidobenzoate, acetate, adipate, alginate, ascorbate, aspartate, benzenesulfonate (besylate), benzoate, bisulfate, bitartrate, butyrate, calcium edetate, camphorate, camphorsulfonate (camsylate), caprate (decanoate), caproate (hexanoate), caprylate (octanoate), cinnamate, citrate, cyclamate, digluconate, 2,5-dihydroxybenzoate, disuccinate, dodecylsulfate (estolate), edetate (ethylenediaminetetraacetate), estolate (lauryl sulfate), ethane-1,2-disulfonate (edisylate), ethanesulfonate (esylate), formate, fumarate, galactarate (mucate), gentisate (2,5-dihydroxybenzoate), glucoheptonate (gluceptate), gluconate, glucuronate, glutamate, glutarate, glycerophosphorate, glycolate, hexylresorcinate, hippurate, hydrabamine (N,N'-di(dehydroabietyl)-ethylenediamine), hydrobromide, hydrochloride, hydroiodide, hydroxynaphthoate, isobutyrate, lactate, lactobionate, laurate, malate, maleate, malonate, mandelate, methanesulfonate (mesylate), methylsulfate, mucate, naphthalene-1,5-disulfonate (napadisylate), naphthalene-2-sulfonate (napsylate), nicotinate, nitrate, oleate, palmitate, p- aminobenzenesulfonate, p-aminosalicyclate, pamoate (embonate), pantothenate, pectinate, persulfate, phenylacetate, phenylethylbarbiturate, phosphate, polygalacturonate, propionate, p-toluenesulfonate (tosylate), pyroglutamate, pyruvate, salicylate, sebacate, stearate, subacetate, succinate, sulfamate, sulfate, tannate, tartrate, teoclate (8-chlorotheophyllinate), thiocyanate, triethiodide, undecanoate, undecylenate, and valerate. Representative pharmaceutically acceptable base addition salts include, but are not limited to, aluminium, 2-amino-2-(hydroxymethyl)-1,3-propanediol (TRIS, tromethamine), arginine, benethamine (N-benzylphenethylamine), benzathine (N,N’- dibenzylethylenediamine), bis-(2-hydroxyethyl)amine, bismuth, calcium, chloroprocaine, choline, clemizole (1-p chlorobenzyl-2-pyrrolildine-1’-ylmethylbenzimidazole), cyclohexylamine, dibenzylethylenediamine, diethylamine, diethyltriamine, dimethylamine, dimethylethanolamine, dopamine, ethanolamine, ethylenediamine, L-histidine, iron, isoquinoline, lepidine, lithium, lysine, magnesium, meglumine (N-methylglucamine), piperazine, piperidine, potassium, procaine, quinine, quinoline, sodium, strontium, t- butylamine, and zinc. The compounds according to Formula (I) may contain one or more asymmetric centers (also referred to as a chiral center) and may, therefore, exist as individual enantiomers, diastereomers, or other stereoisomeric forms, or as mixtures thereof. Chiral centers, such as chiral carbon atoms, may be present in a substituent such as an alkyl group. Where the stereochemistry of a chiral center present in a compound of Formula (I), or in any chemical structure illustrated herein, is not specified the structure is intended to encompass all individual stereoisomers and all mixtures thereof. Thus, compounds according to Formula (I) containing one or more chiral centers may be used as racemic mixtures, enantiomerically enriched mixtures, or as enantiomerically pure individual stereoisomers. The compounds according to Formula (I) and pharmaceutically acceptable salts thereof may contain isotopically-labelled compounds, which are identical to those recited in Formula (I) and following, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of such isotopes include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulphur, fluorine, iodine, and chlorine, such as 2 H, 3 H, 11 C, 13 C, 14 C, 15 N, 17 O, 18 O, 31 P, 32 P, 35 S, 18 F, 36 Cl, 123 I and 125 I.

