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Title:
ANTIBACTERIAL AGENTS
Document Type and Number:
WIPO Patent Application WO/2004/062601
Kind Code:
A2
Abstract:
Antibacterial compounds of formula (I) are provided: As well as stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of the compounds.

Inventors:
Anderson, Neils H. (6529 Greenwood Avenue N, Seattle, WA, 98103, US)
Bowman, Jason (4810 Elm Street, Quincy, IL, 62305, US)
Erwin, Alice (Chiron Corporation, 4560 Horton Street Emeryville, CA, 94608, US)
Harwood, Eric (Chiron Corporation, 4560 Horton Street Emeryville, CA, 94608, US)
Kline, Toni (Chiron Corporation, 4560 Horton Street Emeryville, CA, 94608, US)
Mdluli, Khisimuzi (Chiron Corporation, 4560 Horton Street Emeryville, Ca, 94608, US)
Simon NG. (Chiron Corporation, 4560 Horton Street Emeryville, CA, 94608, US)
Pfister, Keith B. (Chiron Corporation, 4560 Horton Street Emeryville, CA, 94608, US)
Shawar, Ribhi (Chiron Corporation, 4560 Horton Street Emeryville, CA, 94608, US)
Wagman, Allan (Chiron Corporation, 4560 Horton Street Emeryville, CA, 94608, US)
Yabannavar, Asha (Chiron Corpoartion, 4560 Horton Street Emeryville, CA, 94608, US)
Application Number:
PCT/US2004/000433
Publication Date:
July 29, 2004
Filing Date:
January 08, 2004
Export Citation:
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Assignee:
CHIRON CORPORATION (4560 Horton Street, Emeryville, CA, 94608-2916, US)
UNIVERSITY OF WASHINGTON (4311 Eleventh Avenue NE, Suite 500 Seattle, WA, 98105-4608, US)
Anderson, Neils H. (6529 Greenwood Avenue N, Seattle, WA, 98103, US)
Bowman, Jason (4810 Elm Street, Quincy, IL, 62305, US)
Erwin, Alice (Chiron Corporation, 4560 Horton Street Emeryville, CA, 94608, US)
Harwood, Eric (Chiron Corporation, 4560 Horton Street Emeryville, CA, 94608, US)
Kline, Toni (Chiron Corporation, 4560 Horton Street Emeryville, CA, 94608, US)
Mdluli, Khisimuzi (Chiron Corporation, 4560 Horton Street Emeryville, Ca, 94608, US)
Simon NG. (Chiron Corporation, 4560 Horton Street Emeryville, CA, 94608, US)
Pfister, Keith B. (Chiron Corporation, 4560 Horton Street Emeryville, CA, 94608, US)
Shawar, Ribhi (Chiron Corporation, 4560 Horton Street Emeryville, CA, 94608, US)
Wagman, Allan (Chiron Corporation, 4560 Horton Street Emeryville, CA, 94608, US)
Yabannavar, Asha (Chiron Corpoartion, 4560 Horton Street Emeryville, CA, 94608, US)
International Classes:
C07C233/83; C07C239/16; C07C251/40; C07C255/24; C07C255/25; C07C255/44; C07C255/57; C07C259/06; C07C275/14; C07C275/16; C07C275/26; C07C279/14; C07C311/06; C07C311/08; C07C311/19; C07C311/21; C07C317/32; C07C323/25; C07C323/41; C07C323/60; C07C323/62; C07C335/08; C07C337/08; C07C381/00; C07D207/08; C07D207/09; C07D207/14; C07D207/16; C07D207/27; C07D207/327; C07D211/26; C07D211/42; C07D211/56; C07D211/58; C07D211/62; C07D213/38; C07D213/40; C07D213/54; C07D213/56; C07D213/61; C07D213/74; C07D213/80; C07D213/81; C07D213/82; C07D215/48; C07D217/26; C07D231/12; C07D233/54; C07D235/14; C07D239/26; C07D239/42; C07D241/04; C07D241/12; C07D241/18; C07D263/34; C07D285/01; C07D295/13; C07D295/135; C07D295/155; C07D295/192; C07D295/215; C07D307/68; C07D311/24; C07D317/60; C07D317/68; C07D333/20; C07D333/24; C07D333/32; C07D333/36; C07D333/58; C07D453/00; C07D207/26; C07D207/32; C07D235/10; C07D285/00; (IPC1-7): A61K/
Domestic Patent References:
WO1997042179A11997-11-13
WO1998022494A21998-05-28
Other References:
T. HIGUCHI; V. STELLA: "Pro-drugs as Novel Delivery Systems", vol. 14, A.C.S. SYMPOSIUM SERIES
"Bioreversible Carriers in Drug Design", 1987, AMERICAN PHARMACEUTICAL ASSOCIATION AND PERGAMON PRESS
See also references of EP 1618087A4
Attorney, Agent or Firm:
Collier, Steven W. (Chiron Corporation, Intellectual Property R-338 P.O. Box 809, Emeryville CA, 94662-8097, US)
Download PDF:
Claims:
What is claimed is:
1. A compound according to the formula I: or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein E is absent or selected from the group consisting of (1) H, (2) substituted or unsubstituted ClC6alkyl, (3) substituted or unsubstituted C2C6alkenyl, (4) substituted or unsubstituted C2C6alkynyl, (5) substituted or unsubstituted aryl ; (6) substituted or unsubstituted heterocyclyl, and (7) substituted or unsubstituted heteroaryl; L is absent or selected from the group consisting of (1) substituted or unsubstituted ClC6alkyl, (2) (NH)01(CH2)jNR3L(CH2)k, <BR> <BR> <BR> (3) (NH)01C(R1L, R2L)NR3LC(R1L, R2L),<BR> (4) C(R1L, R2L)OC(R1L, R2L),<BR> <BR> <BR> <BR> <BR> <BR> (5) (CH2)jNR3LC(R1L, R2L)CONH(CH2)k,<BR> <BR> <BR> <BR> (6) COC(R1L, R2L)NHCO, (7)CONH, (8) NHCO, wherein RIL, R2L, and R3L are independently selected from the group consisting of (a) H, (b) substituted or unsubstituted ClC6alkyl, (c) ClC6alkyl substituted with aryl, (d) ClC6alkyl substituted with heterocyclyl, and (e) ClC6alkyl substituted with heteroaryl, or RIL and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 12 ring atoms of the heterocyclic ring system are selected from N, O and S, j is an integer of 04; k is an integer of 04; D is absent or selected from the group consisting of (1) substituted or unsubstituted C3Cscycloalkyl, (2) substituted or unsubstituted aryl, (3) substituted or unsubstituted heterocyclyl, and (4) substituted or unsubstituted heteroaryl ; G is absent or selected from the group consisting of (1) (CH2) iO(CH2)i, (2) (CH2) iS(CH2)i, (3) (CH2)iNRg(CH2)i (4) C(=O), (5) NHC(=O), <BR> <BR> <BR> <BR> <BR> <BR> (7) (CH2) iNHCH2C (=O) NH,<BR> <BR> <BR> <BR> <BR> (8)CC, (9) C#CC#C, and (10)C=C ; wherein Rg is H or substituted or unsubstituted ClC6alkyl ; i is an interger of 04; Y is selected from the group consisting of (1) substituted or unsubstituted C3C8cycloalkyl, (2) substituted or unsubstituted aryl, (3) substituted or unsubstituted heterocyclyl, and (4) substituted or unsubstituted heteroaryl ; X is selected from the group consisting of (1) (C=O), (2) C1C6alkyl(C=O), (3) C2C6alkenyl(C=O), (4)C2C6alkynyl(C=Ok and (5)CH2; or when B is absent, X and A, together with the atoms to which they are attached can form a heterocyclic ring, having from 5 to 8 ring atoms, wherein 12 ring atoms of the heterocyclic ring system are selected from N, O and S; B is a absent or wherein Rlb and Rab, are independently selected from the group consisting of (a) H, (b) substituted or unsubstituted ClC6alkyl, (c) substituted or unsubstituted C2C6alkenyl, (d) substituted or unsubstituted C2C6alkynyl, (e) substituted or unsubstituted aryl, (f) substituted or unsubstituted heterocyclyl, (g) substituted or unsubstituted heteroaryl, (h) ClC6alkyl substituted with aryl, (i) CIC6alkyl substituted with heterocyclyl, and (j) ClC6alkyl substituted with heteroaryl, or Rlb and R2b, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 12 ring atoms of the heterocyclic ring system are selected from N, O and S ; q is an integer of 04; R3 is H or substituted or unsubstituted ClC6alkyl, or R3 and A, together with the atoms to which they are attached can form a substituted or unsubstituted 310 membered cycloalkyl or a heterocyclic ring system, wherein the heterocyclic ring system may have from 3 to 10 ring atoms, with 1 to 2 rings being in the. ring system and contain from 14 heteroatoms selected from N, O and S; R4 is H or substituted or unsubstituted ClC6alkyl, or R4 and A, together with the atoms to which they are can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 12 ring atoms of the heterocyclic ring system are selected from N, O and S; n is an integer of 02; A is selected from the group consisting of (1) H, (2) (CH2)rC(R1a, R2a)(CH2)sOR3a, (3) (CH2)rC(R1a, R2a) N (R4a Wa), (4) (CH2)rC(R1a, R2a)N(R4a)COR3a, (5) (CH2)rC(R1a, R2a)NHCON(R4a, R5a), (6) (CH2)rC(R1a, R2a)NHC(=NH) N ( (7) CH(R1a, R2a), (8) C#CH, (9) (CH2)rC(R1a, R2a) CN, (10) (CH2) rC (Rla, R2a) C02R3a, and (11) (CH2)rC(R1a, R2a) CN (R4a R5a) wherein Rla, R2a, R3a, R4a, and R5a are independently selected from the group consisting of (a) H, (b) substituted or unsubstituted ClC6alkyl, (c) substituted or unsubstituted aryl, (d) substituted or unsubstituted heterocyclyl, (e) substituted or unsubstituted heteroaryl, (f) ClC6alkyl substituted with aryl, (g) ClC6alkyl substituted with heterocyclyl, and (h) ClC6alkyl substituted with heteroaryl, or Rla and R5a together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 12 ring atoms of the heterocyclic ring system are selected from N, O and S; r is an integer of 04 ; s is an integer of 04; Q is absent or selected from the group consisting of (1) C (=O) N (RI, R2), (2) NHC(=O)N(R1, R2), (3)N (OH) C (=O) N (R1, R2), (4) CH (OH) C (=O) N (R1, R2), (5)CH CH[N(R2q, R3q) C (=o) N (RI, R2), (6) CHR1qC(=O) N (Ri, R2), (7)C02H, (8) C(=O)NHSO2R4q, (9) SO2NH2, (10) N (OH) C (=O) RIq, (11) N(OH)SO2R4q, (12) NHSO2R4q, (13)SH, (14) CH (SH) (CH2) 01C(=O) N (Ri, R2), (15)CH (SH) (CH2) 01CO2H, (16) CH (OH) (CH2) 01CO2H, (17)CH (SH) CH2C02R (18) CH(OH) (CH2) SO2NH2, (19) CH (CH2SH) NHCOR (20)CH (CH2SH) NHSO2R4q, (21) CH(CH2SR5q)CO2H, (22) CH (CH2SH) NHSO2NH2, <BR> <BR> (23) CH (CH20H) CO2H,<BR> <BR> <BR> <BR> <BR> <BR> (24)CH (CH20H) NHS02NH2, (25) C (=O) CH2CO2H, (26)C (=O) (CH2) o1CONH2, (27) OSO2NHR5q, (28) SO2NHNH2, (29) P (=O) (OH) 2, N I (31)"N, and Rl is selected from the group consisting of (1) H, (2)OH, (3) OC16alkyl, (4) N(R2q,R3q), and (5) substituted or unsubstituted Cl 6alkyl ; R2 is selected from the group consisting of (1) H, (2) substituted or unsubstituted ClC6alkyl, (3) substituted or unsubstituted C2C6alkenyl, (4) substituted or unsubstituted C2C6alkenyl, (5) substituted or unsubstituted aryl, (6) substituted or unsubstituted heterocyclyl, (7) substituted or unsubstituted heteroaryl, (8) C1C8alkyl substituted with aryl, (9) ClC6alkyl substituted with heterocyclyl, and (10) ClC6alkyl substituted with heteroaryl, or Ri and Ra, together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 14 ring atoms of the heterocyclic ring system are selected from N, O and S, Rlq, R2q, R3q, R4q, and Rsq are selected from H or C1C6 alkyl, wherein B is absent, or E, L, G, and B are absent, or E, L, and G are absent, or E, L, and B are absent, or E, L, D, G, and B are absent.
2. A compound of claim 1, wherein wherein E is absent or selected from the group consisting of (1) H, (2) substituted or unsubstituted ClC6alkyl, (3) substituted or unsubstituted aryl, (4) substituted or unsubstituted heterocyclyl, and (5) substituted or unsubstituted heteroaryl; L is absent or selected from the group consisting of (1) (CH2) jNR3L(CH2)k (3) C(R1L,R2L)jOC(R1L,R2Lk), (4) (CH2)jNR3LC(R1L,R2L)kCONH(CH2)k, (5)COC (R1L, R2L)NHCO, (6) CONH, and (7)NHCO, wherein R1L, R2L, R3L are independently selected from the group consisting of (a) H, (b) substituted or unsubstituted CiC6alkyl, (c) Calkyl substituted with aryl, (d) ClC6alkyl substituted with heterocyclyl, (e) CIC6alkyl substituted with heteroaryl, or RIL and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 12 ring atoms of the heterocyclic ring system are selected from N, O and S; j is an integer of 04; k is an integer of 04; D is absent or selected from the group consisting of (1) substituted or unsubstituted C3C8cycloalkyl, (2) substituted or unsubstituted aryl, (3) substituted or unsubstituted heterocyclyl, (4) substituted or unsubstituted heteroaryl, and G is absent or selected from the group consisting of (1)C (=0), ) , (2) NHC(=O), (3) C (=O) NH, (4) (CH2)iNHCH2C(=O) NH, (5)CC, and (6)CCC=C, wherein i is an interger of 04; Y is selected from the group consisting of (1) substituted or unsubstituted C3Cscycloalkyl, (2) substituted or unsubstituted aryl, (3) substituted or unsubstituted heterocyclyl, and (4) substituted or unsubstituted heteroaryl; X is selected from the group consisting of (1) (C=O),<BR> <BR> <BR> <BR> <BR> (2)ClC6alkYl (C=O), (3) C2C6alkenyl(C=O), (4) C2C6alkynyl(C=O), and (5) CH2; or when B is absent, X and A, together with the atoms to which they are attached can form a heterocyclic ring, having from 5 to 8 ring atoms, wherein 12 ring atoms of the heterocyclic ring system are selected from N, O and S; B is absent or wherein Rlb and R2b are independently selected from the group consisting of (a) H (b) substituted or unsubstituted ClC6alkyl, (c) substituted or unsubstituted C2C6alkenyl, (d) substituted or unsubstituted C2C6alkenyl, (e) substituted or unsubstituted aryl, (f) substituted or unsubstituted heterocyclyl, (g) substituted or unsubstituted heteroaryl, (h) ClC6alkyl substituted with aryl, (i) ClC6alkyl substituted with heterocyclyl, and (j) ClC6alkyl substituted with heteroaryl, or Rlb and R2b, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 12 ring atoms of the heterocyclic ring system are selected from N, O and S; q is an integer of 02; R3 is H or substituted or unsubstituted ClC6alkyl, or R3 and A, together with the atoms to which they are attached can form a substituted or unsubstituted 310 membered cycloalkyl or a heterocyclic ring system, wherein the heterocyclic ring system may have from 3 to 10 ring atoms, with 1 to 2 rings being in the ring system and contain from 14 heteroatoms selected from N, O and S; R4 is H or substituted or unsubstituted ClC6alkyl, or R4 and A, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 12 ring atoms of the heterocyclic ring system are selected from N, O and S; A is selected from the group consisting of (1) H, (2) (CH2)rC(R1a,R2a)(CH2)sOR3a, (3) (CH2)RC(R1a,R2a)N(R4a,R5a), (4) (CH2)rC(R1a,R2a) N (R4a) COR3a, (5) (CH2)rC(R1a,R2a)NHCON(R4a,R5a), (6) (CH2) rC (R1a,R2a)NHC(=NH) N (R4a Ra), (7) CH(R1a,R2a), (8) C#CH, (9) (CH2) rC (R1a,R2a)CN, and (10) (CH2)rC(R1a,R2a)CO2R3a, wherein Rla, R2a, R3a, R4a, and R5a, are independently selected from the group consisting of (a) H, (b) substituted or unsubstituted ClC6alkyl, (c) ClC6alkyl substituted with aryl, (d) ClC6alkyl substituted with heterocyclyl, and (e) ClC6alkyl substituted with heteroaryl, or R4a and R5a, together with the N atom to which they. are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 12 ring atoms of the heterocyclic ring system are selected from N, O and S; r is an integer of 04 ; Q is absent or selected from the group consisting of (1)C (=O) N (RI, R2), (2)NHC (=O) N (Ri, R2), (3) N(OH) C (=O) N (RI, R2), (4)CH (OH) C (=O) N (RI, R2), (5) CN[N(R2q,R3q) C (=O) N (R1, R2) and (6)CHRIqC (=O) N (R1, R2), Ri is selected from the group consisting of (1) H, (2) OH, (3) OCi6alkyl, (4) N (R2q, R3q), and (5) substituted or unsubstituted Cl 6alkyl ; R2 is selected from the group consisting of (1) H, (2) substituted or unsubstituted ClC6alkyl, (3) substituted or unsubstituted aryl, (4) substituted or unsubstituted heterocyclyl, (5) substituted or unsubstituted heteroaryl, (6) ClC6alkyl substituted with aryl, (7) ClC6alkyl substituted with heterocyclyl, and (8) ClC6alkyl substituted with heteroaryl, or R1andR2, together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 14 ring atoms of the heterocyclic ring system are selected from N, O and S, Rlq, R2q, and R3q are selected from H or ClC6 alkyl, wherein B is absent, or E, L, G, and B are absent, or E, L, and G are absent, or E, L, and B are absent, or E, L, D, G, and B are absent.
3. A compound of claim 1, having the formula II: a or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein DGY taken together, is selected from the group consisting of wherein R is selected from the group consisting ofCH3,C2H5,CH20H,OH,OCH3,OC2Hs, OCF3, CN, NO2, CO2H, CO2CH3, CONH2, NH2, F, C1, Br, C3F, N(CH3)W, NHSO2CH3, andNHCOCH3 ; X is selected from the group consisting of (1)(ccok (2) C1C6alkyl(C=O), and (2)C2C6alkenyl (C=O).
4. A compound of claim I, having the formular HI : or a stereoisomer, pharmaceutically salt, ester, or prodrug thereof, wherein DGY taken together, is selected from the group consisting of wherein R is selected from the group consisting ofCH3,C2Hs,CH20H,OH,OCH3,OC2Hs, OCF3, CN, NO2, CO2H, CO2CH3, CONH2, NH2, F, Cl, Br, CF3, N(CH3)2, NHSO2CH3, andNHCOCH3 ; X is selected from the groups consisting of (1) (C=O), (2) C1C6alkyl(C=O), and (3)C2C6alkenyl (C=O).
5. A compound of claim 1, having the formula IV: or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein DGY taken together, is selected from the group consisting of wherein R is selected from the group consisting of CH3, C2H5, CH2OH, OH, OCH3, OC2H5, OCF3, CN, NO2, CO2H, CO2CH3, CONH2, NH2, F, Cl, Br, CF3, N(CH3)2, NHSO2CH3, andNHCOCH3 ; X is selected from the groups consisting of (1) (C=O), (2) C1C6alkyl(C=O), and (3)C2C6alkenyl (C=O).
6. A compound of claim 1, having the formula V: or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein DGY taken together, is selected from the group consisting of wherein R is selected from the group consisting of CH3, C2H5, CH2OH, OH, OCH3, OC2H5, OCF3, CN, NO2, CO2H, CO2CH3, CONH2, NH2, F, Cl, Br, CF3, N(CH3)2, NHSO2CH3, andNHCOCH3 ; X is selected from the group consisting of (1) (C=O), (2) C1C6alkyl(C=O), and (3)C2C6alkenyl (C=O).
7. A compound of claim 1, having the formula VI: or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein E is absent or selected from the group consisting of (1) H, (2) substituted or unsubstituted CiC6alkyl, (3) substituted or unsubstituted aryl, (4) substituted or unsubstituted heterocyclyl, and (5) substituted or unsubstituted heteroaryl, or E and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 14 ring atoms of the heterocyclic ring system are selected from N, O and S, R1L, R3L are independently selected from the group consisting of (1) H, (2) substituted or unsubstituted ClC6alkyl, (3) ClC6alkyl substituted with aryl, (4) ClC6alkyl substituted with heterocyclyl, and (5) ClC6alkyl substituted with heteroaryl, or RIL and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 12 ring atoms of the heterocyclic ring system are selected from N, O and S.
8. A compound of claim 1, having the formula VII: VII or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein E is absent or selected from the group consisting of (1) H, (2) substituted or unsubstituted ClC6alkyl, (3) substituted or unsubstituted aryl, (4) substituted or unsubstituted heterocyclyl, and (5) substituted or unsubstituted heteroaryl, or E and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 14 ring atoms of the heterocyclic ring system are selected from N, O and S ; RIL, R3L are independently selected from the group consisting of (1) H, (2) substituted or unsubstituted C1C6alkyl, (3) ClC6alkyl substituted with aryl, (4) ClC6alkyl substituted with heterocyclyl, and (5) Calkyl substituted with heteroaryl, or RIL and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 12 ring atoms of the heterocyclic ring system are selected from N, O and S.
9. A compound of claim 1, having the formula VHI : VIII or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein E is absent or selected from the group consisting of (1) H, (2) substituted or unsubstituted ClC6alkyl, (3) substituted or unsubstituted aryl, r (4) substituted or unsubstituted heterocyclyl, and (5) substituted or unsubstituted heteroaryl, or E and R3L, together with the atoms to which they are can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 14 ring atoms of the heterocyclic ring system are selected from N, O and S; RtL, R3L are independently selected from the group consisting of (1) H, (2) substituted or unsubstituted ClC6alkyl, (3) ClC6alkyl substituted with aryl, (4) ClC6alkyl substituted with heterocyclyl, and (5) ClC6alkyl substituted with heteroaryl, or R9L and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 12 ring atoms of the heterocyclic ring system are selected from N, O and S.
10. A compound of claim 1, having the formula IX: IX or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein E is absent or selected from the group consisting of (1) H, (2) substituted or unsubstituted ClC6alkyl, (3) substituted or unsubstituted aryl, (4) substituted or unsubstituted heterocyclyl, and (5) substituted or unsubstituted heteroaryl, or E and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 14 ring atoms of the heterocyclic ring system are selected from N, O and S; RIL, R3L are independently selected from the group consisting of (1) H, (2) substituted or unsubstituted C1C6alkyl, (3) ClC6alkyl substituted with aryl, (4) ClC6alkyl substituted with heterocyclyl, and (5) ClC6alkyl substituted with heteroaryl, or RIL and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 12 ring atoms of the heterocyclic ring system are selected from N, O and S.
11. A compound of claim 1, having the formula X: X or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein E is absent or selected from the group consisting of (1) H, (2) substituted or unsubstituted C1C6alkyl, (3) substituted or unsubstituted aryl, (4) substituted or unsubstituted heterocyclyl, and (5) substituted or unsubstituted heteroaryl, or E and altogether with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 14 ring atoms of the heterocyclic ring system are selected from N, O and S; RIL, R3L are independently selected from the group consisting of (1) H, (2) substituted or unsubstituted ClC6alkyl, (3) ClC6alkyl substituted with aryl, (4) ClC6alkyl substituted with heterocyclyl, and (5) ClC6alkyl substituted with heteroaryl, or RIL and R3L, together with the atoms to which they are can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 12 ring atoms of the heterocyclic ring system are selected from N, O and S.
12. A compound of claim 1, having the formula XI: or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein YX taken together, is selected from the group consisting of.
13. A compound of claim 1, having the formula XII : or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein Rlb and R2b are independently selected from the group consisting of (1) H, (2) substituted or unsubstituted ClC6alkyl, (3) substituted or unsubstituted C2C6alkenyl, (4) substituted or unsubstituted C2C6alkenyl, (5) substituted or unsubstituted aryl, (6) substituted or unsubstituted heterocyclyl, (7) substituted or unsubstituted heteroaryl, (8) ClC6alkyl substituted with aryl, (9) ClC6alkyl substituted with heterocyclyl, and (10) ClC6alkyl substituted with heteroaryl ; q is an integer of 02;.
14. A compound of claim 1, having the formula XIII : XIII or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein R4 is selected from the group consisting of (1). H, (2) substituted or unsubstituted ClC6alkyl, (3) ClC6alkyl substituted with aryl, (4) ClC6alkyl substituted with heterocyclyl, and (5) ClC6alkyl substituted with heteroaryl; A is H orCH (CH3) OH ; Rl is H or substituted or unsubstituted C16alkyl ; R2 is selected from the group consisting of (1) H, (2) substituted or unsubstituted CiC6alkyl, (3) substituted or unsubstituted aryl, (4) substituted or unsubstituted heterocyclyl, (5) substituted or unsubstituted heteroaryl, (6) ClC6alkyl substituted with aryl, (7) ClC6alkyl substituted with heterocyclyl, (8) ClC6alkyl substituted with heteroaryl, or Rl and R2together withthe N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 12 ring atoms of the heterocyclic ring system are selected from N, O and S.
15. A compound of claim 1, having the formula XIV: or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein DGY taken together is selected from the group consisting of wherein R is selected from the group consisting of CH3, C2H5, CH2OH, OH, OCH3, OC2H5, OCF3,CN,NO2,CO2H,C02CH3,CONH2,NH2,F,Cl,Br,CF3,N (CH3) 2, NHSO2CH3, andNHCOCH3 ; R4 is selected from the group consisting of (1) H, (2) substituted or unsubstituted C1C6alkyl, (3) ClC6alkyl substituted with aryl, (4) ClC6alkyl substituted with heterocyclyl, and (5) ClC6alkyl substituted with heteroaryl.
16. A compound of claim 1, having the formula XV: or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein DGY taken together, is selected from the group consisting of wherein R is selected from the group consisting ofCH3,C2Hs,CH2OH,OH,OCH3,OC2H5,.
17. OCF3,CN,NO2,CO2H,C02CH3,CONH2,NH2,F,Cl,Br,CF3,N (CH3) 2, nhso2ch3, andNHCOCH3 ;.
18. A compound of claim 1, having the formula XVI: or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein DGY taken together, is selected from the group consisting of wherein R is selected from the group consisting ofCH3,C2H5,CH20H,OH,OCH3,OC2Hs, OCF3,CN,NO2,C02H,C02CH3,CONH2,NHz,F,Cl,Br,CF3,N (CH3) 2, NHSO2CH3, andNHCOCH3 ; R4 is selected from the group consisting of (1) H, (2) substituted or unsubstituted C1C6alkyl, (3) ClC6alkyl substituted with aryl, (4) C1C6alkyl substituted with heterocyclyl, and (5) ClC6alkyl substituted with heteroaryl;.
19. A compound of claim 1, having the formula XVII : XVII or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein DGY taken together, is selected from the group consisting of wherein R is selected from the group consisting ofCH3,C2H5,CH20H,OH,OCH3,OC2H5, <BR> <BR> <BR> OCF3,CN ; N02,CO2H,C02CH3,CONH2,NH2,F,Cl,Br,CF3,N (CH3) 2,NHS02CH3,<BR> <BR> <BR> <BR> <BR> <BR> andNHCOCH3.
20. A pharmaceutical composition comprising a compound from one of claims 118 and a pharmaceutically acceptable excipient.
21. A pharmaceutical composition comprising a compound from one of claims 118, a second agent, and a pharmaceutically acceptable excipient.
22. A method of treating a patient comprising administering to a patient in need thereof, an effective amount of a compound from one of claims 118.
23. A method of treating a patient comprising administering to a patient in need thereof, an effective amount of a compound from one of claims 118 and an effective amount of a second agent.
24. A method of treating an infection comprising administering to a patient in need thereof, an effective amount of a compound from one of claims 118.
25. A method of treating an infection comprising administering to a patient in need thereof, an effective amount of a compound from one of claims 118 and an effective amount of a second agent.
Description:
ANTIBACTERIAL AGENTS This application claims benefit of priority to the following US Provisional Patent Applications, serial no. 60/438,523, filed January 8,2003 ; serial no. 60/466,974, filed April 30,2003 ; and serial no.