Isotopically-labelled compounds, for example those into which radioactive isotopes such as 3 H or 14 C are incorporated, are useful in drug and/or substrate tissue distribution assays. Tritium, i.e., 3 H, and carbon-14, i.e., 14 C, isotopes are particularly preferred for their ease of preparation and detectability. 11 C and 18 F isotopes are particularly useful in PET (positron emission tomography), and 125 I isotopes are particularly useful in SPECT (single photon emission computerized tomography), both are useful in brain imaging. Further, substitution with heavier isotopes such as deuterium, i.e., 2 H, can afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and, hence, may be preferred in some circumstances. Isotopically labelled compounds can generally be prepared by substituting a readily available isotopically labelled reagent for a non-isotopically labelled reagent. The compounds according to Formula (I) may also contain double bonds or other centers of geometric asymmetry. Where the stereochemistry of a center of geometric asymmetry present in Formula (I), or in any chemical structure illustrated herein, is not specified, the structure is intended to encompass the trans (E) geometric isomer, the cis (Z) geometric isomer, and all mixtures thereof. Likewise, all tautomeric forms are also included in Formula (I) whether such tautomers exist in equilibrium or predominately in one form. The compounds of the invention may exist in solid or liquid form. In solid form, compound of the invention may exist in a continuum of solid states ranging from fully amorphous to fully crystalline. The term‘amorphous’ refers to a state in which the material lacks long range order at the molecular level and, depending upon the temperature, may exhibit the physical properties of a solid or a liquid. Typically such materials do not give distinctive X- ray diffraction patterns and, while exhibiting the properties of a solid, are more formally described as a liquid. Upon heating, a change from solid to liquid properties occurs which is characterized by a change of state, typically second order (‘glass transition’). The term ‘crystalline’ refers to a solid phase in which the material has a regular ordered internal structure at the molecular level and gives a distinctive X-ray diffraction pattern with defined peaks. Such materials when heated sufficiently will also exhibit the properties of a liquid, but the change from solid to liquid is characterized by a phase change, typically first order (‘melting point’). The compounds of the invention may have the ability to crystallize in more than one form, a characteristic, which is known as polymorphism (“polymorphs”). Polymorphism generally can occur as a response to changes in temperature or pressure or both and can also result from variations in the crystallization process. Polymorphs can be distinguished by various physical characteristics known in the art such as x-ray diffraction patterns, solubility and melting point. The compounds of Formula (I) may exist in solvated and unsolvated forms. As used herein, the term“solvate” refers to a complex of variable stoichiometry formed by a solute (in this invention, a compound of Formula (I) or a salt) and a solvent. Such solvents, for the purpose of the invention, may not interfere with the biological activity of the solute. The skilled artisan will appreciate that pharmaceutically acceptable solvates may be formed for crystalline compounds wherein solvent molecules are incorporated into the crystalline lattice during crystallization. The incorporated solvent molecules may be water molecules or non-aqueous such as ethanol, isopropanol, DMSO, acetic acid, ethanolamine, and ethyl acetate molecules. Crystalline lattice structures incorporated with water molecules are typically referred to as“hydrates”. Hydrates include stoichiometric hydrates as well as compositions containing variable amounts of water. It is also noted that the compounds of Formula (I) may form tautomers.‘Tautomers’ refer to compounds that are interchangeable forms of a particular compound structure, and that vary in the displacement of hydrogen atoms and electrons. Thus, two structures may be in equilibrium through the movement of π electrons and an atom (usually H). For example, enols and ketones are tautomers because they are rapidly interconverted by treatment with either acid or base. It is understood that all tautomers and mixtures of tautomers of the compounds of the present invention are included within the scope of the compounds of the present invention. While aspects for each variable have generally been listed above separately for each variable this invention includes those compounds in which several or each aspect in Formula (I) is selected from each of the aspects listed above. Therefore, this invention is intended to include all combinations of aspects for each variable. DEFINITIONS

It will be appreciated that the following definitions apply to each of the aforementioned formulae and to all instances of these terms, unless the context dictates otherwise.

“Alkyl” refers to a hydrocarbon chain having the specified number of“member atoms”. For example, C 1 -C 6 alkyl refers to an alkyl group having from 1 to 6 member atoms. Alkyl groups may be saturated, unsaturated, straight or branched. Representative branched alkyl groups have one, two, or three branches. Alkyl includes but is not limited to: methyl, ethyl, ethylenyl, propyl (n-propyl and isopropyl), butenyl, butyl (n-butyl, isobutyl, and t-butyl), pentyl and hexyl.