60/520,211 filed November 13,2003 ; each of which is incorporated herein by reference in its entirety for any purpose.

FIELD OF THE INVENTION This invention pertains generally to treating infections caused by gram-negative bacteria. More specifically, the invention described herein pertains to treating gram-negative infections by inhibiting activity of UDP-3-0- (R-3-hydroxydecanoyl)-N-acetylglucosamine deacetylase (LpxC). The present invention provides small molecule inhibitors of LpxC, pharmaceutical formulations containing such inhibitors, methods of treating patients with such pharmaceutical formulations, and to methods of preparing such pharmaceutical formulations and inhibitors. The inhibitors can be used to treat Gram- negative infections of patients alone and in combination with other antibacterials.

BACKGROUND OF THE INVENTION Over the past several decades, the frequency of antimicrobial resistance and its association with serious infectious diseases have increased at alarming rates. The increasing prevalence of resistance among nosocomial pathogens is particularly disconcerting. Of the over 2 million nosocomial infections occurring each year in the United States, 50 to 60% are caused by antimicrobial-resistant strains of bacteria. This high rate of resistance increases the morbidity, mortality, and costs associated with nosocomial infections. In the United States, nosocomial infections are thought to contribute to or cause more than 77,000 deaths per year and cost approximately $5 to $10 billion annually. Among Gram-positive organisms, the most important resistant pathogens are methicillin- (oxacillin-) resistant Staphylococcus aureus, B-lactam-resistant and multidrug-resistant pneumococci, and vancomycin- resistant enterococci. Important causes of Gram-negative resistance include extended-spectrum B- lactamases (ESBLs) in Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis, high-level third-generation cephalosporin (Amp C) B-lactamase resistance among Enterobacter species and Citrobacter freundii, and multidrug-resistance genes observed in Pseudomonas aeruginosa, Acinetobacter, and Stenotrophomonas maltophilia. (Jones RN 2001 Chest 119 (supplement), 397S- 404S : Resistance patterns among nosocomial pathogens: Trends over the past few years.) The problem of antibacterial resistance is compounded by the existence of bacterial strains resistant to multiple antibacterials. For example, Pseudomonas aeruginosa isolates resistant to fluoroquinolones are virtually all resistant to additional antibacterials (Sahm DF et al 2001 Antimicrobial Agents and Chemotherapy 45,267-274 : Evaluation of current activities of fluoroquinolones against gram-negative bacilli using centralized in vitro testing and electronic surveillance.) Thus there is a need for new antibacterials, particularly antibacterials with novel mechanisms of action. Most of the antibacterial discovery effort in the pharmaceutical industry is aimed at development of drugs effective against gram-positive bacteria. However, there is also a need for new gram-negative antibacterials. Gram-negative bacteria are in general more resistant to a large number of antibacterials and chemotherapeutic agents than are gram-positive bacteria. A survey of recently reported antibacterials of natural origin showed that over 90% lacked activity against Escherichia coli, although they were active against gram-positive bacteria. The outer membrane of gram-negative bacteria contributes to this intrinsic resistance by acting as an efficient permeability barrier, because the narrow porin channels limit the penetration of hydrophilic solutes and the low fluidity of the lipopolysaccharide leaflet slows down the inward diffusion of lipophilic solutes. A second mechanism contributes to the intrinsic resistance of gram-negative bacteria. Recent studies showed that multiple drug efflux pumps, sometimes with unusually broad specificity, act as this second factor to create the general intrinsic resistance of gram-negative bacteria. When their expression levels are elevated as a consequence of physiological regulation or genetic alteration, they can frequently produce impressive levels of resistance to a wide variety of antimicrobial agents. (Nikaido H 1998 Clinical Infectious Diseases 27 (Suppl 1), S32-41: Antibacterial resistance caused by gram-negative multidrug efflux pumps.) Historically, most development of antimicrobial agents has been relatively empirical. Active compounds have generally been found via screening soil, sewage, water, and other natural substances to detect antimicrobial-producing organisms, or by screening various chemical compounds. Once a leading candidate has been found and its chemical structure determined, a series of analogs is made to identify an optimal compound for further clinical development. A more rational approach involves the defining of new targets, such as genes or enzymatic functions, responsible for a crucial cellular essential activity. Once this has been done, inhibitors or blockers of the function or gene product can be developed.

In order to identify potential targets for novel gram-negative antibacterial agents, studies aimed at identifying all essential and important genes in Pseudomonas aeruginosa have been performed.

Among the essential genes identified was lpxC, that encodes the enzyme uridyldiphospho-3-0- (R- hydroxydecanoyl)-N-acetylglucosamine deacetylase (LpxC). This enzyme is the first committed step in the synthesis of lipid A, the lipid moiety of lipopolysaccharide, that is an essential component of all gram-negative bacteria. It therefore is an attractive target for novel antibacterials. In order to be useful as antibacterial agents, LpxC inhibitors would not only have to inhibit the enzymatic activity of LpxC from a variety of bacteria, but would have to defeat the intrinsic resistance mechanisms of gram- negative bacteria, as described above: they would have to penetrate the outer membrane and be relatively unsusceptible to multidrug efflux pumps.

Researchers have identified a few compounds with antibacterial activity that target lipid A biosynthesis. WO 97/42179 to Patchett et al. discloses compounds of the formula: The compounds possess activity against certain gram-negative organisms, for example Escherichia coli, but are not active against other medically important gram-negative bacteria, for example Pseudomonas aeruginosa. Subsequent studies have found that the primary reason for their inactivity against particular, medically important gram-negative bacteria is their poor ability to inhibit P. aeruginosa LpxC; efflux by the major multidrug efflux pump or inability to penetrate the outer membrane were not the critical factors.

Jackman et al. , in J. Biol. Chem. (vol. 275, no. 15, April 14,2000, pps. 11002-11009), discuss the mechanism of lipid A biosynthesis in the context of gram-negative bacteria and discloses a new class ofhydroxamate-containing inhibitors of LpxC. Wyckoff et al. , in Trends in Microbiology (vol.

6, no. 4, April 1998, pps. 154-159), discuss the role of LpxC in lipid A biosynthesis and its role in regulation. Wyckoff et al. disclose a few oxazoline hydroxamic acids that inhibit bacterial growth.

However, Wyckoff et al. also discuss the shortcomings of the available deacetylase inhibitors as bactericidal agents against Pseudomonas and that more work is needed to be done in the area.

Thus, an increasing need exists for LpxC inhibitors that have activity as bactericidal agents against gram-negative bacteria. It is, accordingly, an object, of this invention to provide compounds and combinations of such compounds for use in the preparation of antibacterials and other pharmaceuticals capable of inhibiting Gram-negative bacterial infections.

U. S. Patent Publication No. 2001/0053555 (U. S. Patent Application Serial No. 08/958,638) published December 20, 2001, corresponding to WO 98/18754 published May 7,1998 discloses a combinatorial library of hydroxylamine, hydroxamic acid, hydroxyurea and hydroxylsulfonamide compounds purported to be potentially useful as inhibitors of metalloproteases. U. S. Patent No.

6,281, 245, a continuation in part of U. S. 08/958, 638 claims a method of inhibiting a deformylase enzyme by administering one of the hydroxylamine compounds from the combinatorial library as disclosed in U. S. Patent Publication No. 2001/0053555 and the corresponding WO 98/18754. Related to the above disclosed patent publications is WO 99/57097, published November 11,1999, that discloses a method of solid phase synthesis of the hydroxylamine library of compounds. WO 00/61134 (to British Biotech Pharmaceuticals Limited), published October 19,2000, discloses compounds of the formula below : The compounds are useful as antimicrobial agents that are believed to have bactericidal activity at least in part to intracellular inhibition of bacterial polypeptide deformylase.

In an earlier to British Biotech Pharmaceuticals Limited, WO 99/39704, published August 12, 1999, compounds of the formula below are disclosed : The compounds are useful as antimicrobial agents useful against gram-negative and gram positive bacteria.

Recently, De Novo Pharmaceuticals LTD disclosed in WO 02/50081, published June 27, 2002, antibacterial and antiprotozoal agents having the formulae shown below: The patent publication discusses that the antibacterial activity is due, at least in part, to intracellular inhibition of bacterial polypeptide deformylase.

SUMMARY OF THE INVENTION The present invention provides novel compounds, pharmaceutical formulations including the compounds, methods of inhibiting UDP-3-O-(R-3-hydroxydecanoyl)-N-acetylglucosamine deacetylase (LpxC), and methods of treating gram-negative bacterial infections.

In one embodiment, the present invention provides compounds of formula I : I or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein E is absent or selected from the group consisting of (1) H, (2) substituted or unsubstituted Cl-C6-alkyl, (3) substituted or unsubstituted C2-C6-alkenyl, (4) substituted or unsubstituted C2-C6-alkynyl, (5) substituted or unsubstituted aryl, (6) substituted or unsubstituted heterocyclyl, and (7) substituted or unsubstituted heteroaryl ; L is absent or selected from the group consisting of (1) substituted or unsubstituted Cl-C6-alkyl, (2) -(NH)0-1-(CH2)j-NR3L-(CH2)k-, (3) -(NH)0-1-C(R1L,R2L)-NR3L-C(R1L,R2L)-, <BR> <BR> <BR> (4) -C(R1L,R2L)-O-C(R1L,R2L)-,<BR> (5) -(CH2)j-NR3L-C(R1L,2RL)-CONH-(CH2)k-,<BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> (6)-CO-C (R1L, RzL)-NHCO-,<BR> <BR> <BR> <BR> <BR> (7)-CONH-,<BR> <BR> <BR> <BR> <BR> (8)-NHCO-, wherein R1L, R2L, and R3L are independently selected from the group consisting of (a) H, (b) substituted or unsubstituted CI-C6-alkyl, (c) Cl-C6-alkyl substituted with aryl, (d) Cl-C6-alkyl substituted with heterocyclyl, and (e) Cl-C6-alkyl substituted with heteroaryl, or RIL and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S; j is an integer of 0-4 ; k is an integer of 0-4; D is absent or selected from the group consisting of (1) substituted or unsubstituted C3-C8-cycloalkyl, (2) substituted or unsubstituted aryl, (3) substituted or unsubstituted heterocyclyl, and (4) substituted or unsubstituted heteroaryl; G is absent or selected from the group consisting of (1)- (CH2) i-O- (CH2) ;-, (2) -(CH2)i-S-(CH2)i-, (3) -(CH2)i-NRg-(CH2)i-, (4) -C (=O)-, (5) -NHC(=O)-, (6) -C(=O)NH-, (7)- (CH2) iNHCH2C (=O) NH-, (8)--C-C-, (9) -C#C-C#C-, and (10)-C=C- ; wherein Rg is H or substituted or unsubstituted Cl-C6-alkyl ; i is an interger of 0-4; Y is selected from the group consisting of (1) substituted or unsubstituted C3-C8-cycloalkyl, (2) substituted or unsubstituted aryl, (3) substituted or unsubstituted heterocyclyl, and (4) substituted or unsubstituted heteroaryl; X is selected from the group consisting of (1)- (C=O)-, (2) -C1-C6-alkyl-(C=O)-, (3)-C2-C6-alkenyl4C=O)-, (4)-C2-C6-alkynyl- (C=O)-, and (5) -CH2-; or when B is absent, X and A, together with the atoms to which they are attached can form a heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S; B is a absent or wherein Rlb and R2b, are independently selected from the group consisting of (a) H, (b) substituted or unsubstituted Cl-C6-alkyl, (c) substituted or unsubstituted C2-C6-alkenyl, (d) substituted or unsubstituted C2-C6-alkynyl, (e) substituted or unsubstituted aryl, (f) substituted or unsubstituted heterocyclyl, (g) substituted or unsubstituted heteroaryl, (h) Cl-C6-alkyl substituted with aryl, (i) Cl-C6-alkyl substituted with heterocyclyl, and (j) C1-C6-alkyl substituted with heteroaryl, or Rlb and R2b, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S; q is an integer of 0-4; R3 is H or substituted or unsubstituted Cl-C6-alkyl, or R3 and A, together with the atoms to which they are attached can form a substituted or unsubstituted 3-10 membered cycloalkyl or a heterocyclic ring system, wherein the heterocyclic ring system may have from 3 to 10 ring atoms, with 1 to 2 rings being in the ring system and contain from 1-4 heteroatoms selected from N, O and S; R4 is H or substituted or unsubstituted C1-C6-alkyl, or R4 and A, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S; n is an integer of 0-6; A is selected from the group consisting of (1) H, (a) -(CH2) rC (R1a, R2a) (CH2) sOR3A, (3) -(CH2)rC(R1a,2Ra) N (R4a Rsa) (4)- (CH2) rC (Rla, R2a) N (R4a) COR3a, (5) - (CH2) rC (R1a,R2a)NHCON(R4a,R5a), (6) -(CH2)rC(R1a,R2a)NHC(=NH)N(R4a,R5a), (7) -CH(R1a,R2a), (8) -C#CH, (9) dCH2) rC (R, R) CN, (10)- (CH2) rC (Rla, R2a) CO2R3a, and (11)- (CH2) rC (R1a,R2a) CON (R4a, R5a), wherein R1a, R2a, R3a, R4a, and Rusa are independently selected from the group consisting of (a) H, (b) substituted or unsubstituted C1-C6-alkyl, (c) substituted or unsubstituted aryl, (d) substituted or unsubstituted heterocyclyl, (e) substituted or unsubstituted heteroaryl, (f) Cl-C6-alkyl substituted with aryl, (g) Cl-C6-alkyl substituted with, heterocyclyl, and (h) Cl-C6-alkyl substituted with heteroaryl, or R4a and R5a together withthe N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S; r is an integer of 0-4; s is an integer of 0-4; Q is absent or selected from the group consisting of (1) -C (=O) N (R1, R2), (2) -NHC (=O) N (RI, R2), (3)-N (OH) C (=O) N (Ri, R2), (4) -CH (OH) C (=O) N (RI, R2), (5) -CH[N(R2q,R3q)]C(=O) N (R1, R2), (6)-CHRIqC (=O) N (Ri, R2), (7)-CO2H, <BR> <BR> <BR> (8) -C (=O) NHSO2R4q,<BR> <BR> <BR> <BR> <BR> <BR> <BR> (9)-SO2NH2,.

(10) -N(OH)C(=O)R1q, (11) -N(OH)SO2R4q, (12) -NHSO2R4q, (13)-SH, (14) -CH (SH) (CH2) 01C (=O) N (R1, R2), (15) -CH (SH) (CH2) 0-1CO2H, (16)-CH (OH) (CH2) o-tC02H, (17) -CH (SH) CH2C02R (18) -CH (OH) (CH2) SO2NH2, (19) -CH(CH2SH)NHCOR1q, <BR> <BR> <BR> (20) -CH (CH2SH) NHSO2R4q,<BR> <BR> <BR> <BR> <BR> <BR> (21) -CH (CH2SR5q) C02H, (22) -CH (CH2SH) NHS02NH2, <BR> <BR> <BR> <BR> (23) -CH (CH20H) CO2H,<BR> <BR> <BR> <BR> <BR> (24)-CH (CH20H) NHS02NH2, (25) -C(=O)CH2CO2H, (26) -C (=O) (CH2) o-iCONH2, (27) -OSO2NHR5q, (28)-SO2NHNH2, (29)-P (=O) (OH) 2, wherein R1 is selected-from the group consisting of (1) H, (2)-OH, (3) -OC1-6-alkyl, (4) -N(R2q,R3q), and (5) substituted or unsubstituted C1. 6-alkyl; R2 is selected from the group consisting of (1) H, (2) substituted or unsubstituted Cl-C6-alkyl, (3) substituted or unsubstituted C2-C6-alkenyl, (4) substituted or unsubstituted C2-C6-alkenyl, (5) substituted or unsubstituted aryl, (6) substituted or unsubstituted heterocyclyl, (7) substituted or unsubstituted heteroaryl, (8) Ci-C6-alkyl substituted with aryl, (9) Cl-C6-alkyl substituted with heterocyclyl, and (10) Cl-C6-alkyl substituted with heteroaryl, or Rl andR2, together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S, or R2 andR4, together with the N atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S; Rlq, R2q, R3q, R4q, and R5q are selected from H or Cl-C6 alkyl, wherein B is absent, or E, L, G, and B are absent, or E, L, and G are absent, or E, L, and B are absent, or E, L, D, G, and B are absent.

In one aspect, the invention provides a method of inhibiting a deacetylase enzyme in a gram- negative bacteria, thereby affecting bacterial growth, comprising administering to a patient in need of such inhibition a compound of formula I.

In another aspect, the invention provides a method of inhibiting LpxC, thereby modulating the virulence of a bacterial infection, comprising administering to a patient in need of such inhibition a compound of formula I.

In another aspect, the invention provides a method for treating a subject with a gram-negative bacterial infection comprising administering to the subject in need thereof an antibacterially effective amount of a compound of formula I with a pharmaceutically acceptable carrier. In a preferred embodiment of the method of treatment, the subject is a mammal and in some embodiments, a human.

In another aspect, the invention provides a method of administering an inhibitory amount of a compound of formula I to fermentative or non-fermentative gram-negative bacteria. In a preferred embodiment of the method of administering an inhibitory amount of a compound of formula I to fermentative or non-fermentative gram-negative bacteria, the gram-negative bacteria are selected from the group consisting of Pseudomonas aeruginosa, Stenotrophomonas maltophila, Burkholderia cepacia, Alcaligenes xylosoxidans, Acinetobacter, Enterobacteriaceae, Haemophilus, and Neisseria species.

In another embodiment, the invention provides a method of administering an inhibitory amount of a compound of formula I to gram-negative bacteria, such as Enterobacteriaceae which is selected from the group consisting of organisms such as Serratia, Proteus, Klebsiella, Enterobacter, Citrobacter, Salmonella, Providencia, Morganella, Cedecea, and Edwardsiella species and Escherichia coli.

Another embodiment of the invention provides a pharmaceutical composition comprising an effective amount of a compound of Formula I with a pharmaceutically acceptable carrier thereof.

Pharmaceutical formulations according to the present invention are provided which include any of the compounds described above in combination with a pharmaceutically acceptable carrier.

Another embodiment of the invention provides a method of co-administering the compound of formula I with other therapeutic agents that are selected for their particular usefulness against the condition that is being treated.

For example, the compound of formula I is useful in combination with other anti-bacterial agents. The compound of formula I augments the sensitivity of gram-negative bacteria to existing classes of antibacterials. Combinations of the presently disclosed compounds with other anti-bacterial agents are within the scope of the invention. Such anti-bacterial agents include, but are not limited to, erythromyciri, rifampicin, Nalidixic acid, carbenicillin, bacitracin, cycloserine, fosfomycin, and vancomycin.

DETAILED DESCRIPTION The present invention provides novel compounds, methods for inhibiting LpxC in gram- negative bacteria, and novel methods for treating bacterial infections. The compounds provided herein can be formulated into pharmaceutical formulations and medicaments that are useful in the methods of the invention. The invention also provides for the use of the compounds in preparing medicaments and pharmaceutical formulations, for use of the compounds in inhibiting LpxC, and for use of the compounds in treating bacterial infections in a subject.

The following abbreviations and definitions are used throughout this application: "LpxC"is an abbreviation that stands for UDP-3-0- (R-3-hydroxydecanoyl)-N- acetylglucosamine deacetylase.

Generally, reference to a certain element such as hydrogen or H is meant to include all isotopes of that element. For example, if an R group is defined to include hydrogen or H, it also includes deuterium and tritium.

The phrase "alkyl" refers to alkyl groups that do not contain heteroatoms. Thus the phrase includes straight chain alkyl groups such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl and the like. The phrase also includes branched chain isomers of straight chain alkyl groups, including but not limited to, the following that are provided by way of example:-CH (CH3) 2,-CH (CH3) (CH2CH3),-CH (CH2CH3) 2, - C (CH3) 3, -C (CH2CH3) 3, -CH2CH (CH3) 2,-CH2CH (CH3) (CH2CH3),-CH2CH (CH2CH3) 2, - CH2C (CH3) 3,-CH2C (CH2CH3) 3, -CH (CH3) CH (CH3) (CH2CH3),-CH2CH2CH (CH3) 2, -CH2CH2CH (CH3) (CH2CH3),-CH2CH2CH (CH2CH3) 2,-CH2CH2C (CH3) 3, -CH2CH2C (CH2CH3) 3, -CH (CH3) CH2CH (CH3) 2, -CH (CH3) CH (CH3) CH (CH3) 2, -CH (CH2CH3) CH (CH3) CH (CH3) (CH2CH3), and others. The phrase also includes cyclic alkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl and such rings substituted with straight and branched chain alkyl groups as defined above. Thus the phrase alkyl groups includes primary alkyl groups, secondary alkyl groups, and tertiary alkyl groups. Preferred alkyl groups include straight and branched chain alkyl groups and cyclic alkyl groups having 1 to 12 carbon atoms.

The phrase"substituted alkyl"refers to an alkyl group as defined above in which one or more bonds to a carbon (s) or hydrogen (s) are replaced by a bond to non-hydrogen and non-carbon atoms such as, but not limited to, a halogen atom such as F, Cl, Br, and I; an oxygen atom in groups such as hydroxyl groups, alkoxy groups, aryloxy groups, and ester groups; a sulfur atom in groups such as thiol groups, alkyl and aryl sulfide groups, sulfone groups, sulfonyl groups, and sulfoxide groups ; a nitrogen atom in groups such as amines, amides, alkylamines, dialkylamines, arylamines, alkylarylamines, diarylamines, N-oxides, imides, and enamines; a silicon atom in groups such as in trialkylsilyl groups, dialkylarylsilyl groups, alkyldiarylsilyl groups, and triarylsilyl groups; and other heteroatoms in various other groups. Substituted alkyl groups also include groups in which one or more bonds to a carbon (s) or hydrogen (s) atom is replaced by a higher-order bond (e. g., a double-or triple-bond) to a heteroatom such as oxygen in oxo, carbonyl, carboxyl, and ester groups; nitrogen in groups such as imines, oximes, hydrazones, and nitriles. Substituted alkyl groups further include alkyl groups in which one or more bonds to a carbon (s) or hydrogen (s) atoms is replaced by a bond to an aryl, heterocyclyl group, or cycloalkyl group. Preferred substituted alkyl groups include, among others, alkyl groups in which one or more bonds to a carbon or hydrogen atom is/are replaced by one or more bonds to fluorine atoms.

Another preferred substituted alkyl group is the trifluoromethyl group and other alkyl groups that contain the trifluoromethyl group. Other preferred substituted alkyl groups include those in which one or more bonds to a carbon or hydrogen atom is replaced by a bond to an oxygen atom such that the substituted alkyl group contains a hydroxyl, alkoxy, or aryloxy group. Still other preferred substituted alkyl groups include alkyl groups that have an amine, or a substituted or unsubstituted alkylamine, dialkylamine, arylamine, (alkyl) (aryl) amine, diarylamine, heterocyclylamine, diheterocyclylamine, (alkyl) (heterocyclyl) amine, or (aryl) (heterocyclyl) amine group.

The phrase"alkenyl"refers to straight and branched chain and cyclic groups such as those described with respect to alkyl groups as defined above, except that at least one double bond exists between two carbon atoms. Examples include, but are not limited to vinyl, -CH=C (H) (CH3),-CH=C (CH3) 2, -C (CH3) =C (H) 2,-C (CH3) =C (H) (CH3), -C (CH2CH3) =CH2, cyclohexenyl, cyclopentenyl, cyclohexadienyl, butadienyl, pentadienyl, and hexadienyl among others.

The phrase"substituted alkenyl"has the same meaning with respect to alkenyl groups that substituted alkyl groups had with respect to unsubstituted alkyl groups. A substituted alkenyl group includes alkenyl groups in which a non-carbon or non-hydrogen atom is bonded to a carbon double bonded to another carbon and those in which one of the non-carbon or non-hydrogen atoms is bonded to a carbon not involved in a double bond to another carbon.

The phrase"alkynyl"refers to straight and branched chain groups such as those described with respect to alkyl groups as defined above, except that at least one triple bond exists between two carbon atoms. Examples include, but are not limited to-C--C (H),-C_C (CH3),-C=C (CH2CH3), -C (H2) C-C (H), -C (H) 2C=C (CH3), and-C (H) 2C=C (CH2CH3) among others. The phrase"substituted alkynyl"has the same meaning with respect to alkynyl groups that substituted alkyl groups had with respect to unsubstituted alkyl groups. A substituted alkynyl group includes alkynyl groups in which a non-carbon or non-hydrogen atom is bonded to a carbon triple bonded to another carbon and those in which a non-carbon or non-hydrogen atom is bonded to a carbon not involved in a triple bond to another carbon.

The phrase"heterocyclyl"refers to both aromatic and nonaromatic ring compounds including monocyclic, bicyclic, and polycyclic ring compounds such as, but not limited to, quinuclidinyl, containing 3 or more ring members of which one or more is a heteroatom such as, but not limited to, N, O, and S. Although the phrase"unsubstituted heterocyclyl"includes condensed heterocyclic rings such as benzimidazolyl, it does not include heterocyclyl groups that have other groups such as alkyl or halo groups bonded to one of the ring members as compounds such as 2-methylbenzimidazolyl are substituted heterocyclyl groups. Examples of heterocyclyl groups include, but are not limited to: unsaturated 3 to 8 membered rings containing 1 to 4 nitrogen atoms such as, but not limited to pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, dihydropyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl (e. g. 4H-1, 2,4-triazolyl, lu-1, 2, 3-triazolyl, 2H-1, 2,3-triazolyl etc. ), tetrazolyl, (e. g. 1H- tetrazolyl, 2H tetrazolyl, etc. ); saturated 3 to 8 membered rings containing 1 to 4 nitrogen atoms such as, but not limited to, pyrrolidinyl, imidazolidinyl, piperidinyl, piperazinyl ; condensed unsaturated heterocyclic groups containing 1 to 4 nitrogen atoms such as, but not limited to, indolyl, isoindolyl, indolinyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl; unsaturated 3 to 8 membered rings containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms such as, but not limited to, oxazolyl, isoxazolyl, oxadiazolyl (e. g. 1,2, 4-oxadiazolyl, 1,3, 4-oxadiazolyl, 1,2, 5-oxadiazolyl, etc. ) ; saturated 3 to 8 membered rings containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms such as, but not limited to, morpholinyl; unsaturated condensed heterocyclic groups containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, for example, benzoxazolyl, benzoxadiazolyl, benzoxazinyl (e. g. 2H-1,4- benzoxazinyl etc. ) ; unsaturated 3 to 8 membered rings containing 1 to 3 sulfur atoms and 1 to 3 nitrogen atoms such as, but not limited to, thiazolyl, isothiazolyl, thiadiazolyl (e. g. 1,2, 3-thiadiazolyl, 1,2, 4-thiadiazolyl, 1,3, 4-thiadiazolyl, 1,2, 5-thiadiazolyl, etc. ) ; saturated 3 to 8 membered rings containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms such as, but not limited to, thiazolodinyl; saturated and unsaturated 3 to 8 membered rings containing 1 to 2 sulfur atoms such as, but not limited to, thienyl, dihydrodithiinyl, dihydrodithionyl, tetrahydrothiophene, tetrahydrothiopyran ; unsaturated condensed heterocyclic rings containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms such as, but not limited to, benzothiazolyl, benzothiadiazolyl, benzothiazinyl (e. g. 2H-1, 4-benzothiazinyl, etc.), dihydrobenzothiazinyl (e. g. 2H-3,4-dihydrobenzothiazinyl, etc. ), unsaturated 3 to 8 membered rings containing oxygen atoms such as, but not limited to furyl; unsaturated condensed heterocyclic rings containing 1 to 2 oxygen atoms such as benzodioxolyl (e. g. 1, 3-benzodioxoyl, etc. ); unsaturated 3 to 8 membered rings containing an oxygen atom and 1 to 2 sulfur atoms such as, but not limited to, dihydrooxathiinyl ; saturated 3 to 8 membered rings containing 1 to 2 oxygen atoms and 1 to 2 sulfur atoms such as 1, 4-oxathiane ; unsaturated condensed rings containing 1 to 2 sulfur atoms such as benzothienyl, benzodithiinyl; and unsaturated condensed heterocyclic rings containing an oxygen atom and 1 to 2 oxygen atoms such as benzoxathiinyl. Heterocyclyl group also include those described above in which one or more S atoms in the ring is double-bonded to one or two oxygen atoms (sulfoxides and sulfones). For example, heterocyclyl groups include tetrahydrothiophene,' tetrahydrothiophene oxide, and tetrahydrothiophene 1, 1-dioxide. Preferred heterocyclyl groups contain 5 or 6 ring members. More preferred heterocyclyl groups include morpholine, piperazine, piperidine, pyrrolidine, imidazole, pyrazole, 1,2, 3-triazole, 1,2, 4-triazole, tetrazole, thiomorpholine, thiomorpholine in which the S atom of the thiomorpholine is bonded to one or more O atoms, pyrrole, homopiperazine, oxazolidin-2-one, pyrrolidin-2-one, oxazole, quinuclidine, thiazole, isoxazole, furan, and tetrahydrofuran.

The phrase"substituted heterocyclyl"refers to a heterocyclyl group as defined above in which one of the ring members is bonded to a non-hydrogen atom such as described above with respect to substituted alkyl groups and substituted aryl groups. Examples, include, but are not limited to, 2- methylbenzimidazolyl, 5-methylbenzimidazolyl, 5-chlorobenzthiazolyl, 1-methyl piperazinyl, and 2- chloropyridyl among others.

The phrase"aryl"refers to aryl groups that do not contain heteroatoms. Thus the phrase includes, but is not limited to, groups such as phenyl, biphenyl, anthracenyl, naphtlienyl by way of example. Although the phrase"unsubstituted aryl"includes groups containing condensed rings such as naphthalene, it does not include aryl groups that have other groups such as alkyl or halo groups bonded to one of the ring members, as aryl groups such as tolyl are considered herein to be substituted aryl groups as described below. A preferred unsubstituted aryl group is phenyl. Unsubstituted aryl groups may be bonded to one or more carbon atom (s), oxygen atom (s), nitrogen atom (s), and/or sulfur atom (s) in the parent compound, however.

The phrase"substituted aryl group"has the same meaning with respect to unsubstituted aryl groups that substituted alkyl groups had with respect to unsubstituted alkyl groups. However, a substituted aryl group also includes aryl groups in which one of the aromatic carbons is bonded to one of the non-carbon or non-hydrogen atoms described above and also includes aryl groups in which one or more aromatic carbons of the aryl group is bonded to a substituted and/or unsubstituted alkyl, alkenyl, or alkynyl group as defined herein. This includes bonding arrangements in which two carbon atoms of an aryl group are bonded to two atoms of an alkyl, alkenyl, or alkynyl group to define a fused ring system (e. g. dihydronaphthyl or tetrahydronaphthyl). Thus, the phrase"substituted aryl"includes, but is not limited to tolyl, and hydroxyphenyl among others. Preferred substituents include straight and branched chain alkyl groups,-CH3,-C2H5,-CH2OH,-OH,-OCH3,-OC2H5,-OCF3,-CN,-N02,- C02H,-CO2CH3,-CONH2,-NH2,-F,-Cl, Br,-CF3,-N (CH3) 2,-NHS02CH3,-NHCOCH3.

The term"heteroaryl", as used herein, refers to a cyclic or bicyclic aromatic radical having from five to ten ring atoms in each ring of which one atom of the cyclic or bicyclic ring is selected from S, O and N; zero, one or two ring atoms are additional heteroatoms independently selected from S, 0 and N; and the remaining ring atoms are carbon, the radical being joined to the rest of the molecule via any of the ring atoms, such as, for example, pyridyl, pyrazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isooxazolyl, thiadiazolyl, oxadiazolyl, thiophenyl, furanyl, quinolinyl, isoquinolinyl, and naphthyridinyl, and the like.

The term"substituted heteroaryl"as used herein refers to a heteroaryl group as defined herein substituted by independent replacement of one, two or three of the hydrogen atoms thereon with Cl, Br, F, I, OH, CN, Cl-C3-alkyl, Cl-C6-alkoxy, Cl-C6-alkoxy substituted with aryl, haloalkyl, thioalkoxy, amino, alkylamino, dialkylamino, mercapto, nitro, carboxaldehyde, carboxy, alkoxycarbonyl and carboxamide. In addition, any one substituent may be an aryl, heteroaryl, or heterocycloalkyl group.

Preferred substituents include straight and branched chain alkyl groups,-CH3,-C2H5,-CH2OH,-OH,- OCH3,-OC2Hs,-OCF3,-CN,-N02,-C02H,-C02CH3,-CONH2,-NH2,-F,-Cl, Br,-CF3,-N (CH3) 2,- NHSO2CH3,-NHCOCH3.

The term"biaryl"refers to a group or substituent to which two aryl groups, which are not condensed to each other, are bound. Exemplary biaryl compounds include, for example, phenylbenzene, diphenyldiazene, 4-methylthio-1-phenylbenzene, phenoxybenzene, (2- phenylethynyl) benzene, diphenyl ketone, (4-phenylbuta-1, 3-diynyl) benzene, phenylbenzylamine, (phenylmethoxy) benzene, and the like. Preferred optionally substituted biaryl groups include: 2- (phenylamino)-N- [4- (2-phenylethynyl) phenyl] acetamide, 1,4-diphenylbenzene, N- [4- (2- phenylethynyl) phenyl]-2- [benzylamino] acetamide, 2-amino-N- [4- (2- phenylethynyl) phenyl] propanamide, 2-amino-N- [4- (2-phenylethynyl) phenyl] acetamide, 2- (cyclopropylamino)-N- [4- (2-phenylethynyl) phenyl] acetamide, 2- (ethylamino)-N- [4- (2- phenylethynyl) phenyl] acetamide, 2- [ (2-methylpropyl) amino]-N- [4- (2- phenylethynyl) phenyl] acetamide, 5-phenyl-2H-benzo [d] 1, 3-dioxolene, 2-chloro-l-methoxy4- phenylbenzene, 2- [ (imidazolylmethyl) amino]-N- [4- (2-phenylethynyl) phenyl] acetamide, 4-phenyl-1- phenoxybenzene, N- (2-aminoethyl) [4- (2-phenylethynyl) phenyl] carboxamide, 2-{[(4- fluorophenyl) methyl] amino}-N- [4- (2-phenylethynyl) phenyl] acetamide, 2-{[(4- methylphenyl) methyl] amino}-N- [4- (2-phenylethynyl) phenyl] acetamide, 4-phenyl-1- (trifluoromethyl) benzene, 1-butyl-4-phenylbenzene, 2- (cyclohexylamino)-N- [4- (2- phenylethynyl) phenyl] acetamide, 2- (ethylmethylamino)-N- [4- (2-phenylethynyl) phenyl] acetamide, 2- (butylamino)-N- [4- (2-phenylethynyl) phenyl] acetamide, N- [4- (2-phenylethynyl) phenyl]-2- (4- pyridylamino) acetamide, N- [4- (2-phenylethynyl) phenyl]-2- (quinuclidin-3-ylamino) acetamide, N- [4- (2-phenylethynyl) phenyl] pyrrolidin-2-ylcarboxamide, 2-amino-3-methyl-N- [4- (2- phenylethynyl) phenyl] butanamide, 4- (4-phenylbuta-1, 3-diynyl) phenylamine, 2- (dimethylamino)-N- [4- (4-phenylbuta-1, 3-diynyl) phenyl] acetamide, 2- (ethylamino)-N- [4- (4-phenylbuta-l, 3- diynyl) phenyl] acetamide, 4-ethyl-1-phenylbenzene, 1- [4- (2-phenylethynyl) phenyl] ethan-l-one, N- (1- carbamoyl-2-hydroxypropyl) [4- (4-phenylbuta-1, 3-diynyl) phenyl] carboxamide, N- [4- (2- phenylethynyl) phenyl] propanamide, 4-methoxyphenyl phenyl ketone, phenyl-N-benzamide, (tert- butoxy)-N- [ (4-phenylphenyl) methyl] carboxamide, 2- (3-phenylphenoxy) ethanehydroxamic acid, 3- phenylphenyl propanoate, 1- (4-ethoxyphenyl)-4-methoxybenzene, and [4- (2- phenylethynyl) phenyl] pyrrole.

The term"heteroarylaryl"refers to a biaryl group where one of the aryl groups is a heteroaryl group. Exemplary heteroarylaryl groups include, for example, 2-phenylpyridine, phenylpyrrole, 3- (2- phenylethynyl) pyridine, phenylpyrazole, 5-(2-phenylethynyl)-1, 3-dihydropyrimidine-2,4-dione, 4- phenyl-1, 2,3-thiadiazole, 2- (2-phenylethynyl) pyrazine, 2-phenylthiophene, phenylimidazole, 3- (2- piperazinylphenyl) furan, 3- (2, 4-dichlorophenyl) -4-methylpyrrole, and the like. Preferred optionally substituted heteroarylaryl groups include: 5-(2-phenylethynyl) pyrimidine-2-ylamine, 1-methoxy-4- (2- thienyl) benzene, l-methoxy-3-(2-thienyl) benzene, 5-methyl-2-phenylpyridine, 5-methyl-3- phenylisoxazole, 2- [3- (trifluoromethyl) phenyl] furan, 3-fluoro-5-(2-furyl)-2-methoxy-1-prop-2- enylbenzene, (hydroxyimino) (5-phenyl (2-thienyl)) methane, 5- [ (4-methylpiperazinyl) methyl]-2- phenylthiophene, 2- (4-ethylphenyl) thiophene, 4-methylthio-1- (2-thienyl) benzene, 2- (3- nitrophenyl) thiophene, (tert-butoxy)-N- [ (5-phenyl (3-pyridyl)) methyl] carboxamide, hydroxy-N- [ (5- phenyl (3-pyridyl) ) methyl] amide, 2- (phenyhnethylthio) pyridine, and benzylimidazole.

The term"heteroarylheteroaryl"refers to a biaryl group where both of the aryl groups is a . heteroaryl group. Exemplary heteroarylheteroaryl groups include, for example, 3-pyridylimidazole, 2- imidazolylpyrazine, and the like. Preferred optionally substituted heteroarylheteroaryl groups include: 2- (4-piperazinyl-3-pyridyl) furan, diethyl (3-pyrazin-2-yl (4-pyridyl)) amine, and dimethyl {2- [2- (5- methylpyrazin-2-yl) ethynyl] (4-pyridyl)} amine.

"Optionally substituted"refers to the optional replacement of hydrogen with one or more monovalent or divalent radicals. Optionally substituted groups include those described herein, for each group in which a distinct definition for substitution is supplied. Additionally, suitable substitution groups include, for example, hydroxyl, nitro, amino, imino, cyano, halo, thio, thioamido, amidino, imidino, oxo, oxamidino, methoxamidino, imidino, guanidino, sulfonamido, carboxyl, formyl, alkyl, substituted alkyl, haloloweralkyl, loweralkoxy, haloloweralkoxy, loweralkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heteroarylcarbonyl, heteroaralkylcarbonyl, alkylthio, aminoalkyl, cyanoalkyl, benzyl, pyridyl, pyrazolyl, pyrrole, thiophene, imidazolyl, and the like.

Representative substituted amidino and heterocycloamidino groups include, for example, those shown below. These amidino and heterocycloamidino groups can be further substituted as will be apparent to those having skill in the organic and medicinal chemistry arts in conjunction with the disclosure herein.

Representative substituted alkylcarbonylamino, alkyloxycarbonylamino, aminoalkyloxycarbonylamino, and arylcarbonylamino groups include, for example, those shown below. These groups can be further substituted as will be apparent to those having skill in the organic and medicinal chemistry arts in conjunction with the disclosure herein.

Representative substituted aminocarbonyl groups include, for example, those shown below.

These can be further substituted by heterocyclo groups and heteroaryl groups as will be apparent to those having skill in the organic and medicinal chemistry arts in conjunction with the disclosure herein. Prefered aminocarbonyl groups include: N- (2-cyanoethyl) carboxamide, N- (3- methoxypropyl) carboxamide, N-cyclopropylcarboxamide, N- (2-hydroxy-isopropyl) carboxamide, methyl 2-carbonylamino-3-hydroxypropanoate, N- (2-hydroxypropyl) carboxamide, N- (2-hydroxy- isopropyl) carboxamide, N-[2-hydroxy-1-(hydroxymethyl) ethyl] carboxamide, N- (2- carbonylaminoethyl) acetamide, N- (2- (2-pyridyl) ethyl) carboxamide, N- (2-pyridylmethyl) carboxamide, N- (oxolan-2-ylmethyl) carboxamide, N- (4-hydroxypyrrolidin-2-yl) carboxamide, N- [2- (2- hydroxyethoxy) ethyl] carboxamide, N- (4-hydroxycyclohexyl) carboxamide, N-[2-(2-oxo-4- imidazolinyl) ethyl] carboxamide, N- (carbonylaminomethyl) acetamide, N- (3- pyrrolidinylpropyl) carboxamide, N-[l-(carbonylaminomethyl) pyrrolidin-3-yl] acetamide, N- (2- morpholin-4-ylethyl) carboxamide, N- [3- (2-oxopyrrolidinyl) propyl] carboxamide, 4-methyl-2- oxopiperazinecarbaldehyde, N-(2-hydroxy-3-pyrrolidinylpropyl) carboxamide, N- (2-hydroxy-3- morpholin-4-ylpropyl) carboxamide, N-{2-[(5-cyano-2-pyridyl) amino] ethyl} carboxamide, 3- (dimethylamino) pyrrolidinecarbaldehyde, N- [ (5-methylpyrazin-2-yl) methyl] carboxamide, 2, 2,2- trifluoro-N- (l-formylpyrrolidin-3-yl) acetamide, Representative substituted alkoxycarbonyl groups include, for example, those shown below.

These alkoxycarbonyl groups can be further substituted as will be apparent to those having skill in the organic and medicinal chemistry arts in conjunction with the disclosure herein.

The term"protected"with respect to hydroxyl groups, amine groups, and sulfhydryl groups refers to forms of these functionalities that are protected from undesirable reaction with a protecting group known to those skilled in the art such as those set forth in Protective Groups in Organic Synthesis, Greene, T. W.; Wuts, P. G. M. , John Wiley & Sons, New York, NY, (3rd Edition, 1999) that can be added or removed using the procedures set forth therein. Examples of protected hydroxyl groups include, but are not limited to, silyl ethers such as those obtained by reaction of a hydroxyl group with a reagent such as, but not limited to, t-butyldimethyl-chlorosilane, trimethylchlorosilane, triisopropylchlorosilane, triethylchlorosilane ; substituted methyl and ethyl ethers such as, but not limited to methoxymethyl ether, methythiomethyl ether, benzyloxymethyl ether, t-butoxymethyl ether, 2-methoxyethoxymethyl ether, tetrahydropyranyl ethers, 1-ethoxyethyl ether, allyl ether, benzyl ether; esters such as, but not limited to, benzoylformate, formate, acetate, trichloroacetate, and trifluoracetate.

Examples of protected amine groups include, but are not limited to, amides such as, formamide, acetamide, trifluoroacetamide, and benzamide ; imides, such as phthalimide, and dithiosuccinimide ; and others. Examples of protected sulfhydryl groups include, but are not limited to, thioether such as S-benzyl thioether, and S-4-picolyl thioether ; substituted S-methyl derivatives such as hemithio, dithio and aminothio acetals; and others.

A"pharmaceutically acceptable salt"includes a salt with an inorganic base, organic base, inorganic acid, organic acid, or basic or acidic amino acid. As salts of inorganic bases, the invention includes, for example, alkali metals such as sodium or potassium ; alkaline earth metals such as calcium and magnesium or aluminum ; and ammonia. As salts of organic bases, the invention includes, for example, trimethylamine, triethylamine, pyridine, picoline, ethanolamine, diethanolamine, and triethanolamine. As salts of inorganic acids, the instant invention includes, for example, hydrochloric acid, hydroboric acid, nitric acid, sulfuric acid, and phosphoric acid. As salts of organic acids, the instant invention includes, for example, formic acid, acetic acid, trifluoroacetic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid. As salts of basic amino acids, the instant invention includes, for example, arginine, lysine and ornithine. Acidic amino acids include, for example, aspartic acid and glutamic acid.

As used herein, the term"pharmaceutically acceptable ester"refers to esters that hydrolyze in vivo and include those that break down readily in the human body to leave the parent compound or a salt thereof. Suitable ester groups include, for example, those derived from pharmaceutically acceptable aliphatic carboxylic acids, particularly alkanoic, alkenoic, cycloalkanoic and alkanedioic acids, in which each alkyl or alkenyl moiety advantageously has not more than 6 carbon atoms.

Representative examples of particular esters include, but are not limited to, formates, acetates, propionates, butyrates, acrylates and ethylsuccinates.

The term"pharmaceutically acceptable prodrugs"as used herein refers to those prodrugs of the compounds of the present invention that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use, as well as the zwitterionic forms, where possible, of the compounds of the invention.

The term"prodrug"refers to compounds that are rapidly transformed in vivo to yield the parent compound of the above formula, for example by hydrolysis in blood. A thorough discussion is provided in T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14 of the A. C. S.

Symposium Series, and in Edward B. Roche, ed. , Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987, both of which are incorporated herein by reference.

The term"antibacterial agent"refers to agents synthesized or modified in the laboratory that have either bactericidal or bacteriostatic activity. An"active"agent in this context will inhibit the growth of P. aeruginosa and other gram-negative bacteria. The term"inhibiting the growth"indicates that the rate of increase in the numbers of a population of a particular bacterium is reduced. Thus, the term includes situations in which the bacterial population increases but at a reduced rate, as well as situations where the growth of the population is stopped, as well as situations where the numbers of the bacteria in the population are reduced or the population even eliminated. If an enzyme activity assay is used to screen for inhibitors, one can make modifications in uptake/efflux, solubility, half-life, etc. to compounds in order to correlate enzyme inhibition with growth inhibition. The activity of antibacterial agents is not necessarily limited to bacteria but may also encompass activity against parasites, virus, and fungi.

The subject invention also includes isotopically-labeled LpxC inhibitors, that are structurally identical to those disclosed above, 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 isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine and chlorine, such as 2H, 3H, 13C, 14C, l5N, 18O, 17O, 31p, 32p, 35S, l8F and 36C1, respectively. Compounds of the present invention, prodrugs thereof, and pharmaceutically acceptable salts of said compounds and of said prodrugs that contain the aforementioned isotopes and/or other isotopes of other atoms are within the scope of this invention. Certain isotopically labeled compounds of the present invention, for example those into which radioactive isotopes such as 3H and 14C are incorporated, are useful in drug and/or substrate tissue distribution assays. Tritiated, i. e., 3H, and carbon-14, i. e., 14C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium, i. e., 2H, may 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 labeled compounds of this invention and prodrugs thereof can generally be prepared by carrying out known or referenced procedures and by substituting a readily available isotopically labeled reagent for a non-isotopically labeled reagent.

The present invention provides novel compounds, pharmaceutical formulations including the compounds, methods of inhibiting UDP-3-0-(R-3-hydroxydecanoyl)-N-acetylglucosamine deacetylase (LpxC), and methods of treating gram-negative bacterial infections.

In one embodiment, the present invention provides compounds of formula I : I or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein E is absent or selected from the group consisting of (1) H, (2) substituted or unsubstituted Cl-C6-alkyl, (3) substituted or unsubstituted C2-C6-alkenyl, (4) substituted or unsubstituted C2-C6-alkynyl, (5) substituted or unsubstituted aryl, (6) substituted or unsubstituted heterocyclyl, and (7) substituted or unsubstituted heteroaryl ; L is absent or selected from the group consisting of (1) substituted or unsubstituted Cl-C6-alkyl, (2) -(NH)0-1-(CH2)j-NR3L-(CH2)k-, (3) -(NH)0-1-C(R1L,R2L)-NR3L-C(R1L,R2L)-, (4) -C(R1L,R2L)-O-C(R1L,R2L)-, (5) (CH2)j-NR3L-C(R1L,R2L)-CONH-(CH2)k-, (6)-CO-C (RlL, R2L) NHCO-, (7) -CONH-, (8) -NHCO-, wherein RlL, R2L, and R3L are independently selected from the group consisting of (a) H, (b) substituted or unsubstituted Cl-C6-alkyl, (c) Cl-C6-alkyl substituted with aryl, (d) Cl-C6-alkyl substituted with heterocyclyl, and (e) Cl-C6-alkyl substituted with heteroaryl, or ruz and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S, j is an integer of 0-4; k is an integer of 0-4 ; D is absent or selected from the group consisting of (1) substituted or unsubstituted C3-C8-cycloalkyl, (2) substituted or unsubstituted aryl, (3) substituted or unsubstituted heterocyclyl, and (4) substituted or. unsubstituted heteroaryl; G is absent or selected from the group consisting of (1)- (CH2) i-O-(CH2)i-, (2) -(CH2)i-S-(CH2)i-, (3) -(CH2)i-NRg-(CH2)i-, (4) -C (=O)-, (5) -NHC (=O)-, (6) -C (=O) NH-, <BR> <BR> <BR> (7)- (CH2) iNHCH2C (=O) NH-,<BR> <BR> <BR> <BR> <BR> <BR> <BR> (8) -C#C-,<BR> <BR> <BR> <BR> <BR> (9) -C#C-C#C-, and<BR> <BR> <BR> <BR> <BR> <BR> (10)-C=C-; wherein Rg is H or substituted or unsubstituted CI-C6-alkyl ; i is an interger of 0-4; Y is selected from the group consisting of (1) substituted or unsubstituted C3-Cg-cycloalkyl, (2) substituted or unsubstituted aryl, (3) substituted or unsubstituted heterocyclyl, and (4) substituted or unsubstituted heteroaryl; X is selected from the group consisting of (1)- (C=O)-, (2) -C1-C6-alkyl-(C=O)-, (3)-C2-C6-alkenyl- (C=O)-, (4)-C2-C6-alkynyl- (C=O)-, and (5) -CH2-; or when B is absent, X and A, together with the atoms to which they are attached can form a heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic. ring system are selected from N, O and S; B is a absent or wherein Rlb and R2b, are independently selected from the group consisting of (a) H, (b) substituted or unsubstituted Cl-C6-alkyl, (c) substituted or unsubstituted C2-C6-alkenyl, (d) substituted or unsubstituted C2-C6-alkynyl, (e) substituted or unsubstituted aryl, (f) substituted or unsubstituted heterocyclyl, (g) substituted or unsubstituted heteroaryl, (h) Cl-C6-alkyl substituted with aryl, (i) Cl-C6-alkyl substituted with heterocyclyl, and (j) C1-C6-alkyl substituted with heteroaryl, or Rlb and together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S; q is an integer of 0-4; R3 is H or substituted or unsubstituted C1-C6-alkyl, or R3 and A, together with the atoms to which they are attached can form a substituted or unsubstituted 3-10 membered cycloalkyl or a heterocyclic ring system, wherein the heterocyclic ring system may have from 3 to 10 ring atoms, with 1 to 2 rings being in the ring system and contain from 1-4 heteroatoms selected from N, O and S; R4 is H or substituted or unsubstituted Cl-C6-alkyl, or R4 and A, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S; n is an integer of 0-2; A is selected from the group consisting of (1) H, (2) - dCH2) rC (R1a,R2a)(CH2)sOR3a, (3) (CH2) rC (RIaR2a) N (R4a Wa), (4)- (CH2) rC (R1a, R2a) N (R4a) COR3a, (5) -(CH2)rC(R1a,R2a)NHCON(R4a,R5a), (6)- (CH2),. C (Rla, R2a) NHC (=NH) N(R4a,R5a), (7) -CH(R1a,R2a), (8)-C=CH, (9) -(CH2)rC(R1a,R2a) CN, (10) -(CH2)rC(R1a,R2a)CO2R3a, and (11)- (CH2) rC (R1a,R2a)CN(R4a,R5a), wherein Rla, R2a, R3a, R4a, and Rare independently selected from the group consisting of (a) H, (b) substituted or unsubstituted C1-C6-alkyl, (c) substituted or unsubstituted aryl, (d) substituted or unsubstituted heterocyclyl, (e) substituted or unsubstituted heteroaryl, (f) Cl-C6-alkyl substituted with aryl, (g) Cl-C6-alkyl substituted with heterocyclyl, and (h) Cl-C6-alkyl substituted with heteroaryl, or R4a and R5a together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S; r is an integer of 0-4; s is an integer of 0-4; Q is absent or selected from the group consisting of (1) -C(=O) N (R1, R2), (2)-NHC (=O) N (RI, R2), (3) -N (OH) C (=O) N (Rl, R2), (4) -CH (OH) C (=O) N (Ri, R2), (5) -CH [N (R2q, R3q)]C(=O) N (R1, R2), (6) -CHR1qC (=O) N (Ri, R2), (7) -CO2H, (8) -C(=O)NHSO2R4q, (9)-S02NH2, (10)-N (OH) C (=O) R, (11) -N(OH)SO2R4q, (12) -NHSO2R4q, (13)-SH, (14) -CH (SH) (CH2) 0-1C (=O) N (RI, R2), (15) -CH (SH) (CH2) 0-1CO2H, (16)-CH (OH) (CH2) 0-1CO2H, (17) -CH (SH) CH2CO2Rlq, (18) -CH (OH) (CH2) SO2NH2, (19) -CH(CH2SH)NHCOR1q, (20)-CH (CH2SH) NHSO2R4q, (21) -CH(CH2SR5q)CO2H, (22) -CH (CH2SH) NHSO2NH2, (23) -CH (CH2OH) C02H, (24)-CH (CH20H) NHS02NH2, (25) -C (=O) CH2CO2H, (26) -C (=O) (CH2) 0-1CONH2, (27)-OSO2NHRsq, Rl is selected from the group consisting of (1)-H, (2) -OH, (3)-OCl 6-alkyl, (4)-N (R2q, R39), and (5) substituted or unsubstituted Cl 6-alkyl ; R2 is selected from the group consisting of (1) H, (2) substituted or unsubstituted Cl-C6-alkyl, (3) substituted or unsubstituted C2-C6-alkenyl, (4) substituted or unsubstituted C2-C6-alkenyl, (5) substituted or unsubstituted aryl, (6) substituted or unsubstituted heterocyclyl, (7) substituted or unsubstituted heteroaryl, (8) Cl-C6-alkyl substituted with aryl, (9) Cl-C6-alkyl substituted with heterocyclyl, and (10) Cl-C6-alkyl substituted with heteroaryl, or R1 and R2, together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, 0 and S, R1q, R2q, R3q, R4q, and R5q are selected from H or Cl-C6 alkyl, wherein B is absent, or E, L, G, and B are absent, or E, L, and G are absent, or E, L, and B are absent, or E, L, D, G, and B are absent.