“Alkoxy” refers to an -O-alkyl group wherein“alkyl” is as defined herein. For example, C 1 -C 4 alkoxy refers to an alkoxy group having from 1 to 4 carbon member atoms.

Examples of such groups include but is not limited to: methoxy, ethoxy, propoxy, butoxy, and t-butoxy. “Aryl” refers to an aromatic hydrocarbon ring system. Aryl groups are monocyclic, bicyclic, and tricyclic ring systems having a total of five to fourteen ring member atoms, wherein at least one ring system is aromatic and wherein each ring in the system contains 3 to 7 member atoms, such as but no limited to: phenyl, dihydroindene, naphthalene, tetrahydronaphthalene and biphenyl. Suitably aryl is phenyl. Cycloalkyl”, unless otherwise defined, refers to a saturated or unsaturated non aromatic hydrocarbon ring or rings having from three to seven carbon atoms. Cycloalkyl groups are monocyclic or spiro ring systems. For example, C 3 -C 7 cycloalkyl refers to a cycloalkyl group having from 3 to 7 member atoms. Examples of cycloalkyl as used herein include but is not limited to: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, spiro heptanyl and cycloheptyl. Suitably cycloalkyl is selected from: cyclopropyl, cyclopentyl and cyclohexyl.

"Heteroaryl” refers to a monocyclic aromatic 4 to 8 member ring containing from 1 to 7 carbon atoms and containing from 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur, provided that when the number of carbon atoms is 3, the aromatic ring contains at least two heteroatoms, or to such aromatic ring is fused one or more rings, such as heteroaryl rings, aryl rings, heterocyclic rings, or cycloalkyl rings. Heteroaryl groups containing more than one heteroatom may contain different heteroatoms. Heteroaryl includes but is not limited to: benzoimidazolyl, benzothiazolyl, benzothiophenyl, benzopyrazinyl, benzotriazolyl, benzotriazinyl, benzo[1,4]dioxanyl, benzofuranyl, 9H-a-carbolinyl, cinnolinyl, furanyl, imidazolyl, oxazoly, indazolyl, indolizinyl, indolyl, isoindolyl, isothiazolyl, isoquinolinyl, isoxazolyl, indolizinyl, naphthyridinyl, oxazolyl, oxothiadiazolyl, oxadiazolyl, phthalazinyl, pyridyl, pyrrolyl, purinyl, pteridinyl, phenazinyl, pyrazolyl, pyrazolopyrimidinyl, pyrazolopyridinyl, pyrrolizinyl, pyridazyl, pyrazinyl, pyrimidyl, quinoxalinyl, quinazolinyl, quinolinyl, quinolizinyl, thienyl, thiophenyl, triazolyl, triazinyl, tetrazolopyrimidinyl, triazolopyrimidinyl, tetrazolyl, thiadiazolyl, thiazolyl and thiazolidinyl. Suitably heteroaryl is selected from: furanyl, pyrazolyl, pyrrolyl, imidazolyl, isoxazolyl, isothiazolyl, oxazolyl, triazolyl, thiazolyl and thienyl. Suitably heteroaryl is a pyridyl group or an imidazolyl group. Suitably heteroaryl is a pyridyl.