In another embodiment, the present invention provides compounds of formula I: or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein E is absent or selected from the group consisting of (1) H, (2) substituted or unsubstituted Cl-C6-alkyl, (3) substituted or unsubstituted aryl, (4) substituted or unsubstituted heterocyclyl, and (5) substituted or unsubstituted heteroaryl ; L is absent or selected from the group consisting of (1) -(CH2) J NR3L (CH2) k-, <BR> <BR> (2) -C(R1L,R2L)j-NR3L-C(R1L,R2L)k-,<BR> (3) -C(R1L,R2L)j-O-C(R1L,R2L)k-, (4) -(CH2)j-NR3L-C(R1L,R2L)k-CONH-(CH2)k-, (5) -CO-C(R1L,R2L)-NHCO-, (6) -CONH-, and (7)-NHCO-, wherein RlL, R2L, R3L are independently selected from the group consisting of (a) H, (b) substituted or unsubstituted Cl-C6-alkyl, (c) Cl-C6-alkyl substituted with aryl, (d) Cl-C6-alkyl substituted with heterocyclyl, (e) Cl-C6-alkyl substituted with heteroaryl, or RIL and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S; j is an integer of 0-4; k is an integer of 0-4 ; D is absent or selected from the group consisting of (1) substituted or unsubstituted C3-C8-cycloalkyl, (2) substituted or unsubstituted aryl, (3) substituted or unsubstituted heterocyclyl, (4) substituted or unsubstituted heteroaryl, and G is absent or selected from the group consisting of (1) -C(=O)-, (2) -NHC(=O)-, (4)- (CH2)iNHCH2C(=O)NH-, (5) -C#C-, and (6) wherein i is an interger of 0-4 ; Y is selected from the group consisting of (1) substituted or unsubstituted C3-C8-cycloalkyl, (2) substituted or unsubstituted aryl, (3) substituted or unsubstituted heterocyclyl, and (4) substituted or unsubstituted heteroaryl; X is selected from the group consisting of (1) -(C=O)-, (2) -C1-C6-alkyl- (C=Oy, (3)-C2-C6-alkenyl- (C=O)-, (4) -C2-C6-alkynyl-(C=O)-, and (5) -CH2-; or when B is absent, X and A, together with the atoms to which they are attached can form a heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S; B is absent or wherein Rlb and R2b are independently selected from the group consisting of (a) H (b) substituted or unsubstituted Cl-C6-alkyl, (c) substituted or unsubstituted C2-C6-alkenyl, (d) substituted or unsubstituted C2-C6-alkenyl, (e) substituted or unsubstituted aryl, (f) substituted or unsubstituted heterocyclyl, (g) substituted or unsubstituted heteroaryl, (h) Cl-C6-alkyl substituted with aryl, (i) Cl-C6-alkyl substituted with heterocyclyl, and (j) Cl-C6-alkyl substituted with heteroaryl, or Rlb and R2b, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S; q is an integer of 0-2; R3 is H or substituted or unsubstituted Cl-C6-alkyl, or R3 and A, together with the atoms to which they are attached can form a substituted or unsubstituted 3-10 membered cycloalkyl or a heterocyclic ring system, wherein the heterocyclic ring system may have from 3 to 10 ring atoms, with 1 to 2 rings being in the ring system and contain from 1-4 heteroatoms selected from N, O and S; R4 is H or substituted or unsubstituted Cl-C6-alkyl, or R4 and A, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S; A is selected from the group consisting of (1) H, (2) -(CH2)rC(R1a,R2a)(CH2)sOR3a, (3) -(CH2)rC(R1a,R2a)N(R4a,5Ra), (4)- (CH2)@ C(R1a,R2a)N(R4a)COR3a, (5) - (CH2) C (Rla, R2a) NHCON (R4a, Ra), (6)- (CH2)@ rC (Rla, R2a)NHC(=NH) N (R4a RSa) <BR> <BR> <BR> (7) -CH(R1a,R2a),<BR> (8) -C#CH, (9)- (CH2) rC (Rla, R2a) CN, and (10)- (CH2) rC (R1a,R2a)CO2R3A, wherein Rla, Rota, R3a, R4a, and R5a, are independently selected from the group consisting of (a) H, (b) substituted or unsubstituted C1-C6-alkyl, (c) Cl-C6-alkyl substituted with aryl, (d) Cl-C6-alkyl substituted with heterocyclyl, and (e) Cl-C6-alkyl substituted with heteroaryl, or R4a and Rusa, together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 5 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S; r is an integer of 0-4; Q is absent or selected from the group consisting of (1)-C (=O) N (Ri, R2), (2) -NHC(=O)N(R1,R2), (3)-N (OH) C (=0) N (Rl, R2), (4) -CH (OH) C (=O) N (Rl, Rz), (5)-CH [N (R2q, R3q) C (=O) N (R1, Rz), and (6)-CHRIqC (=O) N (Rl, R2), RI is selected from the group consisting of (1) H, (2) OH, (3) OC1-6alkyl, (4) N (R2q, R3q), and (5) substituted or unsubstituted C1-6-alkyl ; R2 is selected from the group consisting of (1) H, (2) substituted or unsubstituted Cl-C6-alkyl, (3) substituted or unsubstituted aryl, (4) substituted or unsubstituted heterocyclyl, (5.) substituted or unsubstituted heteroaryl, (6) Cl-C6-alkyl substituted with aryl, (7) C1-C6-alkyl substituted with heterocyclyl, and (8) Cl-C6-alkyl substituted with heteroaryl, or Rland R2, together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S, Rlq, R2q, and R3q are selected from H or CI-C6 alkyl, wherein B is absent, or E, L, G, and B are absent, or E, L, and G are absent, or E, L, and B are absent, or E, L, D, G, and B are absent.

In another embodiment, the present invention provides compounds of formula II : or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein D-G-Y taken together, is selected from the group consisting of Wherein R is selected from the group consisting of-CH3,-C2Hs,-CH20H,-0H,-OCH3,-OC2Hs,- OCF3,-CN,-N02,-C02H,-C02CH3,-CONH2,-NH2,-F,-Cl,-Br,-CF3,-N (CH3) 2,- NHS02CH3, and-NHCOCH3 ; X is selected from the group consisting of (1)- (C=O)-, (2) -C1-C6-alkyl-(C=O)-, and (3) -C2-C6-alkenyl-(C=O)-.

In another embodiment, the present invention provides compounds of formula m : or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein D-G-Y taken together, is selected from the group consisting of Wherein R is selected from the group consisting of-CH3,-C2Hs,-CH20H,-OH,-OCH3,-OC2H5,- OCF3,-CN,-NO2,-CO2H,-CO2CH3,-CONH2,-NH2,-F,-Cl,-Br,-CF3,-N (CH3) 2,- NHS02CH3, and-NHCOCH3 ; X is selected from the groups consisting of (1)- {C=O)-, (2) -C1-C6-alkyl-(C=O)-, and (3) -C2-C6-alkenyl-(C=O)-.

In another embodiment, the present invention provides compounds of formula IV: or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein D-G-Y taken together, is selected from the group consisting of Wherein R is selected from the group consisting of-CH3, -C2H5, -CH2OH, -OH, -OCH3, -OC2H5, - OCF3, -CN, -NO2, -CO2H, -CO2CH3, -CONH2, -NH2, -F, -Cl, -Br, -CF3, -N(CH3)2, - NHSO2CH3, and-NHCOCH3 ; X is selected from the groups consisting of (1) -(C=O)-, (2)-Cl-C6-alkyl- (C=O)-, and (3)-C2-C6-alkenyl- (C=O)-.

In another embodiment, the present invention provides compounds of formula V: . V or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein D-G-Y taken together, is selected from the group consisting of Wherein R is selected from the group consisting of-CH3,-C2Hs,-CH20H,-OH,-OCH3,-OC2Hs,- OCF3,-CN,-NO2,-C02H,-C02CH3,-CONH2,-NHz,-F,-Cl,-Br,-CF3,-N (CH3) 2,- NHSO2CH3, and-NHCOCH3 ; X is selected from the groups consisting of (1) -(C=O)-, (2)-Cl-C6-alkyl-(C=O)-, and (3)-C2-C6-alkenyl- (C=O)-.

In another embodiment, the present invention provides compounds of formula VI: VI or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein E is absent or selected from the group consisting of (1) H, (2) substituted or unsubstituted C1-C6-alkyl, (3) substituted or unsubstituted aryl, (4) substituted or unsubstituted heterocyclyl, and (5) substituted or unsubstituted heteroaryl, or E and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S, R1L, R3L are independently selected from the group consisting of (1) H, (2) substituted or unsubstituted C1-C6-alkyl, (3) Cl-C6-alkyl substituted with aryl, (4) Cl-C6-alkyl substituted with heterocyclyl, and (5) Cl-C6-alkyl substituted with heteroaryl, or RI L and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.

In another embodiment, the present invention provides compounds of formula VII : Vil or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein E is absent or selected from the group consisting of (1) H,.

(2) substituted or unsubstituted Cl-C6-alkyl, (3) substituted or unsubstituted aryl, (4) substituted or unsubstituted heterocyclyl, and (5) substituted or unsubstituted heteroaryl, or E and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S; RlL, R3L are independently selected from the group consisting of (1) H, (2) substituted or unsubstituted C1-C6-alkyl, (3) Cl-C6-alkyl substituted with aryl, (4) C1-C6-alkyl substituted with heterocyclyl, and (5) C1-C6-alkyl substituted with heteroaryl, or R, I together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.

In another embodiment, the present invention provides compounds of formula VIII : or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein E is absent or selected from the group consisting of (1) H, (2) substituted or unsubstituted Cl-C6-alkyl, (3) substituted or unsubstituted aryl, (4) substituted or unsubstituted heterocyclyl, and (5) substituted or unsubstituted heteroaryl, . or E and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S; RlL, R3L are independently selected from the group consisting of (1) H, (2) substituted or unsubstituted Cl-C6-alkyl, (3) Cl-C6-alkyl substituted with aryl, (4) Cl-C6-alkyl substituted with heterocyclyl, and (5) Cl-C6-alkyl substituted with heteroaryl, or RIL and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.

In another embodiment, the present invention provides compounds of formula IX : or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein E is absent or selected from the group consisting of (1) H, (2) substituted or unsubstituted Cl-C6-alkyl, (3) substituted or unsubstituted aryl, (4) substituted or unsubstituted heterocyclyl, and (5) substituted or unsubstituted heteroaryl, or E and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S ; RIL, R3L are independently selected from the group consisting of (1) H, (2) substituted or unsubstituted Cl-C6-alkyl, (3) Cl-C6-alkyl substituted with aryl, (4) Cl-C6-alkyl substituted with heterocyclyl, and (5) Cl-C6-alkyl substituted with heteroaryl, or RIL and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.

In another embodiment, the present invention provides compounds of formula X: or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein E is absent or selected from the group consisting of (1) H, (2) substituted or unsubstituted C1-C6-alkyl, (3) substituted or unsubstituted aryl, (4) substituted or unsubstituted heterocyclyl, and (5) substituted or unsubstituted heteroaryl, or E and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-4 ring atoms of the heterocyclic ring system are selected from N, O and S; Roll, R3L are independently selected from the group consisting of (1) H, (2) substituted or unsubstituted Ci-C6-alkyl, (3) Cl-C6-alkyl substituted with aryl, ß (4) Cl-C6-alkylsubstitutedwithheterocyclyl, and (5) Cl-C6-alkyl substituted with heteroaryl, or R1L and R3L, together with the atoms to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 8 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.

In another embodiment, the present invention provides compounds of formula XI: or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein Y-X taken together, is selected from the group consisting of In another embodiment, the present invention provides compounds of formula XII : XII or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein Rlb and R2b are independently selected from the group consisting of (1) H, (2) substituted or unsubstituted Cl-C6-alkyl, (3) substituted or unsubstituted C2-C6-alkenyl, (4) substituted or unsubstituted C2-C6-alkenyl, (5) substituted or unsubstituted aryl, (6) substituted or unsubstituted heterocyclyl, (7) substituted or unsubstituted heteroaryl, (8) C1-C6alkyl substituted with aryl, (9) Cl-C6-alkyl substituted with heterocyclyl, and (10) Cl-C6-alkyl substituted with heteroaryl ; q is an integer of 0-2 ; In another embodiment, the present invention provides compounds of formula XIII- xm or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein R4 is selected from the group consisting of (1) H, (2) substituted or unsubstituted Cl-C6-alkyl, (3) Cl-C6-alkyl substituted with aryl, (4) Cl-C6-alkyl substituted with heterocyclyl, and (5) Cl-C6-alkyl substituted with heteroaryl; A is H or-CH (CH3) OH- ; R1 is H or substituted or unsubstituted Cl 6-alkyl ; R2 is selected from the group consisting of (1) H, (2) substituted or unsubstituted Cl-C6-alkyl, (3) substituted or unsubstituted aryl, (4) substituted or unsubstituted heterocyclyl, (5) substituted or unsubstituted heteroaryl, (6) Cl-C6-alkyl substituted with aryl, (7) C1-C6-alkyl substituted with heterocyclyl, (8) Cl-C6-alkyl substituted with heteroaryl, or Rl and R2 together withthe N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.

In another embodiment, the present invention provides compounds of formula XIV : or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein D-G-Y taken together is selected from the group consisting of R-'ND/ 9 R/\ I \/R N/\ I R,/\ \ % R R R R N R-C w R X R= R R R Nv R = t== g > >- R-- v or Wherein R is selected from the group consisting of-CH3, -C2H5, -CH2OH, -OH, -OCH3, -OC2H5, - OCF3,-CN,-NO2,-CO2H,-CO2CH3,-CONH2,-NH2,-F,-Cl,-Br,-CF3,-N (CH3) 2,- NHS02CH3, and-NHCOCH3 ; R4 is selected from the group consisting of (1) H, (2) substituted or unsubstituted C1-C6-alkyl, (3) CI-C6-alkyl substituted with aryl, (4) Cl-C6-alkyl substituted with heterocyclyl, and (5) CI-C6-alkyl substituted with heteroaryl.

In another embodiment, the present invention provides compounds of formula XV: or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein D-G-Y taken together, is selected from the group consisting of Wherein R is selected from the group consisting of-CH3,-C2Hs,-CH2OH,-0H,-OCH3,-OC2Hs,- OCF3, -CN, -NO2, -CO2H, -CO2CH3, -CONH2, -NH2, -F, -Cl, -Br, -CF3, -N (CH3) 2,- NHSO2CH3, and -NHCOCH3; In another embodiment, the present invention provides compounds of formula XVI : XVI or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein D-G-Y taken together, is selected from the group consisting of Wherein R is selected from the group consisting of-CH3,-c2Hs-CH2OH,-OH,-OCH3,-OC2Hs,- OCF3,-CN,-NO2,-CO2H,-CO2CH3,-CONH2,-NH2,-F,-Cl,-Br,-CF3,-N (CH3) 2,- NHSO2CH3, and-NHCOCH3 ; R4 is selected from the group consisting of (1) H, (2) substituted or unsubstituted C1-C6-alkyl, (3) C1-C6-alkyl substituted with aryl, -alkyl substituted with heterocyclyl, and (5) Cl-C6-alkyl substituted with heteroaryl ; In another embodiment, the present invention provides compounds of formula XVII : XVII or stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein D-G-Y taken together, is selected from the group consisting of Wherein R is selected from the group consisting of-CH3,-C2HS,-CH2OH,-OH,-OCH3,-OC2H5,- OCF3,-CN,-N02,-C02H,-C02CH3,-CONH2,-NH2,-F,-Cl,-Br,-CF3,-N (CH3) 2, NHSO2CH3, and-NHCOCH3 ; In one aspect, the invention provides a method of inhibiting a deacetylase enzyme in a gram- negative bacteria, thereby affecting bacterial growth, comprising administering to a patient in need of such inhibition a compound of formula I.

In another aspect, the invention provides a method of inhibiting LpxC, thereby modulating the virulence of a bacterial infection, comprising administering to a patient in need of such inhibition a compound of formula I.

In some embodiments of the method of inhibiting LpxC using a compound of formula I, the ICso value of the compound is less than or equal to 10 uM with respect to LpxC. In other such embodiments, the ICso value is less than or equal to 1, uM, is less than or equal to 0. 1 FM, is less than or equal to 0. 050 uM, is less than or equal to 0.030 jim, is less than or equal to 0. 025 uM, or is less than or equal to 0. 010 pM.

In one aspect of the invention, methods for treating a subject comprising administering to the subject an antibacterially effective amount of a compound of formula I, together with a pharmaceutically acceptable carrier is provided. In a preferred embodiment of the method of treatment, the subject is a mammal and some embodiments, a human.

In another aspect, the invention provides a method of administering an inhibitory amount of a compound of formula I to fermentative or non-fermentative gram-negative bacteria. In a preferred embodiment of the method of administering an inhibitory amount of a compound of formula I to fermentative or non-fermentative gram-negative bacteria, the gram-negative bacteria are selected from the group consisting of Pseudomonas aeruginosa, Stenotrophomonas maltophila, Burkholderia cepacia, Alcaligenes xylosoxidans, Acinetobacter, Enterobacteriaceae, Haemophilus, Neisseria species.

In another embodiment, the invention provides a method of administering an inhibitory amount of a compound of formula I to gram-negative bacteria, such as Enterobacteriaceae that is selected from the group consisting of organisms such as Serratia, Proteus, Klebsiella, Enterobacter, Citrobacter, Salmonella, Providencia, Morganella, Cedecea, and Edwardsiella species and Escherichia coli.

Another embodiment of the invention provides a pharmaceutical composition comprising an effective amount of a compound of Formula I with a pharmaceutically acceptable carrier thereof.

Pharmaceutical formulations according to the present invention are provided which include any of the compounds described above in combination with a pharmaceutically acceptable carrier.

Another embodiment of the invention provides a method of co-administering the compound of formula I with other therapeutic agents that are selected for their particular usefulness against the condition that is being treated.

For example, the compound of formula I is useful in combination with other anti-bacterial agents. The compound of formula I augments the sensitivity of gram-negative bacteria to existing classes of antibacterials. Combinations of the presently disclosed compounds with other anti-bacterial agents are within the scope of the invention. Such anti-bacterial agents include, but are not limited to, erythromycin, rifampicin, Nalidixic acid, carbenicillin, bacitracin, cycloserine, fosfomycin, and vancomycin.

A further aspect of the invention is the use of LpxC inhibitors for the treatment of an infection, particularly a bacterial infection. A bacterial infection treated with the compounds of the invention can be a primary infection or a co-infection caused by a species of bacteria and one or more additional infectious agents selected from the group consisting of bacteria, virus, parasite and fungus.

The term"treating", as used herein, refers to reversing, alleviating, inhibiting the progress of, or preventing the disorder or condition to which such term applies, or one or more symptoms of such disorder or condition. The term"treatment", as used herein, refers to the act of treating, as"treating"is defined immediately above.

The compounds of the invention can be used for treating conditions caused by the bacterial production of endotoxin and, in particular, by gram-negative bacteria and bacteria that use LpxC in the biosynthesis of lipopolysaccharide (LPS) or endotoxin.

The compounds of the invention also are useful in the conditions that are caused or exacerbated by the bacterial production of lipid A and LPS or endotoxin, such as sepsis, septic shock, systemic inflammation, localized inflammation, chronic obstructive pulmonary disease (COPD) and acute exacerbations of chronic bronchitis (AECB). For these conditions, treatment includes the administration of a compound of the invention, or a combination of compounds of the invention, optionally with a second agent wherein the second agent is a second antibacterial agent or a second non-antibacterial agent.

For sepsis, septic shock, systemic inflammation, localized inflammation, chronic obstructive pulmonary disease (COPD) and acute exacerbations of chronic bronchitis (AECB), preferred second non-antibacterial agents include antiendotoxins including endotoxin receptor-binding antibodies, endotoxin-binding antibodies, antiCD14-binding protein antibodies antilipopolysaccharide-binding protein antibodies and tyrosine kinase inhibitors.

In treatment of serious or chronic respiratory tract infections, the compounds of the present invention may also be used with second non-antibacterial agents administered via inhalation.

Preferred non-antibacterial agents used in this treatment include anti-inflammatory steroids, non- steroidal anti-inflammatory agents, bronchiodilators, mucolytics, anti-asthma therapeutics and lung fluid surfactants. In particular, the non-antibacterial agent may be selected from a group consisting of albuterol, salbuterol, budesonide, beclomethasone, dexamethasone, nedocromil, beclomethasone, fluticasone, flunisolide, triamcinolone, ibuprofin, rofecoxib, naproxen, celecoxib, nedocromil, ipratropium, metaproterenol, pirbuterol, salmeterol, bronchiodilators, mucolytics, calfactant, beractant, poractant alfa, surfaxin and pulmozyme (also called dornase alfa).

The compounds of the invention can be used, alone or in combination with a second antibacterial agent for the treatment of a serious or chronic respiratory tract infection including serious lung and nosocomial infections such as those caused by Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, Serratia marcescens, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Burkholderia cepacia, Acinetobacter calcoaceticus, Alcaligenes xylosoxidans, Flavobacterium meningosepticum, Providencia stuartii and Citrobacter freund, community lung infections such as those caused by Haemophilus Influenzae, Legionella species, Moraxella catarrhalis, Branhamella catarrhalis, Enterobacter species, Acinetobacter species, Klebsiella species, and Proteus species, and infections caused by other bacterial species such as Neisseria species, Shigella species, Salmonella species, Helicobacter pylori, Vibrionaceae and Bordetella species as well as the infections is caused by a Brucella species, Francisella tularensis and/or Yersinia Pestis.

When used for treating Gram-negative bacteria, the compounds of the present invention can be used to sensitize gram-negative bacteria to the effects of a second agent.

When the compounds of the present invention are used in combination with a second antibacterial agent, non-limiting examples of antibacterial agents may be selected from the following groups: (1) Macrolides or ketolides such as erythromycin, azithromycin, clarithromycin and telithromycin; (2) Beta-lactams including penicillin, cephalosporin, and carbapenems such as carbapenem, imipenem, and meropenem; (3) Monobactams such as penicillin G, penicillin V, methicillin, oxacillin, cloxacillin, dicloxacillin, nafcillin, ampicillin, amoxicillin, carbenicillin, ticarcillin, mezlocillin, piperacillin, azlocillin, temocillin, cepalothin, cephapirin, cephradine, cephaloridine, cefazolin, cefamandole, cefuroxime, cephalexin, cefprozil, cefaclor, loracarbef, cefoxitin, cefmetazole, cefotaxime, ceftizoxime, ceftriaxone, cefoperazone, ceftazidime, cefixime, cefpodoxime, ceftibuten, cefdinir, cefpirome, cefepime, and astreonam; (4) Quinolones such as nalidixic acid, oxolinic acid, norfloxacin, pefloxacin, enoxacin, ofloxacin, levofloxacin, ciprofloxacin, temafloxacin, lomefloxacin, fleroxacin, grepafloxacin, sparfloxacin, trovafloxacin, clinafloxacin, gatifloxacin, moxifloxacin, sitafloxacin, ganefloxacin, gemifloxacin and pazufloxacin; (5) Antibacterial sulfonamides and antibacterial sulphanilamides, including para-aminobenzoic acid, sulfadiazine, sulfisoxazole, sulfamethoxazole and sulfathalidine ; (6) Aminoglycosides such as streptomycin, neomycin, kanamycin, paromycin, gentamicin, tobramycin, amikacin, netilmicin, spectinomycin, sisomicin, dibekalin and isepamicin; (7) Tetracyclines such as tetracycline, chlortetracycline, demeclocycline, minocycline, oxytetracycline, methacycline, doxycycline; (8) Rifamycins such as rifampicin (also called rifampin), rifapentine, rifabutin, bezoxazinorifamycin and rifaximin ; (9) Lincosamides such as lincomycin and clindamycin; (10) Glycopeptides such as vancomycin and teicoplanin; (11) Streptogramins such as quinupristin and daflopristin; (12) Oxazolidinones such as linezolid; (13) Polymyxin, colistin and colymycin ; (14) Trimethoprim and bacitracin.

The second antibacterial agent may be administered in combination with the compounds of the present inventions wherein the second antibacterial agent is administered prior to, simultaneously, or after the compound or compounds of the present invention. When simultaneous administration of a compound of the invention with a second agent is desired and the route of administration is the same, then a compound of the invention may be formulated with a second agent into the same dosage form.

An example of a dosage form containing a compound of the invention and a second agent is a tablet or a capsule.

When used for treating a serious or chronic respiratory tract infections, the compounds of the invention may be used alone or in combination with a second antibacterial agent administered via inhalation. In the case of inhalation, a preferred second antibacterial agent is selected from a group consisting of tobramycin, gentamicin, aztreonam, ciprofloxacin, polymyxin, colistin, colymycin, azithromycin and clarithromycin.

Pharmaceutical Compositions Pharmaceutical compositions of the present invention comprise a therapeutically effective amount of a compound of the present invention formulated together with one or more pharmaceutically acceptable carriers. As used herein, the term"pharmaceutically acceptable carrier" means a non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. Some examples of materials that can serve as pharmaceutically acceptable carriers are sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch ; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate ; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil; safflower oil; sesame oil; olive oil; corn oil and soybean oil; glycols; such a propylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water ; isotonic saline; Ringer's solution; ethyl alcohol, and phosphate buffer solutions, as well as other non- toxic compatible lubricants such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, releasing agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the composition, according to the judgment of the formulator. The pharmaceutical compositions of this invention can be administered to humans and other animals orally, rectally, parenterally, intracisternally, intravaginally, intraperitoneally, topically (as by powders, ointments, or drops), bucally, or as an oral or nasal spray, or a liquid aerosol or dry powder formulation for inhalation.

Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents.

Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution, suspension or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3- butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, U. S. P. and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono-or diglycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables.

The injectable formulations can be sterilized, for example, by filtration through a bacterial- retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions that can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use.

In order to prolong the effect of a drug, it is often desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution that, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form may be accomplished by dissolving or suspending the drug in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide- polyglycolide. Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly (orthoesters) and poly (anhydrides). Depot injectable formulations may also be prepared by entrapping the drug in liposomes or microemulsions that are compatible with body tissues.

Compositions for rectal or vaginal administration are preferably suppositories that can be prepared by mixing the compounds of this invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active compound.

Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid ; b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarding agents such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as, for example, acetyl alcohol and glycerol monostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also comprise buffering agents.

Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like.

The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient (s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes.

Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like.

The active compounds can also be in micro-encapsulated form with one or more excipients as noted above. The solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings and other coatings well known in the pharmaceutical formulating art. In such solid dosage forms the active compound may be admixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, e. g., tableting lubricants and other tableting aids such a magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient (s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes.

Dosage forms for topical or transdermal administration of a compound of this invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. The active component is admixed under sterile conditions with a pharmaceutically acceptable carrier and any needed preservatives or buffers as may be required. Ophthalmic formulations, ear drops, and the like are also contemplated as being within the scope of this invention.

The ointments, pastes, creams and gels may contain, in addition to an active compound of this invention, excipients such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof.

Compositions of the invention may also be formulated for delivery as a liquid aerosol or inhalable dry powder. Liquid aerosol formulations may be nebulized predominantly into particle sizes that can be delivered to the terminal and respiratory bronchioles where bacteria reside in patients with bronchial infections, such as chronic bronchitis and pneumonia. Pathogenic bacteria are commonly present throughout airways down to bronchi, bronchioli and lung parenchema, particularly in terminal and respiratory bronchioles. During exacerbation of infection, bacteria can also be present in alveoli.

Liquid aerosol and inhalable dry powder formulations are preferably delivered throughout the endobronchial tree to the terminal bronchioles and eventually to the parenchymal tissue.

Aerosolized formulations of the invention may be delivered using an aerosol forming device, such as a jet, vibrating porous plate or ultrasonic nebulizer, preferably selected to allow the formation of a aerosol particles having with a mass medium average diameter predominantly between 1 to 5 pm.

Further, the formulation preferably has balanced osmolarity ionic strength and chloride concentration, and the smallest aerosolizable volume able to deliver effective dose of the compounds of the invention to the site of the infection. Additionally, the aerosolized formulation preferably does not impair negatively the functionality of the airways and does not cause undesirable side effects.

Aerosolization devices suitable for administration of aerosol formulations of the invention include, for example, jet, vibrating porous plate, ultrasonic nebulizers and energized dry powder inhalers, that are able to nebulize the formulation of the invention into aerosol particle size predominantly in the size range from 1-5 um. Predominantly in this application means that at least 70% but preferably more than 90% of all generated aerosol particles are 1 to 5 pm range. A jet nebulizer works by air pressure to break a liquid solution into aerosol droplets. Vibrating porous plate nebulizers work by using a sonic vacuum produced by a rapidly vibrating porous plate to extrude a solvent droplet through a porous plate. An ultrasonic nebulizer works by a piezoelectric crystal that shears a liquid into small aerosol droplets. A variety of suitable devices are available, including, for example, AeroNeb and AeroDose vibrating porous plate nebulizers (AeroGen, Inc., Sunnyvale, California), Sidestream7 nebulizers (Medic-Aid Ltd. , West Sussex, England), Pari LC7 and Pari LC Star7 jet nebulizers (Pari Respiratory Equipment, Inc., Richmond, Virginia), and Aerosonic (DeVilbiss Medizinische Produkte (Deutschland) GmbH, Heiden, Germany) and UltraAire7 (Omron Healthcare, Inc., Vernon Hills, Illinois) ultrasonic nebulizers.

Compounds of the invention may also be formulated for use as topical powders and sprays that can contain, in addition to the compounds of this invention, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances.

Sprays can additionally contain customary propellants such as chlorofluorohydrocarbons.

Transdermal patches have the added advantage of providing controlled delivery of a compound to the body. Such dosage forms can be made by dissolving or dispensing the compound in the proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin.

The rate can be controlled by either providing a rate controlling membrane or by dispersing the compound in a polymer matrix or gel.

According to the methods of treatment of the present invention, bacterial infections are treated or prevented in a patient such as a human or lower mammal by administering to the patient a therapeutically effective amount of a compound of the invention, in such amounts and for such time as is necessary to achieve the desired result. By a"therapeutically effective amount"of a compound of the invention is meant a sufficient amount of the compound to treat bacterial infections, at a reasonable benefit/risk ratio applicable to any medical treatment. It will be understood, however, that the total daily usage of the compounds and compositions of the present invention will be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed ; and like factors well known in the medical arts.

The total daily dose of the compounds of this invention administered to a human or other mammal in single or in divided doses can be in amounts, for example, from 0. 01 to 50 mg/kg body weight or more usually from 0.1 to 25 mg/kg body weight. Single dose compositions may contain such amounts or submultiples thereof to make up the daily dose. In general, treatment regimens according to the present invention comprise administration to a patient in need of such treatment from about 10 mg to about 2000 mg of the compound (s) of this invention per day in single or multiple doses.

Methods of formulation are well known in the art and are disclosed, for example, in Remington : The Science and Practice of Pharmacy, Mack Publishing Company, Easton, Pa., 19th Edition (1995). Pharmaceutical compositions for use in the present invention can be in the form of sterile, non-pyrogenic liquid solutions or suspensions, coated capsules, suppositories, lyophilized powders, transdermal patches or other forms known in the art.

A"kit"as used in the instant application includes a container for containing the pharmaceutical compositions and may also include divided containers such as a divided bottle or a divided foil packet.

The container can be in any conventional shape or form as known in the art that is made of a pharmaceutically acceptable material, for example a paper or cardboard box, a glass or plastic bottle or jar, a resealable bag (for example, to hold a"refill"of tablets for placement into a different container), or a blister pack with individual doses for pressing out of the pack according to a therapeutic schedule.

The container employed can depend on the exact dosage form involved, for example a conventional cardboard box would not generally be used to hold a liquid suspension. It is feasible that more than one container can be used together in a single package to market a single dosage form. For example, tablets may be contained in a bottle that is in turn contained within a box.

An example of such a kit is a so-called blister pack. Blister packs are well known in the packaging industry and are being widely used for the packaging of pharmaceutical unit dosage forms (tablets, capsules, and the like). Blister packs generally consist of a sheet of relatively stiff material covered with a foil of a preferably transparent plastic material. During the packaging process, recesses are formed in the plastic foil. The recesses have the size and shape of individual tablets or capsules to be packed or may have the size and shape to accommodate multiple tablets and/or capsules to be packed. Next, the tablets or capsules are placed in the recesses accordingly and the sheet of relatively stiff material is sealed against the plastic foil at the face of the foil that is opposite from the direction in which the recesses were formed. As a result, the tablets or capsules are individually sealed or collectively sealed, as desired, in the recesses between the plastic foil and the sheet. Preferably the strength of the sheet is such that the tablets or capsules can be removed from the blister pack by manually applying pressure on the recesses whereby an opening is formed in the sheet at the place of the recess. The tablet or capsule can then be removed via said opening.

It maybe desirable to provide a written memory aid, where the written memory aid is of the type containing information and/or instructions for the physician, pharmacist or other health care provider, or subject, e. g. , in the form of numbers next to the tablets or capsules whereby the numbers correspond with the days of the regimen that the tablets or capsules so specified should be ingested or a card that contains the same type of information. Another example of such a memory aid is a calendar printed on the card e. g. , as follows"First Week, Monday, Tuesday,"... etc..."Second Week, Monday, Tuesday,..."etc. Other variations of memory aids will be readily apparent. A"daily dose"can be a single tablet or capsule or several tablets or capsules to be taken on a given day. When the kit contains separate compositions, a daily dose of one or more compositions of the kit can consist of one tablet or capsule while a daily dose of another one or more compositions of the kit can consist of several tablets or capsules.

Another specific embodiment of a kit is a dispenser designed to dispense the daily doses one at a time in the order of their intended use. Preferably, the dispenser is equipped with a memory-aid, so as to further facilitate compliance with the regimen. An example of such a memory-aid is a mechanical counter, that indicates the number of daily doses that has been dispensed. Another example of such a memory-aid is a battery-powered micro-chip memory coupled with a liquid crystal readout, or audible reminder signal that, for example, reads out the date that the last daily dose has been taken and/or reminds one when the next dose is to be taken.

The kits of the present invention may also include, in addition to LpxC inhibitors, one or more additional pharmaceutically active compounds. Preferably, the additional compound is another LpxC inhibitor or another compound useful to bacterial infections. The additional compounds may be administered in the same dosage form as the LpxC inhibitor or in different dosage forms. Likewise, the additional compounds can be administered at the same time as the LpxC inhibitor or at different times.

Compositions of the present compounds may also be used in combination with other known antibacterial agents of similar spectrum to (1) synergistically enhance treatment of severe Gram- negative infections covered by the spectrum of this compound or (2) add coverage in severe infections in which multiple organisms are suspected in which another agent of a different spectrum may be required in addition to this compound. Potential agents include members of the aminoglycosides, penicillins, cephalosporins, fluoroquinolones, macrolides, glycopeptides, lipopeptides and oxazolidinones. The treatment can involve administering a composition having both active agents or administration of the inventive compounds followed by or preceded by administration of an additional active antibacterial agent.

Characterization and Purification Methods Referring to the examples that follow, compounds of the present invention were characterized by high performance liquid chromatography (HPLC) using a Waters Millenium chromatography system with a 2690 Separation Module (Milford, Massachusetts). The analytical columns were Alltima C-18 reversed phase, 4.6 x 250 mm from Alltech (Deerfield, Illinois). A gradient elution was used, typically starting with 5% acetonitrile/95% water and progressing to 100% acetonitrile over a period of 40 minutes. All solvents contained 0. 1% trifluoroacetic acid (TFA). Compounds were detected by ultraviolet light (UV) absorption at either 220 or 254 nm. HPLC solvents were from Burdick and Jackson (Muskegan, Michigan), or Fisher Scientific (Pittsburg, Pennsylvania). In some instances, purity was assessed by thin layer chromatography (TLC) using glass or plastic backed silica gel plates, such as, for example, Baker-Flex Silica Gel 1 B2-F flexible sheets. TLC results were readily detected visually under ultraviolet light, or by employing well known iodine vapor and other various staining techniques.

Mass spectrometric analysis was performed on one of two LCMS instruments: a Waters System (Alliance HT HPLC and a Micromass ZQ mass spectrometer; Column: Eclipse XDB-C18, 2.1 x 50 mm ; solvent system: 5-95% (or 35-95%, or 65-95% or 95-95%) acetonitrile in water with 0.05% TFA; flow rate 0.8 mL/min; molecular weight range 500-1500; cone Voltage 20 V; column temperature 40°C) or a Hewlett Packard System (Series 1100 HPLC ; Column: Eclipse XDB-C18, 2.1 x 50 mm; solvent system: 1-95% acetonitrile in water with 0.05% TFA ; flow rate 0.4 mL/min ; molecular weight range 150-850; cone Voltage 50 V; column temperature 30°C). All masses are reported as those of the protonated parent ions.

GCMS analysis was performed on a Hewlet Packard instrument (HP6890 Series gas chromatograph with a Mass Selective Detector 5973; injector volume : 1 liL ; initial column temperature: 50°C ; final column temperature: 250C ; ramp time: 20 minutes ; gas flow rate : 1 mL/min ; column: 5% phenyl methyl siloxane, Model &num HP 190915-443, dimensions: 30.0 m x 25 m x 0.25 m).

Nuclear magnetic resonance (NMR) analysis was performed with a Varian 300 Mhz NMR (Palo Alto, California). The spectral reference was either TMS or the known chemical shift of the solvent. Some compound samples were run at elevated temperatures (e. g. 75°C) to promote increased sample solubility.

The purity of some of the invention compounds was assessed by elemental analysis (Desert Analytics, Tuscon, Arizona) Tuscon, Arizona) Melting points were determined on a Laboratory Devices Mel-Temp apparatus (Holliston, Massachusetts).

Preparative separations were carried out using a Flash 40 chromatography system and KP-Sil, 60A (Biotage, Charlottesville, Virginia), or by flash column chromatography using silica gel (230-400 mesh) packing material, or by HPLC using a C-18 reversed phase column. Typical solvents employed for the Flash 40 Biotage system and flash column chromatography were dichloromethane, methanol, ethyl acetate, hexane, acetone, aqueous hydroxyamine and triethyl amine. Typical solvents employed for the reverse phase HPLC were varying concentrations of acetonitrile and water with 0. 1% trifluoroacetic acid.

Compounds of the present invention can be readily synthesized using the methods described herein, or other methods, that are well known in the art. For example, the synthesis of hxdroxamic acids or similar scaffolds having a wide variety of substituents are comprehensively reviewed in Kline T, Andersen NH, Harwood EA, Bowman J, Malanda A, Endsley S, Erwin AL, Doyle M, Fong S, Harris AL, Mendelsohn B, Mdluli K, Raetz CR, Stover CK, Witte PR, Yabannavar A, Zhu S.,"Potent, novel in vitro inhibitors of the Pseudomonas aeruginosa deacetylase LpxC,"JMed Chem 2002 Jul 4; 45 (14): 3112-29; Patchett, A. A. , Nargund, R., Chen, M. -H., Nishi, H. R. , U. S. Patent 5,925, 659, 1999; Pirrung, M. C. , Chau, J. H. ,"A Convenient Procedure for the Preparation of Amino Acid Hydroxamates from Esters,"J Org. Chem. 1995, 60,8084-8085 ; Nhu, K. , Patel, D. V. ,"A New and Efficient Solid Phase Synthesis of Hydroxamic Acids,"J. Org Chem. 1997,62, 7088-7089; Patel, D., Nhu, K. ,"Methods for Solid-phase Synthesis of Hydroxylamine Compounds and Derivatives, and Combinatorial Libraries Thereof,"PCT WO 98/18754, 1998, Mellor, S. L., McGuire, C. , Chan, W. C., "N-Fmoc-aminoxy-2-chlortrityl Polystyrene Resin: A Facile Solid-phase Metliodology for the Synthesis of Hydroxamic Acids,"Tetrahedron Lett., 1997,38, 3311-3314; Khan, S. I., Grinstaff, M.

W.,"A Facile and Convenient Solid-phase Procedure for Synthesizing Nucleoside Hydroxamic Acids,"Terahedron. Lett., 1998,39, 8031-8034 ; Zhang, Y. , Li, D., Houtman, J. C. , Witiak, D. T., Seltzer, J.,. Bertics, P. J. , Lauhon, C. T.,"Design, Combinatorial Chemical Synthesis, and in vitro Characterization of Novel Urea Based Gelatinase Inhibitors,"Bioorg. Med. Chem. Lett., 1999,9, 2823-2826 ; Ito, Y. , Inubushi, Y. , Zenbayashi, M., Tomita, S. , Saegusa, T.,"Synthetic Reactions by Complex Catalysts. XXXI, A Novel and Versatile Method of Heterocycle Synthesis,"J Am Chem.

Soc., 1973, 95,4447-4448 ; Ito, Y. , Ito, I., Hirao, T. , Saegus, T. ,"Synthetic Reactions by Complex Catalysts XXXV,"Syn. Comnaun. 1974,4, 97-103; Witte, H. , Seliger, W.,"Cyclische Imidsaurester aus Nitrilen und Aminoalkoholen,"Liebigs Ann. Chem, 1974,996-1009 ; Pattenden, G. , Thom. S. M., "Naturally Occurring Linear Fused Thiazoline-Thiazole Containing Metabolites : Total Synthesis of (-) Didehydromirabazole A, a Cytotoxic Alkaloid from Blue-Green Algae,"J. Chem. Soc. Perkin Trans 1, 1993,1629-1636 ; Boyce, R. J., Mulqueen, G. C., Pattenden, G. , "Total Synthesis of Thiangazole, A Novel Naturally Occurring HIV-1 Inhibitor from Polyangium sp.."Tetrahedron, 1995, 51,7321-7330 ; Galeotti, N. , Plagnes, E. , Jouin, P.,"Synthesis of Peptidyl Aldehydes from Thiazolines,"lsetraAledron.

Lett. 1997,38, 2459-2462; Charette, A. B. , Chua, P. ,"Mild Method for the Synthesis of Thiazolines from Secondary and Tertiary Amides,"J. Org. Chem., 1998,63, 908-909; Bergeron, R. J. , Wiegand, J. , McManis, J. S. , McCosar, B. H. , Weimar, W. R., Brittenham, G. M., Smith, R. E.,"Effects of C-4 Stereochemistry and C-4'Hydroxylation on the Iron Clearing Efficiency and Toxicity of Desferrithiocin Analogues,"J. Med. Chem. 1999,42, 2432-2440 ; Raman, P., Razavik H., Kelly, J. W., "Titanium (IV)-mediated Tandem Deprotection-cyclodehydration of Protected Cysteine N-Amides: Biomimetic Synthesis of Thiazoline-and Thiazole-containing Heterocycles,"Org Lett., 2000,2, 3289-3292; Fernandez, X. , Fellous, R. , Dunach, E.,"Novel Synthesis of 2-Thioazolines,"Tetrahedro Lett., 2000,41, 3381-3384. Wipf, P. , Miller, C. P., Venkatraman, S. , Fritch, P.,"C. Thiolysis of Oxazolinenes : A New, Selective Method for the Direct Conversion of Peptide Oxazolines into Thiazolines,"Tetrahedron Lett., 1995,36, 6395-6398, which are incorporated herein by reference.

The synthesis of other non-hydroxamates compounds or more generally zinc binding groups are reviewed in Pirrung, M. C. , Tumey, L. N. , Raetz, C. R. H., Jackman, J. E., Snehalatha, K., McClerren, A. L., Fierke, C. A. , Gantt, S. L. , Rusche, K. M. ,"Inhibition of the Antibacterial Target UDP- (3-0-acyl)-N-acetylglucosamine Deacetylase (LpxC): Isoxazoline Zinc Amidase Inhibitors Bearing Diverse Metal Binding Groups, "Journal of Medicinal Chemistry (2002), 45 (19), 4359- 4370 ; Jackman, J. E., Fierke, C. A. , Tumey, L. N. , Pirrung, M. , Uchiyama, T. , Tahir, S. H. , Hindsgaul, O., Raetz, C. R. H. , "Antibacterial agents that target lipid A biosynthesis in gram-negative bacteria: inhibition of diverse UDP-3-O- (R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylases by substrate analogs containing zinc binding motifs,"Journal of Biological Chemistry (2000), 275 (15), 11002- 11009; Brooks, C. D. W. , Summers, J. B.,"Modulators of Leukotriene Biosynthesis and Receptor Activation,"Journal of Medicinal Chemistry (1996), 39 (14), 2629-2654; Jeng, A. Y. ; De Lombaert, S.,"Endothelin converting enzyme inhibitors, "Current Pharmaceutical Design (1997), 3 (6), 597-614 ; Zask, A. , Levin, J. I., Killar, L. M., Skotnicki, J. S. ,"Inhibition of matrix metalloproteinases : structure based design,"Current Pharmaceutical Design (1996), 2 (6), 624-661; Skotnicki, J. S., DiGrandi, M. J. , Levin, J. I., Chemical and Screening Sciences, Wyeth Research, New York, NY, USA. Current Opinion in Drug Discovery & Development (2003), 6 (5), 742-759.

The foregoing may be better understood by reference to the following examples, that are presented for illustration and not to limit the scope of the inventive concepts.

EXAMPLES The following are abbreviations used in the examples: AcOH : Acetic acid aq: Aqueous ATP: Adenosine triphosphate Boc: tert-butoxycarbonyl Boc-Thr (OBn)-OH 3- (R)-Benzyloxy-2- (S)-tert-butoxycarbonylamino-butyric acid.

DAP or Dap: Diaminopropionate DCM: 4- (Dicyanomethylene)-2-methyl-6- (4-dimethylaminostyryl)- 4H-pyran DEAD: Diethyl azodicarboxylate DIEA : Diisopropylethylamine DME : 1,2-dimethoxyethane DMF : N, N-Dimethylformamide DMSO: Dimethyl sulfoxide DPPA : Diphenyl phosphoryl azide Et3N: Triethylamine EDC: N- (3-Dimethylaminopropyl)-N'-ethylcarbodiimide EDCI: 1- (3-dimethylaminopropyl) 3-ethylcarbodiimide EtOAc: Ethyl acetate EtOH : Ethanol Fmoc: 9-fluorenylmethoxycarbonyl Gly-OH : glycine HATU: 0- (7-azabenzotriaazol-1-yl)-N, N, N'N'=tetramethyluronium hexafluorophophate HBTU: 2-(lH-benzotriazol-l-yl)-1, 1, 3, 3-tetramethyluronium hexafluorophosphate Hex: hexane HOBt : butyl alcohol HOBT : 1-Hydroxybenzotriazole HPLC: High Pressure Liquid Chromatography ICso value: The concentration of an inhibitor that causes a 50 % reduction in a measured activity. iPrOH : Isopropanol LC/MS: Liquid Chromatography/Mass Spectrometry LRMS: Low Resolution Mass Spectrometry MeOH : Methanol NaOMe: sodium methoxide nm : Nanometer NMP N-Methylpyrrolidone PPh3: triphenyl phosphine RP-HPLC : Reversed-phase high-pressure liquid chromatography RT : Room temperature sat: Saturated TEA: Triethylamine TFA: Trifluoroacetic acid THF : Tetrahydrofuran Thr: Threonine TLC: Thin Layer Chromatography Trt-Br: Tert-butyl bromide Nomenclature for the Example compounds was provided using ACD Name version 5.07 software (November 14,2001) available from Advanced Chemistry Development, Inc. Some of the compounds and starting materials were named using standard IUPAC nomenclature.

Synthesis of N-Aroyl Threonine Analogues and Formation of Hydroxamate Example 1: Synthesis of 3-bromo-4-fluoro-N-{(lS, 2R)-2-hydroxy-1-[(hydroxyamino) carbonyl] propyl} benzamide (3).

Reagent MW Eq. g/ml mmol Benzoic acid (1) 219.02 1.0 2.152 g 9.83 L-Thr-OMe-HCl 169.61 1.2 1. 968 g 11.6 EDCI 191. 71 1.2 2.218 g 11. 6 HOBt 135.13 1. 1 1.410 g 10. 4 DIEA 129.25 4. 0 6.8 mL 39.0 DMF 60 mL Preparation of (2S, 3R)-2- (3-bromo4-fluoro-benzoylamino)-3-hydroxy-butyric acid methyl ester (2) Diisopropylethylamine (6.8 mL, 39.0 mmol) was added to a stirred solution of 3-bromo-4- fluorobenzoic acid 1 (2.152 gi 9.83 mmol), L-threonine methyl ester hydrochloride (1.968 g, 11.6 mmol), EDCI (2.218 g, 11.6 mmol) and HOBt (1.410 g, 10.4 mmol) in anhydrous DMF (60 mL) at 0 °C under N2. The solution was stirred at 0 °C for 1 h and at room temperature for 20 h. The solution was diluted with EtOAc (300 mL) and washed with 1.0 M HCl (2 x 80 mL), saturated NaHCO3 (2 x 80 mL), H20 (4 x 80 mL), dried over MgS04, filtered and concentrated in vacuo to give a colorless syrup which solidified on standing to afford 3.280 g (100%) of (2S, 3R)-2- (3-bromo-4-fluoro- benzoylamino)-3-hydroxy-butyric acid methyl ester 2 as a white solid, mp 73-74 °C. MS (ES+) m/z 333.9 (Cl2Hl3BrFN04+H requires 334.00).

Preparation of 3-bromo-4-fluoro-N-{(1S, 2R)-2-hydroxy-1-[(hydroxyamino) carbonyl] propyl}benzamide (3) To a solution of hydroxylamine hydrochloride (66 mg, 0.95 mmol) in anhydrous MeOH (2.0 mL) at 0 °C under N2 atmosphere was added sodium methoxide (25 wt% in MeOH, 360 mg, 1.67 mmol). A precipitate formed immediately and the cloudy white solution was stirred for 10 minutes at 0 °C. A solution of methyl (2S, 3R)-2- [ (3-bromo-4-fluorophenyl) carbonylamino]-3-hydroxybutanoate (2) (284 mg, 0.850 mmol) in MeOH (2.0 mL) was added and the reaction stirred 2 h at 0 °C and then warmed gradually to room temperature overnight (17 h total). Aqueous 1.0 M HCI (10 mL) was added and the solution extracted with 4: 1 chloroform/isopropyl alcohol (4 x 20 mL). The organic layers were combined, dried over Na2S04 and concentrated to give a pink foam. The crude solid was triturated with diethyl ether (2 x 8 mL) and dried in vacuo to give 3-bromo4-fluoro-N-{(lS, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 3 as a white foam: mp 152-153 °C. Rf (10: 1 CH2Cl2/MeOH on silica gel) = 0.53.