“Heterocyclic” or“heterocycloalkyl”, as used herein, unless otherwise defined, refers to a saturated or unsaturated non-aromatic ring containing 4 to 12 member atoms, of which 1 to 11 are carbon atoms and from 1 to 6 are heteroatoms independently selected from nitrogen, oxygen and sulfur. Heterocycloalkyl groups containing more than one heteroatom may contain different heteroatoms. Such ring may be optionally fused to one or more other“heterocyclic” rings, aryl rings, heteroaryl rings, or cycloalkyl rings. Such rings may be bridged bicyclic or spiro. Examples of“heterocyclic” groups include, but are not limited to: 1,4diazepanyl, azetidinyl, oxetanyl, 1,4-dioxanyl, 1,3-dioxanyl, pyrrolidinyl, pyrrolidin-2-onyl, piperidinyl, piperazinyl, piperazinyl-2,5-dionyl, morpholinyl, dihydropyranyl, dihydrocinnolinyl, dihydropyridinyl, tetrahydropyranyl, 2,3-dihydrofuranyl, 2,3-dihydrobenzofuranyl, dihydroisoxazolyl, tetrahydrooxazolyl, tetrahydrofuranyl, tetrahydrothiazolyl, tetrahydrothiazinyl, tetrahydrothiopyranyl, tetrahydrothiophenyl, dihydroquinoxalinyl, tetrahydroquinoxalinyl, tetrahydroisoquinolinyl, tetrahydropyridinyl, tetrahydrocarbolinyl, 2,9-diazaspiro[5.5]undecanyl, 1,8-diazaspiro[4.5]decanyl, 2,8- diazaspiro[4.5]decanyl, hexahydropyrrolo-1,4-diazepanyl, 1-oxa-6-azaspiro[3.4]octanyl, 5- oxa-2-azaspiro[3.4]octanyl, 1,7-diazaspiro[3.5]nonanyl, 2,7-diazaspiro[3.5]nonanyl, 2,6- diazaspiro[3.4]octanyl, 1,8-diazaspiro[4.5]decanyl and 8-azabicyclo[3.2.1]octanyl. Suitably heterocyclic is selected from: 1,4-diazepanyl, azetidinyl, oxetanyl, pyrrolidinyl, dihydropyridinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydroisoquinolinyl, tetrahydropyranyl, 2,9-diazaspiro[5.5]undecanyl, 1,8-diazaspiro[4.5]decanyl, 2,8- diazaspiro[4.5]decanyl, hexahydropyrrolo-1,4-diazepanyl, 1-oxa6-azaspiro[3.4]octanyl, 5- oxa-2-azaspiro[3.4]octanyl, 1,7-diazaspiro[3.5]nonanyl, 2,7-diazaspiro[3.5]nonanyl, 2,6- diazaspiro[3.4]octanyl, 1,8-diazaspiro[4.5]decanyl and 8-azabicyclo[3.2.1]octanyl.

“Heteroatom” refers to a nitrogen, sulphur or oxygen atom.

“Halogen” and“halo” refers to a fluorine, chlorine, bromine, or iodine atom.

As used herein, the term“mercapto” refers to the group–SH.

As used herein, the term“oxo” refers to the group =O.

As used herein, the term“hydroxy” refers to the group–OH.

As used herein, the term“amino” refers to the group–NH 2 . As used herein, the term“aminocarbonyl” refers to the group–C(O)NH 2 .

As used herein, the term“guanidino” refers to the group–NHC(=NH)NH 2 .

As used herein, the term“carboxy” refers to the group–C(O)OH.

As used herein, the term“cyano” refers to the group–-CN.

As used herein, the term“prodrug” refers to a compound that is metabolized in the body to produce a biologically active compound. This more biologically active compound is refered to herein as an“active compound”. An example of a prodrug of the invention is the compound of Example 151. An example of the corresponding active compound is the compound of Example 147.

As used herein, the term“active compound” refers to a compound inhibits the activity of DNMT1, suitably a compound that is a selective inhibitor of DNMT1.

As used herein, the term“selective”, when referring to chemical compounds, suitably the active compounds of the present invention, means the compounds exhibit an IC50 over 30 times more active, suitably over 50 times more active, suitably over 100 times more active as an inhibitor against DNMT1, than DNMT3A or DNMT3B in the Breaklight Assay described herein or a similar assay.

As used herein, the term “Compound A” refers to: 2-{[3,5-dicyano-6- (dimethylamino)-4-ethylpyridin-2-yl]sulfanyl}-2-phenylacetam ide, the compound of Example 3.

As used herein the symbols and conventions used in these processes, schemes and examples are consistent with those used in the contemporary scientific literature, for example, the Journal of the American Chemical Society or the Journal of Biological Chemistry. Standard single-letter or three-letter abbreviations are generally used to designate amino acid residues, which are assumed to be in the L-configuration unless otherwise noted. Unless otherwise noted, all starting materials were obtained from commercial suppliers and used without further purification. Specifically, the following abbreviations may be used in the examples and throughout the specification:

Ac (acetyl);

Ac 2 O (acetic anhydride);

A-CN (acetonitrile);

AIBN (azobis(isobutyronitrile));

BINAP (2,2'-bis(diphenylphosphino)-1,1'-binaphthyl);

BMS (borane -