Preparation of Hydroxamates Example 2: Synthesis of 4-benzoyl-N-{(lS, 2R)-2-hydroxy-1-[(hydroxyamino) carbonyl] benzamide Procedure: To a solution of hydroxylamine hydrochloride (121 mg, 1.74 mmol) in anhydrous MeOH (2.0 mL) at 0 °C under N2 atmosphere was added sodium methoxide (25 wt% in MeOH, 680 mg, 3.14 mmol). A precipitate was immediately observed and the cloudy white solution was stirred for 10 minutes at 0 °C. A solution of methyl (2S, 3R)-3-hydroxy-2-{[4- (phenylcarbonyl) phenyl] carbonylamino} butanoate (1) (534 mg, 1.56 mmol) in MeOH (3.0 mL) was added and the reaction stirred 3 h at 0 °C, then warmed gradually to ambient temperature overnight (18 h total). Aqueous 0.5 M HCl (20 mL) was added and the solution extracted with 5: 1 chloroform/isopropyl alcohol (4 x 40 mL). The organic layers were combined, dried over Na2SO4 and concentrated to give an orange foam. Purification by silica gel chromatography (increasing eluant polarity from 30: 1 CH2Cl2/MeOH to 15: 1 CH2ClMeOH) afforded 228 mg (43%) of 4-benzoyl-N- {(1S,2R)-2-hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide.

Example 3: Synthesis of (2R,3R)-3-hydroxy-1-{[4-(trifluoromethoxy)phenyl]carbonyl} pyrrolidine-2-carbohydroxamic acid Preparation of ((2R, 3R)-3-hydroxy-1-{[4-(trifluoromethoxy) phenyl] carbonyl} pyrrolidin-2-yl)- N- (phenylmethoxy) carboxamide (2) O OH H O /O O NH N benzylhydroxylamine HCI ..-OH F3Cs HATU, HOBt, DIEA, DMF N... OH O °C to r. t. F3Csow 1 2 Procedure: To a solution of (2R, 3R)-3-hydroxy-l- { [4- (trifluoromethoxy) phenyl] carbonyl} pyrrolidine-2- carboxylic acid (1) (405 mg, 1.27 mmol), benzylhydroxylamine hydrochloride (243 mg, 1.52 mmol), HATU (556 mg, 1.46 mmol), and HOBt (178 mg, 1.32 mmol) in DMF (10 mL) at 0 °C was added diisopropylethylamine (710 N, L, 4 : 07 mmol) with stirring. The cooling bath was removed after one hour and the reaction mixture stirred at ambient temperature for 18 h and then diluted with EtOAc (200 mL). The organic layer was washed with 1.0 M HCl (2 x 60 mL), sat. NaHC03 (2 x 60 mL) and H20 (5 x 60 mL), dried over MgS04 and concentrated to give 493 mg (92%) of ((2R, 3R)-3-hydroxy-1- {[4-(trifluoromethoxy) phenyl] carbonyl} pyrrolidin-2-yl)-N-(phenylmethoxy) carboxamide (2), a colorless oil that slowly crystallized upon standing. Rf (25 : 1 CH2Cl2/MeOH) = 0.35.

Prepartion of (2R, 3R)-3-hydroxy-1-{[4-(trifluoromethoxy)phenyl] carbonyl}pyrrolidine-2- carbohydroxamic acid (2) 1 2 Procedure: To a solution of ( (2R, 3R)-3-hydroxy-1-1 [4- (trifluoromethoxy) phenyl] carbonyllpyrrolidin-2- yl)-N- (phenylmethoxy) carboxamide (1) (143 mg, 0. 337 mmol) in EtOH (10 mL) was added 20% Pd (OH) 2/C (50 mg). The solution was purged with hydrogen gas (approx. 0.5 L from a 1 L balloon) and then stirred under an atmosphere of H2 (balloon pressure). TLC analysis showed no starting material after one hour. The solution was diluted with EtOAc (10 mL) and filtered through celite, washing with 20: 1 EtOAc/EtOH (50 mL). The solution was concentrated and dried in vacuo to afford 90 mg (80%) of (2R, 3R)-3-hydroxy-1-{[4-(trifluoromethoxy) phenyllcarbonyl} pyrrolidine-2- carbohydroxamic acid (2) as a sticky white foam: mp 64-65 °C. Rf (10: 1 CH2Cl2/MeOH) = 0.29.

Synthesis of N-Benzyl Threonine Analogues by Reductive Amination Example 4: Synthesis of (2S, 3R)-3-hydroxy-2-{[4-phenylphenyl)methyl]amino} butanehydroxamic acid (3). Reagent MW Eq. g/ml mmol 4-biphenylcarboxaldehyde 182.22 1.0 1. 104 g 6.06 L-Thr-OMe-HCl 169.61 1. 0 1.030 g 6.07 NaBH (OAc) 3 211.94 1.4 1. 800 g 8.49 Et3N 101.19 2.0 1. 70 mL 12.1 THF 25 mL Triethylamine (1.70 mL, 12.1 mmol) was added to a stirred suspension of L-threonine methyl ester hydrochloride (1.030 g, 6.07 mmol) and 4-biphenylcarboxaldehyde (1.104 g, 6.06 mmol) in THF (25 mL). After 20 min, NaBH (OAc) 3 was added and the suspension stirred for 20 h. The reaction was monitored by TLC (50: 1 DCM/MeOH, Rf=0. 4). The reaction mixture was quenched with saturated NaHCO3 (50 mL), extracted with EtOAc (2 x 120 mL), dried over MgS04, filtered and concentrated to give a yellow oil. Purification by silica gel chromatography (150 : 1 DCM/MeOH) afforded 1.220 g (67% yield, 98% pure) of (2S, 3R)-2-[(biphenyl-4-ylmethyl)-amino]-3-hydroxy-butyric acid methyl ester 2 as a pale yellow oil.

HPLC (260 nm, 34 min run) 14.2 min; LRMS (ES+) m/z 299.9 (C18H21NO3 +H requires 300.10).

Compound 3 was then formed by the addition of NH2OH in MeOH/NaOMe at 0°C, warming to ambient temparture of the period of several hours. LCMS MH+ 301.15.

General Methods for Making Phenyl-benzoic acids and Phenyl-benzoate esters (see Example 5 below) Suzuki Procedures Using Pd (dppi) CI2-DCM Catalyst and a THF/H20 Mixture Reagent MW EQ g/ml mmol BromoAreneWl ~300 1 100 mg-0. 33 Boronic Acid &num 2 - 1.2 - #0. 40 Na2C03 105.99 3 104 m #0. 99 Pd (dppf) Cl2 816.63 0.1-0. 2 27-54 mg-0. 033-0.066 THF (3) (sparged with argon for 5 min. ) 0.75 ml water (l) (sparged with argon for 5 min.) 0.25 ml Standard Procedure 1 eq aryl halide (1) was added to 1.2 eq. (2) and Pd (dppf) Cl2 in THF, followed by addition of water and stirred 8 hours at RT. Upon completion (usually over night), the reactions are diluted with ethyl acetate (5-10 ml) and water (1 ml). The organic layer is separated and washed with NaHCO3 (2x3 ml), water (lx3 ml), brine (lx3 ml), dried with Na2S04, filtered and concentrated in an 8 ml glass vial. The residue is dissolved in DMSO and injected on a preparatory HPLC reverse phase column to afford >80 % yield.

Suzuki Procedures Using Pd (dppf) Cl2-DCM Catalyst and DMF Solvent . Reagent MW EQ g/ml mmol BromoArene &num 1 #500 1 20 mg-0. 04 BoronicAcid&num 2-200 2-14 mg-0. 08 Pd (dppf) Cl2 816.63 0.25 10 mg-0. 01-0.02 TEA 101.19 5 28 pL-0. 2 DMF (dry & sparged with argon for 5 min. ) 0.5 ml Standard Procedure The haloarene 1 and boronic acid 2 were weighed out and placed in the reaction flask. The DMF was sparged with argon for 5-10 minutes, followed by TEA addition, and the reaction was lightly bubbled with argon. The solid Pd (dppf) Cl2 catalyst was added in one portion. The vial was flushed with argon, capped tight and stirred or shaken at-80 °C. Upon reaching completion (over night), the reaction was filtered and injected on a preparatory HPLC reverse phase column (80% yield).

Synthesis of Methyl DAP Analogues Example 5: 3- (R)-Amino-2- (S)- [ (4'-ethyl-biphenyl-4-carbonyl)-amino]-butyl-hydroxamic acid (8) Preparation of N-triphenylmethyl allo-threonine methyl ester (2).

'hic HCI Reagent MW EQ g/ml mmol H-allo-Thr-OMe-HCI (1) 169.7 1.2 2.0 g 12.0 Trt-Br 323.24 1.0 3.23 g 10.0 DIEA 129.25 3.0 5. 2 ml 30.0 CHCl3 (dry) 100 ml For similar procedures see: Righi, P.; Scardovi, N.; Marotta, E.; ten Holte, P.; Zwanenburg, B.

Organic Letters 2002,4 (4), 497-500.

A solution of trityl bromide (3. 2g, 10. 0mmol) in CHC13 (40ml) was added dropwise to a stirred solution of allo-threonine methyl ester HCl salt (1) (2. 0g, 12. 0mmol) and DIEA (5. 2ml, 30. 0mmol) in CHC13 (60ml) at rt under N2. The reaction could be followed by TLC eluting with EtOAc/Hex (40: 60) (Rf=0. 3). After stirring 12 h, the reaction was concentrated to a brown oil. The crude product was diluted with EtOAc (170ml) and washed with 0.2 N citric acid (2x50ml), water (2x50ml), brine (50ml), dried (Na2SO4), filtered and concentrated under reduced pressure to yield 3.73g (85% yield, . 95% pure) of a yellow solid.

HPLC (220nm, 41min. run) 30. 90 min.; HPLC (220nm, 17min. run) 14.86 min.; LCMS: LC (214nm) 3.06 min. , MS (ES+) m/z 376.2 (C24H25N03+H requires 376.18).

Preparation of 3-Azido-2-(S)-(trityl-amino)-butyric acid methyl ester (3).

2 3 Reagent MW Eq. g/ml mmol Trt-allo-Thr-OMe (2) 375.46 1.0 4. 08 g 10.88 PPh3 262.29 1.0 2. 85 g 10.88 DEAD (neat) 174.16 1. 6 2. 93 ml 17.82 DPPA 275.7 2.7 6. 40 ml 29.7 THF (dry) 50 ml For similar procedures see: Matsuda, A.; Yasuoka, J.; Sasaki, T.; Ueda, T. J. Med. Chem. 1991, 34,999-1002.

A solution of pure DEAD (2. 9ml, 17.8mmol) in THF (5ml) was added slowly dropwise to a stirred solution of trt-allo-threonine methyl ester (2) (4. 1g, 10. 9mmol) and PPh3 (2.9g, 10. 9mmol) in THF (40ml) at 0'C under'N2. After 3 min. , a solution of DPPA (6. 4ml, 29.7mmol) in THF (5ml) was added to the orange-yellow reaction solution at 0 °C. After 1 h, the reaction was allowed to warm to rt. After 40h, the reaction had reached completion by TLC (Hexane/DCM/EtOAc (64: 20: 16) (Rf=0. 6)). and LCMS. The yellow solution was concentrated to give 18g of crude material that was purified by column chromatography eluting with Hexane/EtOAc (88: 12) giving 3. 5g of 70% pure product after evaporation. The product was purified again (to remove trityl alcohol and a crotyl side- product formed during the reaction by elimination) by column chromatography eluting with Hexane/DCM/EtOAc (76: 20: 4) giving 1.65g (38% yield) of a pale yellow oil after concentration and drying in vacuo. Note that the trityl protecting group would hydrolyze when exposed to TFA while running the sample on HPLC.

Alternately, the reaction could be carried out in dry DCM. A reaction using 5.44g (14.5 mmol) of trt-allo-threonine methyl ester (2) in DCM (100ml) with PPh3 (3.8g, 14.5mmol), pure DEAD (3. 4ml, 21. 8mmol) in DCM (5ml) and DPPA (6. 3ml, 24. 0mmol) in DCM (10ml) were combined following the procedure above. After 3 days, the reaction did not progress further by TLC and LCMS.

After the same work up, 2.97g of the product was obtained in 51% yield.

HPLC (220nm, 41min. run) 40.5 min.; HPLC (220nm, 17min. run) 16.32 min. ; LCMS: LC (214nm) 3.7 min. , MS (ES+) m/z 401.2 (C24H25N302 +H requires 401.15).

Preparation of 2- (S)-Amino-3- (R)-azido-butyric acid methyl ester HCI Salt (4).

Reagent MW EQ g/ml mmol Trt-Azido-Thr-OMe (3) 400.47 1. 0 4.79 g 11.98 TFA 57 ml CHCl3 (dry) 3 ml A solution of Trt-Azido-Thr-OMe (3) (4.8g, 12.0mmol) was dissolved in a 95% TFA/DCM solution (60ml) at rt with stirring. After 2.5 h, the reaction was complete by LCMS. The bright yellow solution was diluted with 0.5 N aq. HCI (300ml). The aqueous layer was extracted with DCM (2x30ml) and then lyophilized to dryness. The white solid was dissolved in AcCN/water (50: 50) (100ml) and again lyophilized to dryness to produce a consistent powder and remove as much of the TFA as possible. The azido-Thr'product (4), 2.26g (97% yield, 95% pure) of a white solid, was obtained as the HCI salt.

HPLC (220nm, 41min. run) 7.91 min.; HPLC (220nm, 17min. run) 3.36 min ; LCMS: LC (214nm) 0.48 min. , MS (ES+) m/z 159.3 (C5H10N4O2 +H requires 159.08).

Preparation of 3- (R)-Azido-2- (S)- [ (4'-ethyl-biphenyl-4-carbonyl)-amino]-butyric acid methyl ester (6). Reagent MW EQ g/ml mmol Azido-Thr-OMe-HCI (4) 194.62 1.0 195 mg 1.0 Biphenyl Acid (5) 226.27 1.0 226 mg 1.0 HOBT 153 1.0 158 mg 1.0 EDC-HC1 191.17 1.3 249 mg 1.3 DIEA 129.25 2.5 0. 44 ml 2.5 DCM (dry) 10 ml A EDCHC1 (249mg, 1. 3mmol) was added to a stirred colorless solution of azido-Thr- OMe-HCI (4) (195mg, l. Ommol), HOBT (158mg, l. Ommol), 4'-Ethyl-biphenyl-4-carboxylic acid (5) (226mg, l. Ommol) and DIEA (0.44ml, 2. 5mmol) in DCM (10ml) at rt under N2. After 24 h, the reaction had reached completion by TLC (Hexane/EtOAc (60: 40) (Rf=0. 3) ) and LCMS. The reaction was evaporated under reduced pressure to a brown tar. The crude product was dissolved in EtOAc (100ml) and washed with 0.2N aq. HC1 (2x50ml), aq. sat. NaHCO3 (50ml), brine (50ml), dried (Na2S04), filtered and concentrated under reduced pressure to yield a crude brown solid. The crude material was further purified by column chromatography eluting with Hexane/EtOAc (70: 30) giving 245mg (67% yield) of pure product after evaporation and drying in vacuo.

HPLC (220nm, 41min. run) 33.87 min.; HPLC (220nm, 17min. run) 15.61 min; LCMS: LC (214run) 3.25min., MS (ES+) m/z 367.2 (C2oH22N403 +H requires 367.17).

Preparation of 3-(R)-Amino-2-(S)-1 (4'-ethyl-biphenyl-4-carbonyl)-amino]-butyric acid methyl ester (7).

Reagent MW EQ g/ml mmol Biphenyl Azido-Thr (6) 366.41 1.0 244 mg 0.67 10% Pd/C 200 mg H2 (gas) 12"balloon MeOH (dry) 10 ml A solution of biphenyl azido-Thr methyl ester (6) (244mg, 0. 67mmol) in MeOH (10ml) was made by sonicating until the milky precipitate cleared. After bubbling nitrogen through the reaction solution for 30 sec., 10% Pd/C was added in one portion. The reaction was stirred under nitrogen at RT. The reaction was exposed to aspirator vacuum to remove the nitrogen and then opened to the hydrogen gas at balloon pressure (~1 atm). The reaction stirred for 3h at which time the hydrogen was exchanged for nitrogen. The reaction was filtered through a pad of celite to remove the palladium.

The celite pad was washed with MeOH (30ml). The combined fractions of MeOH were evaporated under reduced pressure and dried in vacuo to give 225mg (99po yield) of pure produce (7) as a white solid.

HPLC (220nm, 17min. run) 10.79 min.; LCMS: LC (214nm) 2. 21 min., MS (ES+) m/z 341.2 (C2oH24N202 +H requires 341. 18).

Preparation of 3"Amino-2-(S)-[(4'-ethyl-biphenyl-4-carbonyl)-amino]-butyl-h ydroxamic acid (8) Reagent MW EQ g/ml mmol.

Amino-Thr-OMe (7) 340.42 1.0 225 mg 0. 66 H2NOH-HCI 69.49 10.0 460 mg 6.6 NaOMe 54. 02-12. 0-430 mg 7.92 MeOH (dry) 7 ml DCM (dry) 5 ml To a stirred suspension of biphenyl-amino-Thr methyl ester (7) (225mg, 0.6mmol) and hydroxylamine HC1 salt (460mg, 6. 6mmol) in MeOH (7ml) and DCM (5ml) was added fresh solid NaOMe powder (430mg, 7. 92mmol) in one portion. After stirring for 2 min. at rt under nitrogen, the pH of the reaction on wet pH paper was approximately 7-8. The suspension had change from larger particles of white solid to a finely-divided milky consistency. The pH of the reaction was checked after adding small portions of NaOMe (50-lOOmg) and allowing 2 min. for the reaction to equilibrate.

The pH of the reaction reached a stable 11-12 after the final portion of NaOMe was added (250mg total). The reaction was initiated at pH 11 and proceeded quickly. After 30 min. , the reaction reached 85% completion as determined by LCMS, and the reaction was placed in a-10 °C bath. The cold mixture filtered over fine filter paper on a Biichner funnel. The white residue was washed with MeOH (15ml). The organic fractions were collected and concentrated under reduced pressure to give crude product (750mg). The crude product (only one 150 mg portion) was dissolved in DMSO (lml), AcCN (100p1) and water (100pal), passed through a Teflon syringe filter, and the clear filtrate was injected on a preparative HPLC. The purification used a 20x50 mm Ultro 120 C18 column running a 22 ml/min 2% gradient (AcCN/water, 0. 1% TFA) for 16 min. The purified fractions were lyophilized to dryness.

The product as the TFA salt was dissolved in AcCN/water (50: 50) (5ml), 1N aq. HCl (1 equivalent) and lyophilized again to give 11.5 mg of white powder as an HCl salt (23% yield).

HPLC (220nm, 41min. run) 19.31 min.; HPLC (220nm, 17min. run) 9.39 min ; LCMS: « LC (214nm) 1.98 min. , MS (ES+) m/z 342.2 (Cl9H23N303 +H requires 342.17).

Synthesis of 4'Benzamide Biphenyl Threonine Hydroxamic Acid Example 6: Biphenyl-4, 4'-dicarboxylic acid 41- [ (3-Boc-amino-propyl)-amidel 4- [ ( (2R)-hydroxy- (lS)-hydroxycarbamoyl-propyl)-amide] (6), and Example 7: Biphenyl-4, 4'-dicarboxylic acid 4'-[(3-amino-propyl)-amide] 4-[((2R)-hydroxy-(1S)- hydroxycarbamoyl-propyl)-amide] (7) Synthesis of (2S, 3R)-2-amino-3- (phenylmethoxy)-N- (phenylmethoxy) butanamide (1) Procedure: To a suspension of benzylhydroxylamine hydrochloride (8. 310 g, 52.06 mmol), Boc-Thr (OBn)- OH (14.01 g, 45.28 mmol), EDCI (10.01 g, 52.21 mmol), and HOBt (6.90 g, 51.06 mmol) in CH2Cl2 (300 mL) at 0 °C was added diisopropylethylamine (28.3 mL, 162 mmol) with stirring. The cooling bath was removed after one hour and the reaction mixture stirred at ambient temperature for 20 h and was then diluted with CH2C12 (300 mL). The organic layer was washed with 1.0 M HCl (2 x 200 mL), sat. NaHCO3 (2 x 200 mL) and brine (200 mL), dried over MgSO4 and concentrated to give 14.5 g of a white solid. The crude solid was treated with a solution of trifluoroacetic acid (90 mL) in CH2CI2 (90 mL) and stirred for 2.5 h. The reaction mixture was concentrated by rotary evaporation and then diluted with CH2Cl2 (600 mL). The organic layer was washed with sat. NaHCO3 (2 x 200 mL), dried over MgS04 and concentrated to give a dark orange oil. Purification by silica gel chromatography (50: 1 CH2Cl2/MeOH) afforded (2S, 3R)-2-amino-3-(phenylmethoxy)-N-(phenylmethoxy) butanamide (A) (8.9 g, ) as a pale yellow oil. Rf (50: 1 CH2Cl2/MeOH on silica gel) = 0.2.

Preparation of (1S, 2R)-4'-(2-benzyloxy-1-benzylovcarbamoyl-propylcarbamoyl)-bip henyl4- carboxylic acid (3).

Reagent MW Eq. g/mL mmol Amine (1) 314.38 1.0 0.944 g 3.00 Dicarboxylic acid (2) 242.23 1.9 1. 360 g 5.61 BOP 442.3 1.5 2.007 g 4.54 DIEA 129.25 3.3 1.7 mL 9.76 DMF 200 mL To a suspension of 4, 4'-biphenyldicarboxylic acid 2 (1.360 g, 5.61 mmol) in DMF (180 mL) was added BOP (2.007 g, 4.54 mmol) and DIEA (1.7 mL, 9.8 mmol). A solution of (lS, 2R) -2-amino- 3, N-bis-benzyloxy-butyramide 1 (944 mg, 3.00 mmol) in DMF (20 mL) was added and the reaction stirred for 18 h. The solution was diluted with EtOAc (250 mL) and washed with 1.0 M HC1 (500 mL). The aqueous layer was extracted with EtOAc (250 mL) and the organic layers combined. The organic layer was washed with 1.0 M HCl (250 mL), dried over MgS04, and concentrated to give a crude yellow solid. Purification by silica gel chromatography (60: 1 CH2Cl2/MeOH) gave 210 mg (lS, 2R)-4'-(2-benzyloxy-l-benzyloxycarbamoyl-propylcarbamoyl)-bi phenyl4-carboxylic acid 3.

(13% yield) as a yellow solid. Rf= 0.80 (10: 1 CH2Cl21MeOH) ; LRMS (ES+) walz 539.1 (C32H30N206 + H requires 539. 22).

Preparation of biphenyl-4, 4'-dicarboxylic acid 4'- [(3-(Boc)-amino-propyl)-amide]-4-[(2R)- benzyloxy-(1S)-benzyloxycarbamoyl-propyl)-amide] (5).

Reagent MW Eq. g/mL mmol Biphenylcarboxylic acid (3) 538.59 1.0 0.200 g 0.371 Amine (4) 174.24 1.1 0.071 g 0.407 EDCI 191.71 1.1 0.078 g 0.407 HOBt 135.13 1.0 0.052 g 0.385 DIEA 129.25 2.7 180 µL 1.0 DMF 2 mL To a solution of biphenylcarboxylic acid 3 (200 mg, 0.371 mmol), EDCI (78 mg, 0. 407 mmol), and HOBt (52 mg, 0.385 mmol) in DMF (-2 mL) was added t-Butyl N- (3-aminopropyl) carbamate 4 (71 mg, 0.407 mmol) and DIEA (180 pal, 1.0 mmol). The reaction mixture was stirred 24 h, diluted with EtOAc (150 mL), washed with 1.0 M HCl (2 x 60 mL), saturated NaHCO3 (2 x 60 mL), Ha0 (3 x 60 mL), dried over MgS04 and concentrated to give a crude white solid. Purification by silica gel chromatography (25: 1 CH2Cl2/MeOH) afforded 194 mg (75% yield) of biphenyl-4, 4'-dicarboxylic acid 4'- [(3-(Boc)-amino-propyl)-amide]-4-[(2R)-benzyloxy-(1S)-benzyl oxycarbamoyl-propyl)-amide] 5 as a white solid. Rf = 0. 15 (50 : 1 CH2Cl2/MeOH) ; LRMS (ES+) mlz 695.2 (C40H46N4O7 + H requires 695.35).

Preparation of Biphenyl-4, 4'-dicarboxylic acid 4'-[(3-Boc-amino-propyl]-amide] 4-[((2R)- hydroxy-(1S)-hydroxycarbamoyl-propyl)-amide] (6).

Reagent MW Eq. g/mL mmol Biphenyl diamide (5) 694. 82 1.00 0. 190 g 0.273 Pd (OH) 2 (20%/C) 106.42 0.15 0.020 g 0.040 H2 (g) balloon THF 5. 0 mL MeOH 3. 0 mL A solution of dibenzyl-piotected threonine hydroxamic acid 5 (190 mg, 0.273 mmol) in THF (5 mL) and MeOH (3 mL) was charged with Pd (OH) 2 (20%/C, 20 mg, 0.04 mmol) and stirred under a hydrogen atmosphere (balloon pressure) forl6 h. The crude mixture was filtered through a plug of celite eluting with 2: 1 MeOH/THF (15 mL) and concentrated to give an orange syrup. Purification by silica gel chromatography (5: 1: 1 THF/MeOH/CH2Cl2 afforded 110 mg (78% yield) of biphenyl-4,4'- dicarboxylic acid 4'-[(3-Boc-amino-propyl)-amide] 4-[((2R)-hydroxy-(lS)-hydroxycarbamoyl-propyl)- amide] as a white foam, mp 75-77 °C. Rf = 0.20 (10: 1 CH2Cl2/MeOH) ; LRMS (ES+) m/z 515. 4 (C26H34N407 + H requires 515.26).

Preparation of Biphenyl-4, 4'-dicarboxylic acid 4'-[(3-amino-propyl)-amide] 4-[((2R)-hydroxy- (lS)-hydroxycarbamoyl-propyl)-amide] (7).

Reagent MW Eq. g/mL mmol Boc-protected amine (6) 514.57 1.00 0. 080 g 0.155 TFA 3.0 mL CH2C12 3. 0mL A flask containing Boc-protected amine 6 (80 mg, 0.155 mmol) was treated with 50% TFA/CH2Cl2 (6.0 mL) and stirred for 2.5 h. The reaction mixture was concentrated by rotary . evaporation to give a brown syrup. Purification by RP-HPLC (C18 column, CH3CN gradient 5-70%, 0. 1% TFA, UV analysis 300 rim, 36 min) and lyophilization of the collected fractions afforded 14 mg (21% yield) of biphenyl4, 4'-dicarboxylic acid4'-[(3-amino-propyl)-amide] 4-[((2R)-hydroxy-(lS)- hydroxycarbamoyl-propyl)-amide] as a white solid. LRMS (ES+) m/z 415.3 (C2lH26N405 + H requires 415.20) ; RP-HPLC (300 nm, 36 min run) 18.2 min.

Example 8: Synthesis of N- (2- (N-hydroxycarbamoy !) (2S)-2- { [4- (4- ethylphenyl) phenyl] carbonylamino} ethyl) acetamide (4) H Ac20, pyridine Ac) H2N-O-Trt Resin, O H HOXtN NFmoc U, D EA, NMP THF 0 H 1 2 T'- H NH N Ac 1. Piperidine, DMF (NH H 2. HATU, DIEA, NMP H (3' N"C. N I-N Fcmoc 0 N 4-Ethyl-biphenyl-0 H O H 4-carboxylic acid 3. TFA, water/ 4 Preparation of 3-Acetylamino-2- (9H-fluoren-9-ylmethoxycarbonylamino)-propionic acid (2). HAN N H2NX Ac20, pyridine Ac BO H THF. HO) lN'Fm°C 0 H) f H O H O H 2 Reagent MW EQ g/ml mmol Fmoc-DAP-H (1) 326.4 1.0 980 mg 3. 0 Acetic anhydride 102.09 1.5 425 uL 4.5 Pyridine 79.1 2.0 483 uL 6.0 THF 20ml Acetic anhydride in THF (5ml) was added to a cloudy mixture of Fmoc-DAP-H (1) (980mg, 3. 0mmol) and pyridine (483uL, 6. 0mmol) in THF (15ml) with stirring at rt. After 4 hours, the clear pale yellow solution had reacted completely by LCMS. The reaction was evaporated under reduced pressure. The residue was dissolved in EtOAc (150ml) and washed with 0. 1M NaHSO4 (50ml), water (50ml), sat. brine (50ml), dried with Na2S04, filtered and concentrated under reduced pressure to give 1.1 g of crude product as a white solid. The crude product was purified by prep. HPLC to give 0.99 g (90% yield) of acyl-DAP (2).

Preparation of (2-Acetylamino-l-hydroxycarbamoyl-ethyl)-carbamic acid 9H-fluoren-9-ylmethyl ester trityl resin (3). H H Ac N H2N-O-Trt Resin, NHsAc HATU, DIEA, NMP HO OI, H. Fmoc 4,. O. N OI. H. Fmoc 2 3 2 3 Reagent MW EQ g/ml mmol HzN-0-Trt Resin 1.0 120 mg 0.113 Fmoc-DAP (Ac) -H (1) 368.4 5.0 980 mg 0.564 HATU 380 5. 0 0. 146 g 0.564 DIEA 129.25 10.0 196 ul 1.13 NMP 1. 7 ml A solution of Fmoc-DAP (Ac) -H (1) (980mg, 0. 56mmol), HATU (0.146g, 0. 56mmol) in NMP (1. 7ml) was made. After 2 min. of shaking, the activated acid was added to the deprotected H2N-O-Trt Resin (120 mg, 0. 113mmol) at rt with shaking. [Deprotection of the Fmoc group from the resin was accomplished using 20% piperizine in DMF (4ml) for 2 hours twice. The resin was drained and washed with DMF (2x5ml) and DCM (2x5ml).] After shaking for 20 hours, the reaction was drained and washed with DMF (2x5ml) and DCM (2x5ml). The resin was dried and used as is in the next reaction.

Preparation of N-(2-5-hydroxycarbamoyl) (2S)-2-{[4-(4-ethylphenyl) phenyl] carbonylamino} ethyl) acetamide (4) Preparation of (2-Acetylamino-l-hydroxycarbamoyl-ethyl)-carbamic acid 9H-fluoren-9-ylmethyl ester trityl resin (3). Oqz H NH CNAc 1. Piperidine, DMF gNHo /Ac > H, l H Fmoc 2. HATU, DIEA, NMP H°N) uNJw O N 4-Ethyl-biphenyl-0 H H H 4-carboxylic acid I w 3 3. TFA, water 4 4 Reagent MW EQ g/ml mmol Fmoc-DAP (Ac)-Trt Resin (3) 1.0 120 mg 0.113 4'-Etbiphenyl 4-carboxy acid 226.3 5.0 91 mg 0.4 HATU 380 5.0 152 mg 0.4 DIEA 129.25 10.0 140 ul 0. 8 NMP 1. 0 ml The resin was treated with 20% piperizine in DMF (4ml) for 2 hours twice. The resin was drained and washed with DMF (2x5ml) and DCM (2x5ml). The resin was dried ira vacuo. A solution of 4'-Ethyl-biphenyl-4-carboxylic acid (9lmg, 0. 4mmol), HATU (152g, 0. 4mmol) in NMP (l. Oml) was made. After 2 min. of shaking, the activated acid was added to the deprotected H-DAP (Ac)-Trt resin (120 mg, 0. 113mmol) at rt with shaking. After shaking for 18 hours, the reaction was drained and washed with DMF (2x5ml) and DCM (2x5ml). The resin was dried in. vacuo. The product was cleaved from the resin through treatment with a solution of TFA (500uL), DCM (500uL) and water (50uL) for 25 min. The resin was filtered and washed with fresh DCM (2ml). The combined TFA and DCM fractions are evaporated under reduced pressure. The residue was diluted with CH3CN/water (1 : 1) (10ml) and lyophilized. The crude product was purified by prep. HPLC. The crude product was dissolved in DMSO (lml), passed through a Teflon syringe filter, and the clear filtrate was injected on a preparative HPLC. The purification used a 20x50 mm Ultro 120 C18 column running a 22 ml/min 2% gradient (AcCN/water, 0.1% TFA) for 16 min. The purified fractions were lyophilized to dryness.

The solid residue was lyophilized again from CH3CN/water (1: 1) (5ml) give 8. 6 mg of pure product (4) (-21% yield).

Example 9: Synthesis of 4'-Ethyl-biphenyl-4-carboxylic acid (1-hydroxycarbamoyl-2- methanesulfonylamino-ethyl)-amide (3) Preparation of 4'-Ethyl-biphenyl-4-carboxylic acid (2-amino-1-hydroxycarbamoyl-ethyl)-amide. trityl resin (2). Alloc NH2 NH 1. Dimethyl barbituric ( H ( 0 acid, Pd (PPh3) 4, ^"o, N (N VOIN, PPh a 2 1 Reagent MW EQ g/ml mmol Biphenyl-DAP (Alloc)-Trt Resin (1) 1.0 500 mg 0. 35 Dimethyl barbituric acid 156.14 10.0 600 mg 3.5 Pd (PPh3) 4 1135.6 1.0 438 mg 0.35 PPh3 262.3 2.0 202 mg 0.7 DCM 11. 0 ml Pd (PPh3) 4 (438mg, 0. 35 mmol) was added to a vial containing biphenyl-DAP (Alloc) -Trt Resin (1) (500mg, 0. 35mmol), Dimethyl barbituric acid (600mg, 3. 5mmol) and PPh3 (438mg, 0.35mmol) in DCM (l lml) at rt under argon. The mixture was sparged with argon and shaken for 16 hours. The bright yellow mixture was drained and washed with DMF (8x10ml) and DCM (8xl0ml). The resin was dried in vacuo to give the deprotected DAP resin 2.

Preparation of 4'-Ethyl-biphenyl-4-carboxylic acid (1-hydroxycarbamoyl-2-methane sulfonylamino-ethyl)-amide (3). o 0 o ; s, NH2 NH H O H w N) + 1. MsCI, Lutidine, DCM H (iro, N, ,,,) 0. HO'C. 0 H I. 2. TFA, water O H < 2. /. 3 / Reagent MW EQ g/ml mmol Biphenyl-DAP-Trt Resin (2) 1.0 160 mg 0.11 Methanesulfonyl chloride 114.55 10.0 85 uL 1.1 Lutidine 107. 16 15.0 190 uL 1.6 DCM 1. 5 ml Methanesulfonyl chloride (85uL, l. lmmol) was added to a mixture of deprotected DAP resin (2) (160mg, 0. 11mmol) and lutidine (190uL, 1. 6mmol) in DCM (1. 5ml). After shaking for 16 hours, the mixture was drained and washed with DMF (lOx2ml) and DCM (5x2ml). The product was cleaved from the resin through treatment with TFA/water (4: 1) (1. 5ml). After shaking for 45 min. , the TFA solution was collected from the resin by filtration, and the resin was washed with TFA (lml) and TFA/water (1 : 1) (10ml). The combined TFA fractions were concentrated under reduced pressure to a reddish-brown solid. The product, identified by LCMS, was purified by prep. HPLC using a 20x50 mm Ultro 120 C18 column running a 22 ml/min 4% gradient (AcCN/water,. 0. 1% TFA) for 16 min.

The purified fractions were lyophilized to dryness. The solid residue was lyophilized again from CH3CN/water (1: 1) (5ml) give 4 mg of pure product as a white solid (3) (#9% yield).

Example 10: Synthesis of 4'-Ethyl-biphenyl-4-carboxylic acid [2- (3, 3-dimethyl-ureido)-l- hydroxycarbamoyl-ethyl]-amide (3) (Continued from compound 2 of Example 9 above) °91-2- NH2 NH H 0 1. Dimethylcarbamyl H 0 o'N chloride, lutidine, DCM C. H 2. TFA, water p H -,-ou Reagent MW EQ g/ml mmol Biphenyl-DAP-Trt Resin (2) 1. 0 125 mg 0.096 Dimethylcarbamyl chloride 107.5 10.0 103 mg 0.96 Lutidine 107.16 20.0 225 uL 1 : 92 DCM 1. 5 ml Dimethylcarbamyl chloride (103mg, 0.96mmol) was added to a mixture of deprotected DAP resin (2) (125mg, 0. 096mmol) and lutidine (225uL, 1. 92mmol) in DCM (1. 5ml). After shaking at rt for 5 hours, the mixture was drained and washed with DCM (5x2ml), DMF (5x2ml) and DCM (5x2ml). The product was cleaved from the resin through treatment with TFA/water (4: 1) (1. 5ml).

After shaking for 45 min. , the TFA solution was collected from the resin by filtration, and the resin was washed with TFA/water (1: 1) (2ml). The combined TFA fractions were concentrated under reduced pressure to a reddish-brown solid. The product, identified by LCMS, was purified by prep.

HPLC using a 20x50 mm Ultro 120 C18 column running a 22 ml/min 4% gradient (AcCN/water, 0. 1 % TFA) for 16 min. The purified fractions were lyophilized to dryness. The solid residue was lyophilized again from CH3CN/. water (1: 1) (5ml) give 5 mg of pure product as a white solid (3) (~13% yield).

Example 11: Synthesis of 4'-Ethyl-biphenyl-4-carboxylic acid [2-(2-amino-ethylamino)-1- hydroxycarbamoyl-ethyl]-amide (2).

Reagent MW EQ g/ml mmol Biphenyl-DAP-hydroxamate (1) 327. 4 1.0 20 mg 0.096 Boc-amino-acetaldehyde 159.19 4.0 6.4 mg 0.4 NaBH3CN 62.84 10.0 3.1 mg 0.05 Acetic acid 60.05 20.0 6 uL 1.00 DCM 1. 5 mol NaBH3CN (3. 1mg, 0. 05mmol) followed by acetic acid (6uL, l. Ommol) were sequentially added to a stirred suspension of biphenyl-DAP-hydroxamate (1) (20mg, 0. 096mmol) and Boc-amino- acetaldehyde (6.4mg, 0. 4mmol) in MeOH (1. 5ml) in a 4 ml vial. The reaction was followed by LCMS. After stirring 12 hours, the cloudy reaction was only 50% complete. The reaction was concentrated under reduced pressure to a thick slurry that was dissolved in DMSO. The product was purified by prep. HPLC using a 20x50 mm Ultro 120 C18 column running a 22 ml/min 3% gradient (AcCN/water, 0.1% TFA) for 16 min. The purified fractions were lyophilized to dryness. The dried powder was dissolved in CH3CN/water (1 : 1) (lml) and 1M HC1 (700uL). After heating at 50 °C for 75 min. , the reaction mixture was again lyophilized to dryness to produce 7.1 mg of product (2) as a 2xHCl salt white powder (-17% yield).

Example-12 : Synthesis of N- (l- (N-hydroxycarbamoyl) (lS, 2R)-2-hydroxypropyl) [4- (2- phenylethynyl) phenyl] carboxamide Preparation of 4-Phenylethynyl-benzoic acid (3) Reagent MW EQ g/ml mmol Iodo-benzoate 1 262 1.0 20.0 g 76.34 Ethynyl-benzene 2 102 1. 1 8.56 g 83.96 PdCl2 (PPh3) 2 702 0.012 0.65 g 0.92 Cul 190 0.024 0. 35 g 1.83 TEA 101 1.5 16 ml 114.5 d=0.726 THF (dry & sparged with argon for 5 min. ) 110 ml The 4-iodo-benzoic acid methyl ester 1 (20. 0g, 76. 34mmol), ethynyl-benzene 2 (8.56g, 83. 96mmol), PdCl2 (PPh3) 2 (0.65g, 0.92mmol), and Cul (0.35g, 1. 83mmol) were mixed with THF (110ml) in a round bottom under argon. The dry THF was sparged with dry, oxygen-free argon for at least 5 min. immediately before use. The reaction was cooled to 10 °C and TEA (16ml) was added.

The cooling bath was removed and the reaction was stirred at RT under argon. After 2. 5h, the reaction was diluted with EtOAc (400 ml) and the solids were filtered off through a pad of celite. The organic filtrate was washed with 1M HCl (60ml), sat. aq. NaHCO3 (60ml), water (60ml), brine (60ml), dried with Na2S04, filtered and concentrated under reduced pressure. The crude solid methyl ester was dissolved in MeOH (400ml), 6M NaOH (30ml) and water (50ml). The reaction was stirred at 70 °C until a clear solution was formed (about lh). The reaction could be followed by LCMS. The reaction was cooled and diluted with water (500ml) and hexane (100ml). The pH was adjusted to pH 6-7. The white solid that formed was collected and washed with water (3x60ml) and hexane (3x60ml). The solid 3 was dried ira vacuo yielding 17.3g (approximately quantitative yield in 99% purity).

Preperation of 3-Hydroxy-2-(4-phenylethynyl-benzoylamino)-butyric acid methyl ester (4) Reagent MW EQ g/ml mmol 4-Phenylethynyl-benzoic acid (3) 222 1. 0 1. 55 g 7.0 Threonine methyl esterHCl 169.65 1.4 1. 66 g 9.8 HBTU 380 1.0 2. 66 g 7.0 DIEA 125.28 2.5 3. 05 ml 17.5 DMF 21 ml A solution of threonine (1.66g, 9. 8mmol) and DIEA (1. 53ml, 8.8mmol) in DMF (10ml) was added to a stirred solution of 4-phenylethynyl-benzoic acid 3 (1. 55g, 7.0mmol) and DIEA (1. 53ml, 8. 8mmol) in DMF (11ml) at rt. After 12 h, the reaction was diluted with EtOAc (300ml) and washed with 0. 5M HC1 (2x60ml), sat. aq. NaHCO3 (60ml), 50% diluted brine (60ml), sat. brine (60ml), dried with Na2S04, filtered and concentrated under reduced pressure. Upon drying in vacuo, 2.34g of white solid was obtained (approximately quantitative yield in 99% purity).

Preperation of N (2-Hydroxy-1-hydroxycarbamoyl-propyl)-4-phenylethynyl-benzam ide (5) Reagent MW EQ g/ml mmol Tolanoic-Thr-OMe (4) 340.42 1.0 2.34 g 7.0 H2NOH-HCl 69.49 10.0 4.81 g 70. 0 NaOMe 54.02 >11.0 >4.16 g >77.0 MeOH (dry) 50 ml DCM (dry) 30 ml A solution of tolanoic-Thr methyl ester (4) (2.34g, 7. 0mmol) in MeOH (20ml) and DCM (30ml) was added to a cooled (-10 °C bath) suspension of hydroxylamine HCl salt (4.81g, 70. 0mmol) and NaOMe (4.16g, 77. 0mmol) in MeOH (30ml). Follow reaction by LCMS. After stirring for 2 hours, the reaction seems to stall at 50% completion. Add an additional 1 equivalent of NaOMe (0.416g). After 3 hours, the reaction was 75% complete. Add an additional 0.5 equivalent of NaOMe (0. 21g). After 4 hours, the reaction was 90% complete. Add an additional 0.15 equivalent of NaOMe (0.064g) for a total of 12.65 equivalents of NaOMe. The pH of the reaction was between 11- 12 and had reacted about 95% completion. The reaction was diluted with EtOAc (500ml) and washed with sat. aq. NaHCO3 (2x60ml), 50% diluted brine (60ml), sat. brine (60ml), dried with Na2SO4, filtered and concentrated under reduced pressure. The residue was dissolved in minimal DMA. The product was purified by prep. HPLC using a reverse phase Ultro 120 C18 column running a 2% gradient (AcCN/water, 0. 1% TFA). The purified fractions were lyophilized to dryness. The product as the TFA salt was dissolved in AcCN/water (50: 50) (80mol), 1N aq. HC1 (13 equivalent) and lyophilized again to give 1.3 g of white powder in 55% yield and >97% purity.

Example 13: Synthesis of 3- (R)-Amino-2- (S)- (3-phenylethynyl-benzoylamino)-butyl-hydroxamic acid (10) Preparation of 3- (R)-Azido-2- (S)- (3-phenylethynyl-benzoylamino)-butyric acid methyl ester (9).

The synthesis of compound 4 is described above. The tolanyl compound (9) was made by the same procedures as for compound (6). The product (9) was obtained in 92% yield (952mg).

HPLC (220nm, 41min. run) 32. 64 min.; HPLC (220nm, 17min. run) 15.08 min LCMS : LC (214nm) 3.16 min. , MS (ES+) m/z 363.1 (C2oHl8N403 +H requires 363.14).

Preparation of 3-eR)-Amino-2-(S)-(3-phenylethynyl-benzoylamino)-butyl-hydro xamic acid (10) Reagent MW Eq. g/ml mmol Ammo-Thr-OMe (9) 362.38 1. 0 726 mg 2.0 PPh3 262. 29 1.0 526 mg 2.0 H2NOH-HCI 69.49 10.0 1.4 g 20.0 NaOMe 54.02 #12.0 1.3 g 24.0 THF (dry) 20 ml MeOH (dry) 20 ml Triphenylphosphine (526mg, 2. 0mmol) was added to a stirred solution of tolanyl-azido-Thr methyl ester (9) (726mg, 2. 0mmol) at rt. After 3 days the reaction reached completion as judged by TLC (EtOAc/Hex (2: 1) ) and LCMS. The reaction was concentrated under reduced pressure to give an ivory colored solid. The crude amino-phosphine was dissolved in MeOH (20ml) to give a pale yellow solution. To the solution of amino-phosphine was added sequentially hydroxylamine HCl salt (1.4g, 20. 0mmol) followed by fresh solid NaOMe powder (1.3g, 24. 0mmol) to make a milky pH 10 suspension. After 36 h, the reaction was complete by LCMS. The reaction was evaporated under reduced pressure to give a yellow solid that was dried in vacuo. The crude product (2.75g) was triturated with ether (3x50ml) to remove impurities (P (O) Ph3) and then was dissolved in abs. EtOH (120ml) with sonication for 15 min.. A fine white powder was suction filtered off, and the clear yellow ethanolic portion was concentrated to a small volume. The crude product was dissolved in DMSO (8ml) and purified by preparative HPLC (Ultro 120 C18 75x300mm column) running a gradient (AcCN/water, 0.1% TFA) from 5 to 70% for 55 min. The purified fractions were pooled together and lyophilized to dryness. The product as the TFA salt was dissolved in AcCN/water (50: 50) (100ml), IN aq. HC1 (1 equivalent) and lyophilized again to give 325 mg of light yellow powder as the HC1 salt (43% yield).

HPLC (220nm, 41min. run) 18.31 min.; HPLC (220nm, 17min. run) 9.11 min ; LCMS: LC (214nm) 1.91 min. , MS (ES+) m/z 338.1 (CloHIoN303 +H requires 338.14).

Synthesis of 4'-(N-Acylamino)-Tolan Dap Analogs Example 14: Synthesis of 4-({4-[(aminoacetyl) amino] phenyl}ethynyl)-N-[(1S)-1-(aminomethyl)-2- (hydroxyamino)-2-oxoethyl] benzamide Preparation of 2-N-Boc-amino-N- (4-iodo-phenyl)-acetamide (2).

Reagent MW Eq. g/ml mmol Boc-Gly-OH 175.19 1.00 1.752 g 10.0 4-Iodoaniline (1) 219.03 1.04 2.290 g 10.4 EDCI 191.71 1.04 1. 994 g 10.4 HOBt 135.13 1.00 1.351 g 10.0 DCM 18 rnL DMF 1 mL A solution of Boc-Gly-OH (1.752 g, 10.0 mmol) in DCM (18 mL) and DMF (1 mL) was treated with EDCI (1.994 g, 10.4 mmol) and HOBt (1. 351 g, 10.0 mmol). After stirring 15 min, 4- iodoaniline 1 (2.290 g, 10.4 mmol) was added and the reaction monitored by TLC (25: 1 DCM/MeOH (Rf= 0.6)). After 24 h the solution was diluted with EtOAc (250 mL), washed with 1.0 M HCl (3 x 100 mL), sat. NaHCO3 (3 x 100 mL), brine (3 x 100 mL), dried over MgS04, filtered and concentrated in vacuo to afford 2.900 g (77% yield) of a white solid.

Preparation of (2S)-3-N-Boc-amino- (4-ethynyl-benzoylamino)-propionic acid methyl ester (4).

Reagent MW Eq. g/mL mmol 4-Ethynylbenzoic acid (3) 146.14 1.0 0.910 g 6.22 H-Dap (Boc)-OMe-HCl 254.71 1.2 1.903 g 7. 47 EDCI 191.71 1.2 1.432 g 7.47 HOBt 135.13 1. 1 0.910 g 6.73 DIEA 129.25 3.2 3.5 mL 20.0 DMF 50 mL Triethylamine (3.5 mL, 20.0 mmol) was added to a stirred solution of 4-ethynylbenzoic acid 3 (910 mg, 6.22 mmol), H-Dap (Boc)-OMe hydrochloride (1.903 g, 7.47 mmol), EDCI (1.432 g, 7.47 mmol), and HOBt (910 mg, 6.73 mmol) in DMF (50.0 mL). After stirring 20 h, the reaction mixture was diluted with EtOAc (400 mL), washed with 1.0 M HCl (2 x 100 mL), saturated NaHCO3 (2 x 100 mL), Ha0 (4 x 100 mL), dried over MgS04, filtered and concentrated in vacuo to give 2.140 g (99% yield) of a tan solid, mp = 110-111 °C. LRMS (ES+) m/z 346.9 (Cl8H22N20s + H requires 347.10).

To a suspension of methyl (2S)-3- [ (tert-butoxy) carbonylamino]-2- [ (4- ethynylphenyl) carbonylamino] propanoate (4) (200 mg, 0. 577 mmol) and 2- [ (tert- butoxy) carbonylamino]-N- (4-iodophenyl) acetamide (2) (476 mg, 1.26 mmol) was added Et3N (350 , uL, 2.5 mmol). The solution was purged with a stream of N2 for several minutes and PdCl2 (PPh3) 2 (20 mg, 0.028 mmol) and CuI (10.6 mg, 0.055 mmol) were added. The reaction mixture was stirred at ambient temperature for 22 h and then concentrated by rotary evaporation. The crude black residue was chromatographed twice by silica gel chromatography (30: 1 CHzClz/MeOH) to give 285 mg (83%) of methyl (2S)-3- [ (tert-butoxy) carbonylamino]-2- ( {4- [2- (4- f 2- [ (tert- butoxy) carbonylamino] acetylamino} phenyl) ethynyl] phenyl} carbonylamino) propanoate (5) as a yellow foam.

To a solution of hydroxylamine hydrochloride (98 mg, 1.41 mmol) in MeOH (1.3 mL) at 0 °C was added 25 wt% NaOMe (460 mg, 2.13 mmol). The solution was stirred at 0 °C for 15 min and then charged with a solution of methyl (2S)-3-[(tert-butoxy) carbonylamino]-2-({4-[2-(4-{2-[(tert- butoxy) carbonylamino] acetylamino} phenyl) ethynyl] phenyl} carbonylamino) propanoate (4) (279 mg, 0.469 mmol) in THF (1.5 mL) and MeOH (0.6 mL). The reaction was stirred at 0 °C for 30 min and at room temperature for 2.5 h. The reaction mixture was diluted with 4: 1 CHCl3/iPrOH (50 ml) and washed with 0.1 M HCl (30 mL). The layers were separated and the aqueous layer extracted once more with 4 : 1 CHCls/iPrOH (30 ml). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The crude residue was suspended in 10 : 1 CH2Cl2/MeOH (4 mL), filtered, and washed with 50 : 1 CHzCIz/MeOH (2 mL) and Et20 (10 mL) to afford 180 mg (64%) of N- (4- {2- [4- (N- {l-(N-hydroxycarbamoyl) (l S)-2-[(tert-butoxy) carbonylamino] ethyl} carbamoyl) phenyl] ethynyl} phenyl)-2-[(tert-butoxy) carbonylamino] acetamide (6) as a white powder.

To an oven-dried flask containing N- (4- {2- [4- (N- {1- (N-hydroxycarbamoyl) (1S)-2- [ (tert- butoxy) carbonylamino] ethyl} carbamoyl) phenyl] ethynyl} phenyl)-2- [ (tert- butoxy) carbonylamino] acetamide (6) (130 mg, 0.218 mmol) was added 1 : 1 TFA/CH2C12 (2.5 mL).

The resulting pink solution was stirred for 2 h and concentrated to give a pink gum. The crude residue was rinsed with CH2Cl2 (4 mL), concentrated by rotary evaporation and dissolved in THF (2 mL) and MeOH (0.4 mL). A solution of 4 M HCl in dioxane (200 p. L) was added and the resulting precipitate filtered and washed with Et20 (10 mL) to afford 90 mg of 4-({4- [ (aminoacetyl) amino] phenyl} ethynyl)-N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2- oxoethyl] benzamide as a pale tan powder.

Reaction of Iodoaniline with Bromoacetyl Bromide 0 1. Br\J4Br 09 0 benzene, EtsN (1 eq) J H2N /i \N /i 2. morpholine (excess) H-0- 3 . O O _-. O o-^,) 0 ON-NH2 H i NH , Ho OH 3 Bromoacetyl bromide (175 1L, 2.00 mmol) was added dropwise over 5 minutes to a solution of 4-iodoaniline (438 mg, 2.00 mmol) and Et3N (280, ut, 2.00 mmol) in benzene (5 mL). The reaction was stirred 1 hour, treated with morpholine (1.0 mL, 11.5 mmol) and stirred overnight. The reaction mixture was diluted with EtOAc (200 mL), washed with aqueous 0.1 M KOH (50 mL), H20 (50 mL), dried over MgS04 and concentrated to give a yellow oil. Purification by silica gel chromatography (100: 1 CH2C12/MeOH) afforded 630 mg (91%) of N- (4-iodophenyl)-2-morpholin-4-ylacetamide as a waxy tan solid. This product was converted to analogues in a similar manner as Example l Zt.

Example A : Preparation of 4- [4- (6-Chloro-pyridin-3-yl)-buta-1, 3-diynyl]-benzoic acid methyl ester.

Reagent MW EQ g/ml mmol H-DAP (Boc)-OMe (1) 254 1.05 5.93 g 23.3 4-Iodo-benzoic acid 248 1.0 5.49 g 22.2 HOAT 136.1 1.02 3. 08 g 22. 6 EDC 191. 71 1.02 4.33g 22.6 DIEA 129.25 2.5 9. 7 ml 55.1 DMF 85 ml DIEA (9. 7ml, 55. 1mmol) was added to a stirred solution of 4-iodo-benzoic acid (5.49g, 22. 2mmol), HOAT (3.08g, 22. 6mmol), EDC (4.33g, 22. 6mmol) in DMF (85ml). After 2 min. , the H- DAP (Boc) -OMe (1) was added in one portion. After 12 hours, the reaction was found complete by LCMS. The reaction was diluted with EtOAc/hexane (1: 1) (500ml). The organic phase was washed with IN HCl (2x80ml), IN NaOH (2x80ml), water (2x80ml), sat. brine (80ml), dried with Na2SO4, filtered and concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (1: 1). The fractions with product were evaporated to give 9.3 g of product (3-tert-Butoxycarbonylamino-2- (4-iodo-benzoylamino)-propionic acid methyl ester) in 93% yield. This product was converted to analogues in a similar manner as the aforementioned Examples.

Example 15 : N- (l- (N-hydroxycarbamoyl) (lS, 2R)-2-hydroxypropyl) (4-12- [4- (morpholin-4- ylmethyl) phenyl] ethynyl} phenyl) carboxamide (5) Preparation of (2S, 3R)-2-l4-(4-formyl-phenylethynyl)-benzoylaminol-3-hydroxy-bu tyrie acid methyl ester (3). Reagent MW Eq. g/ml mmol Ethynylbenzene (1) 261.27 1.0 0.745 g 2.85 4-Iodobenzaldehyde (2) 232. 00 1.4 0.902 g 3.89 PdCl2 (PPh3) 2 701.89 0.03 0.070 g 0.10 Cul 190.44 0.06 0.034 g 0. 18 Et3N 101.19 2.3 0. 90 mL 6. 5 THF 50mL A solution of alkyne 1 (745 mg, 2.85 mmol), 4-iodobenzaldehyde 2 (902 mg, 3.89 mmol), and Et3N (900 1L, 6.5 mmol) in THF (50 mL) was purged with a stream of N2 for two minutes and then treated with PdCl2 (PPh3) 2 (70 mg, 0.10 mmol) and CuI (34 mg, 0.18 mmol). The reaction mixture was stirred 40 h, concentrated by rotary evaporation and purified by silica gel chromatography (40: 1 DCM/MeOH) to give 0.833 g (80% yield) of (2S, 3R)-2- [4- (4-formyl-phenylethynyl)-benzoylamind]- 3-hydroxy-butyric acid methyl ester 3 as a pale yellow powder, mp = 143-144 °C. Rf = 0.3 (25: 1 DCM/MeOH) ; LRMS (ES+) m/z 366.1 (C2lHlgNOs + H requires 366.13) ; HPLC (300 nm, 47 min) 15.3 min.

Preparation of (2S, 3R)-3-Hydroxy-2- [4- (4-morpholin-4-ylmethyl-phenylethynyl)- benzoylamino]-butyric acid methyl ester (4).

Reagent MW Eq. g/ml mmol Tolanylaldehyde (3) 365.38 1.0 0.822 g 2.25 Morpholine 87.12 1.3 0.260 mL 2.97 NaBH (OAc) 3 211.94 1.4 0.670 g 3.16 THF 15 ml Sodium triacetoxyborohydride (0.670 g, 3.16 mmol) was added to a solution of benzaldehyde 3 (0.822 g, 2.25 mmol) and morpholine (260 µL, 2.97 mmol) in THF (15 mL) under N2 atmosphere and the reaction monitored by TLC (25: 1 DCM/MeOH, Rf=0. 2). After stirring 4 h, the reaction mixture was quenched with saturated NaHCO3 (150 mL), extracted with EtOAc (3 x 100 mL), dried over MgS04, filtered and concentrated to give a yellow syrup. Purification by silica gel chromatography (35: 1 DCM/MeOH) afforded 0.844 g (86% yield) of 4 as a sticky white foam. Preparation of (2S, 3R)-N-(2-Hydroxy-1-hydroxycarbamoyl-propyl)-4-(4-morpholin-4 -ylmethyl- phenylethynyl)-benzamide (5).

Reagent MW Eq. g/ml mmol Methyl ester (4) 436.50 1. 0 0.829 g 1.90 NHxOH-HCl 69.49 3.0 0.400 g 5.76 NaOMe (25 wt%) 54.02 4.5 1. 860 g 8.60 MeOH 8 mL THF 3 mL Sodium methoxide (25 wt% in MeOH, 1.860 g, 8.60 mmol) was added to a stirred solution of hydroxylamine hydrochloride (400 mg, 5. 76 mmol) in anhydrous MeOH (5 mL) at 0 °C under N2 atmosphere. After stirring 20 min, a solution of methyl ester 4 (829 mg, 1.90 mmol) in 1: 1 MeOH/THF (6 mL) was added and the reaction mixture stirred at 0 °C for 1 h and at room temperature for 4 h. The reaction was quenched with 1.0 M HCl (6 mL), concentrated by rotary evaporation to remove organic solvents, and diluted with DMSO (4 mL). Analytical RP-HPLC (Cls column, CH3CN gradient 5-35%, 0.1% TFA, W analysis 300 mn, 16 min) indicated a purity of 85% for the crude product mixture. Purification by preparative RP-HPLC and lyophilization of the collected fractions gave 701 mg (81%) of 5 as a fluffy white solid. LRMS (ES+) m/z 438.1 (C24H27N3Os + H requires 438.20) ; RP-HPLC (300 nm, 16 min run) 8.7 min.

Resin Procedures for Synthesizing Tolanyl hydroxamates Example 16: Synthesis of 4-[(4-{[(benzylamino) acetyl] amino} phenyl) ethynyl]-N-{(lS, 2R) -2- hydroxy-1-[(hydroxyamino) carbonyl]propyl}benzamide -NHFmoc 1. Piperdine OtBu 1. Piperdine 2. HATU N OtBu p NHFmoc 2. HBTU O zozo J'OH OH FmocHN"llff OtBu OtBu _ H O OtBu _ H2N 6, N 11 N II, N O N 0 H ° H I PdCI2 (PPh3) 2, Cul, Et CH3CN, 22. h NHz OtBu H 0 zon 'O "\N w I NHz Lutidinia 0 H - \ Bromo Acylchloride Nt/NMP N) tl/ H OtBu . HzN ,"N 4@) H (O 80% TFA/H20 \ YNJk H 0 H 0 N H 0 H N J N \OH H 0 H 0 H O H 1. Coupling to Fmoc hydroxylamine resin The resin was pre-swelled by adding DCM and shaking for 30min. The resin was drained, 20% piperdine was added in DMF, the resin was shaken 1.25 hours, and finally drained and washed in 2xDMF and 2xDCM. After draining completely, 20% piperdine in DMF was added to attain cleavage in 1.25 hours. The resin was washed 4xDMF, 4xDCM and drained completely. In a separate flask, the amino acid (Fmoc-Thr tBu-OH, or Fmoc-DAP Boc-OH, 4 eq) was mixed, HATU (4 eq), DMF (60 ml) and Hunig's (8 eq) base were added and stirred for 2-3 min. The mixture was added to the resin and shaken 20-24 hours. Subsequently, the resin was drained and run with a standard wash (lxDCM, 4xDMF and 4xDCM). The Fmoc was removed from the amino acid by adding 20% piperdine in DMF and shaken 1.25 hours, drained, and given the standard wash (lxDCM, 4xDMF and 4xDCM).

2. Coupling of 4-iodobenzoic acid to Amino Acid resin A mixture of 4-iodobenzoic acid (4 eq), HBTU (4 eq), DMF (60 ml) was shaken for several minutes. Hunig's base (8 eq) was subsequently added and the mixture was shaken further for 2-3 min.

The pre-activated mixture was then added to the prepared Thr or DAP resin (Fmoc removed, 7. 5g, 5.775 mmol). The reaction is shaken 12-16 hours followed by the standard wash (IxDCM, 4xDMF and 4xDCM).

3. Alkyne coupling on Resin To the 4-iodobenzoic resin (4 g, 3.08 mmol) was added 4-aminophenylacetylene (3 eq), Pd (PPh3) 2Cl2 (0.04 eq), Cul (0.08 eq) and THF (purged with Argon). After mixing for 1 min. , TEA (4.5 eq) was added and the reaction was shaken 12 hours at RT under argon.

4. Aniline coupling with bromoacetyl chloride on Resin To aniline resin (4g, 3.08 mmol) was added DCM (30 ml) lutidine (10 eq) and shaken for 1 min. Bromoacetyl chloride (8 eq) in DCM (5 ml) was added slowly. After the addition, the slurry was shaken for 1.5 to 1. 75 hours. Subsequent draining and a wash with 2xDCM, 4xDMF and 4xDCM was then performed.

5. Displacement with amines on Resin To the bromoacetyl resin (125 mg), was added NMP (1.5 ml) followed by amine (0.2 g or ml, ie excess) and the slurry was shaken for 12-16 hours at RT. To neutralize the salt, TEA was added.

The imidazole was heated at 38 °C for 24 h (in the case of anilines, they were heated at 38 °C for 48 h). The reaction mixture was drained and washed 4xDMF and 4xDCM.

6. Cleavage from resin and deprotection of Thr tBu and DAP Boc The resin (125 mg) was soaked in TFA/water (80: 20 v/v) (1.5 ml) at RT for 45 min. Upon cleavage the solution was collected and the resin was washed with more TFA/water mixture (0.75 ml).

To the TFA/product solution was added acetonitrile/water solution (1 : 1 v/v, 10 ml) and pure water (2.5 ml). The mixture was frozen in liquid nitrogen for-15 min and lyophilized. The dry residue was dissolved in the acetonitrile/water solution (1: 1 v/v, 10 ml) again followed by addition of 1M aq. HCl (1.2 eq per basic nitrogen), frozen, and lyophilized to a powder.

Synthesis of 3'-Nitro-Tolan Threonine Hydroxamic Acid Example 17 : (1S, 2R)- N- (2-hydroxy-1-hydroxycarbamoyl-propyl)-4- (3-nitro-phenylethynyl)- benzamide i. 20% piperidine/DMF o ii-DIC, HOBt, DIEA O DCM, DMF, 36 h FmocHN NO""/\ O-', I w H N. O zizi Oh % 2 H 3 Preparation of (lS, 2R)-N-(2-tert-butoxy-1-hydroxycarbamoyl-propyl)-4-ethynyl-be nzamide on hydroxylamine 2-chlorotrityl resin (3).

Reagent MW Eq. g/mL mmol Fmoc-threonine/resin (1) 0. 70 mmol/g 1.0 0.522 g 0.365 4-Ethynylbenzoic acid (2) 146.14 3.0 0. 160 g 1.10 DIC 126.20 4.9 0.28 mL 1.79 HOBt 135.13 3.0 0.148 g 1.10 DIEA 129.25 6.3 0.40 mL 2. 30 DCM 1.0 mL DMF 3.0 mL The resin 1 (0.522 g, 0.365 mmol, 0.70 mmol/g) was swelled in DCM (5 mL) for 2 h and drained. The resin was treated with 20% piperidine in DMF (6 mL) for 1 hour, washed with DMF (4 x 6 mL) and DCM (4 x 6 mL) and drained completely. In a separate flask, 4-ethynylbenzoic acid 2 (0.160 g, 1.10 mmol), DIC (0.280 mL, 1.79 mmol), HOBt (0.148 g, 1.10 mmol) and DIEA (0.4 mL, 2.30 mmol) were dissolved in DCM (1 mL) and DMF (4 mL), stirred 15 min and added to the resin.

After shaking for 36 h, the mixture was drained, washed with DMF (4 x 6 mL) and DCM (4 x 6 mL) and dried in vacuo to give 0.495 g of a yellow resin.

Preparation of (1S, 2R)-N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-4-(3-nitro-pheny lethynyl)- benzamide (5).

Reagent MW Eq. g/mL mmol Alkyne on resin (3) 0.70 mmol/g 1.0 100 mg 0.070 l-Iodo-3-nitrobenzene (4) 249.01 5.0 87.1 mg 0.350 PdCl2 (PPh3) 2 701.89 0.2 10.0 mg 0.014 Cul 190.44 0.5 7.0 mg 0.036 Et3N 101.19 15 150, uL 1.10 DMF 1.5 mL Resin 3 (100 mg, 0.070 mmol) was swelled in DCM (2 mL) for 1 h and drained. A solution of 1-iodo-3-nitrobenzene 4 (87.1 mg, 0.350 mmol) and Et3N (150 p, L, 1.10 mmol) in DMF (1.5 mL) was purged with a stream of N2 bubbles for two minutes and added to the resin. After mixing for 5 min, PdCl2 (PPh3) 2 (10. 0 mg, 0.014 mmol) and CuI (7.0 mg, 0.036 mmol) were added and the mixture shaken for 26 h. The resin was drained, washed with DMF (3 x 2 mL), DCM (3 x 2 mL) and cleaved with 10% TFA/DCM (1.5 mL) for 20 min. The solution was collected and the resin was rinsed with additional 10% TFA/DCM (1.0 mL). The cleavage fractions were combined, treated with neat TFA (2.0 mL), stirred for 1 h at rt and concentrated by rotary evaporation to give a crude brown residue.

Purification by RP-HPLC (Cl8 column, CH3CN gradient 5-65%, 0.1% TFA, UV analysis 300 nm, 28 min) and lyophilization of the collected fractions afforded 6.0 mg (22% yield) of (1S, 2R)- N- (2- hydroxy-l-hydroxycarbamoyl-propyl)-4- (3-nitro-phenylethynyl)-benzamide as a white foam. LRMS (ES+) m/z 384.2 (Cl9Hl7N306 + H requires 384. 15) ; RP-HPLC (300 nm, 28 min run) 15.2 min.

Synthesis of 4'-Trifluoromethoxy-Tolan Dap Hydroxamic Acid Example 18 : (1S)-N-(2-amino-1-hydroxycarbamoyl-ethyl)-4-(4-trifluorometh oxy- phenylethynyl) -benzamide (5) NHBoc i. 20% piperidine/DMF NHBoc ,) NrtDOC.. H ii. DIC, HOBT, DIEA H N,, DCM, DMF, 36 h NJN'OQ FmocHN O I i H 0 \==/OH" ou 2 Preparation of (lS)-N-(2-(Boc)-amino-l-hydroxycarbamoyl-ethyl)-4-ethynyl-be nz-amide on hydroxylamine 2-chlorotrityl resin (3).

Reagent MW Eq. g/mL mmol Fmoc-Dap/resin (1) 0. 70 mmol/g 1.0 1. 330 g 0. 931 4-Ethynylbenzoic acid (2) 146.14 3.0 0.408 g 2.793 DIC 126.20 4.8 0.70 mL 4.470 HOBt 135.13 3.0 0.377 g 2.793 DIEA 129.25 6.2 1. 0 mL 5.7 DCM 10. 0 mL DMF 2. 0 mL The resin 1 (1.330 g, 0.931 mmol, 0.70 mmol/g) was swelled in DCM (15 mL) for 2 h and drained. The resin was treated with 20% piperidine in DMF (20 mL) for 1 hour, washed with DMF (3 x 15 mL) and DCM (3 x 15 mL) and drained completely. In a separate flask, 4-ethynylbenzoic acid 2 (0.408 g, 2.793 mmol), DIC (0.70 mL, 4.470 mmol), HOBt (0.377 g, 2.793 mmol) and DIEA (1.0 mL, 5.7 mmol) were dissolved in DCM (10 mL) and DMF (2 mL), stirred 15 min and added to the resin.

After shaking for 36 h, the mixture was drained, washed with DMF (3 x 15 mL) and DCM (3 x 15 mL) and dried in vacuo to give 1.290 g of a yellow resin.

Preparation of (lS)-N-(2-amino-1-hydroxycarbamoyl-ethyl)-4-(4-trifluorometh oxy- phenylethynyl)-benzamide (5).

Reagent MW Eq. g/mL mmol Alkyne on resin (3) 0. 70 mmol/g 1.0 120 mg 0.084 4-CF30-iodobenzene (4) 287.99 4.0 96.8 mg 0.336 - PdCl2 (PPh3) 2 701. 89. 0. 3 18. 0 mg 0.025 Cul 190.44 0.5 8.0 mg 0.042 Et3N 101. 19 13 150 LL 1.10 DMF 2.0 mL Resin 3 (120 mg, 0.084 mmol) was swelled in DCM (2 mL) for 1 h and drained. A solution of 4-(trifluoromethoxy)iodobenzene 4 (96.8 mg, 0.336 mmol) and Et3N (150 µL, 1.10 mmol) in DMF (2.0 mL) was purged with a stream of N2 bubbles for two minutes and added to the resin. After mixing for 5 min, PdCl2 (PPh3) 2 (18.0 mg, 0.025 mmol) and CuI (8.0 mg, 0.042 mmol) were added and the mixture shaken for 24 h.. The resin was drained, washed with DMF (3 x 2 mL), DCM (3 x 2 mL) and cleaved with 10% TFA/DCM (2.0 mL) for 20 min. The solution was collected and the resin was rinsed with additional 10% TFA/DCM (1.0 mL). The cleavage fractions were combined, treated with neat TFA (3.0 mL), stirred for 1 h at rt and concentrated by rotary evaporation to give a crude brown residue. Purification by RP-HPLC (Ci8 column, CH3CN gradient 5-55%, 0.1% TFA, UV analysis 300 nm, 28 min) and lyophilization of the collected fractions afforded 9.0 mg (25% yield) of (1S)-N- (2- amino-l-hydroxycarbamoyl-ethyl)-4- (4-trifluoromethoxy-phenylethynyl)-benzamide as a white solid.

LRMS (ES+) m/z 408.0 (ClgHl6F3N304 + H requires 408. 11); RP-HPLC (300 nm, 28 min run) 18.0 min.

Example 19: Synthesis of N- (l- (N-hydroxycarbamoyl) (lS, 2R)-2-hydroxypropyl) [4- (4- phenylbuta-1, 3-diynyl) phenyl] carboxamide Reagent MW EQ g/ml mmol Dibromovinylbenzoic acid (2) 320 1.0 5.76 g 18. 0 Ethynyl-benzene 102 1.4 2.57 g 25.2 Pd2dba3 915 0.01 164 mg 0.18 (1% cat. ) TMPP 352 0.04 253 mg 0.72 (4%) TEA 101 3.0 7. 5 ml 54.0 DMF 60 ml degassed with argon The 4- (2, 2-Dibromo-vinyl)-benzoic acid methyl ester (2) was made by the method of Wang Shen and Le Wang in J. Org. Chem. 1999, 64, 8873-8879.

A solution of 4-(2,2-dibromo-vinyl)-benzoic acid methyl ester (2) (5.76g, 18. 0mmol), ethynyl- benzene (2.57g, 25. 2mmol), Pd2dba3 (164mg, 0. 18mmol), tris (4-methoxyphenyl) phosphine (TMPP) (253mg, 0. 72mmol) were dissolved in argon sparged (5 min. ) DMF (60ml). The reaction was sparged with argon for 1 min. TEA (7. 5ml, 54. 0mmol) was added to the stirred reaction mixture that was then heated under argon at 85 °C for 3.5 hours. The reaction was found complete by LCMS. The reaction was cooled to rt and diluted with EtOAc/hexane (1: 1) (300ml). The organic phase was washed with 1M HC1 (2x50m1), 1M NaOH (3x50ml), water (2x50ml), sat. brine (50ml), dried with Na2S04, filtered and concentrated under reduced pressure to obtain 5.25g of crude product as an oil. The oil was treated with approximately 20 ml of a solution of 20% EtOAc/hexane that was heated to dissolve the residue. The walls of the flask were washed with the 20% EtOAc/hexane solution (5ml) that upon cooling gave 1.45 g-of pure product (31% yield) as a white solid. The balence of the crude reaction product was purified by flash chromatography using EtOAc (8%) /hexane as eluant. The pure fractions were evaporated and dried in vacuo to give addition product typically 25-30% addition yield.

4- (4-Phenyl-buta-1, 3-diynyl) -benzoic acid methyl ester (4) was made according to the method of Wang Shen and Sheela A. Thomas in Org. Lett. 2000,2 (18), 2857-2860.

Preparation of 4- (4-Phenyl-buta-1, 3-diynyl)-benzoic acid (5) A 3M aq. solution of NaOH (20ml) was added to a stirred solution of methyl ester 4 (1.45g, 5. 6mmol) in MeOH (100ml) at rt. The reaction solution was heated to reflux for 45 min. until the reaction turned clear. All of the starting material was gone by TLC and HPLC. The reaction was cooled to rt and some MeOH (-50ml) was removed by evaporation under reduced pressure. Water (100ml) was added to the mixture. Conc. HC1 was added dropwise to the stirred solution until acidic by pH paper (pH2). The white precipitate that formed was collected by suction filtration. The solid was washed with water (3x20ml) and hexane (2x20ml) to give after drying 1.35 g of product acid 5 in 99% yield.

Subsequent conversion of compound 5 to compound 7 was performed according to the method described in Example 12 for the synthesis of N (2-Hydroxy-l-hydroxycarbamoyl-propyl)-4- phenylethynyl-benzamide (compound 5). LCMS MH+ 363.13.

Example B: Synthesis of N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2-oxoethyI]-4- [4- (4- aminophenyl) buta-1, 3-diynyl] benzamide Preparation of 2- {4- [4- (4-Amino-phenyl)-buta-1, 3-diynyl]-benzoylamino}-3-tert- butoxycarbonylamino-propionic acid methyl ester (2).

Reagent MW EQ g/ml mmol H-DAP (Boc) -OMe 254 1. 05 5. 12 g 20.1 1, 3-diynyl benzoic acid (1) 261. 3. 1.0 5. 0 g 19.1 HOBT 135.1 1.05 2. 72 g 20.1 EDC 191.71 1.05 3. 85 g 20.1 DIEA 129.25 3.0 10. 5 ml 60.3 DMF 80 ml DIEA (10. 5ml, 60. 3mmol) was added to a stirred solution of 4- [4- (4-Amino-phenyl)-buta-1, 3- diynyl] -benzoic acid (1) (5. 0g, 19. 1mmol), HOBT (2.72g, 20. 1mmol), EDC (3.85g, 20. 1mmol) in DMF (80ml). After 2 min., the H-DAP (Boc)-OMe was added in one portion. After 12 hours at rt, the reaction was found complete by LCMS. The reaction was diluted with EtOAc/hexane (4: 1) (500ml).

The organic phase was washed with 1N NaOH (2x80ml), water (2x80ml), sat. brine (80ml), dried with Na2S04, filtered and concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (4: 1). The fractions with product were evaporated to give 8.02 g of product in 91% yield.

Subsequent conversion of compound 2 to the final hydroxamic acid (for example, Example 892) was performed according to the method described in Example 12 for the synthesis of N-(2-Hydroxy-l- hydroxycarbamoyl-propyl)-4-phenylethynyl-benzamide (compound 5). Synthesis of 4- (Buta-1, 3-diynyl) -benzoic Acid (4) for making 1,3-diynyl analogues (such as Example 20 below) Preparation of 4- (4-trimethylsilanyl-buta-1, 3-diynyl)-benzoic acid methyl ester (3).

Reagent MW Eq. g/ml mmol Methyl 4-iodobenzoate (2) 262. 04 1.0 4. 5long 17.2 Trimethylsilylbutadiyne (1) 122.24 2.5 5. 240 g 42.8 PdCl2 (PPh3) 2 701. 89 0.04 0.483 g 0.690 Cul 190.44 0.08 0.262 g 1.37 Et3N 101.19 3.0 7. 2 mL 52.0 CH3CN 50 mL A solution of methyl 4-iodobenzoate 2 (4. 510 g, 17.2 mmol), PdCl2 (PPh3) 2 (483 mg, 0.690 mmol), and CuI (262 mg, 1.37 mmol) in CH3CN (50 mL) was cooled to 0 °C under N2 atmosphere in the absence of light. Triethylamine (7.2 mL, 52.0 mmol) was added, followed by trimethylsilyl-1,3- butadiyne 1 (5.240 g, 42.8 mmol) and the reaction stirred 3 h at 0 °C and 30 h at ambient temperature.

Removal of solvent by rotary evaporation afforded a crude black residue that was purified by silica gel chromatography (95: 5 hexanes/EtOAc) to give 3.450 g (79% yield) of 4- (4-trimethylsilanyl-buta-1, 3- diynyl)-benzoic acid methyl ester 3 as a brown solid, mp = 67-68 °C, Preparation of 4-(buta-1, 3-diynyl) -benzoic acid (4).

Reagent MW Eq. g/ml mmol Methyl ester (3) 252.34 1.0 3.420 g 13.5 KOH 56.11 4.9 3. 700 g 65.9 H20 10 mL THF 26 mL Potassium hydroxide (3.700 g, 65.9 mmol) was dissolved in Ha0 (10 mL) and added to a solution of 4- (4-trimethylsilanyl-buta-1, 3-diynyl)-benzoic acid methyl ester 3 (3.420 g, 13.5 mmol) in THF (26 mL) in the absence of light. After stirring 16 h, the reaction was quenched with 1.0 M HC1 (120 mL) and the resulting precipitate was filtered, washed with 1: 1 hexanes/benzene (150 mL) and dried in vacuo to afford 2.100 g (91% yield, 98% pure) of 4-(buta-1,3 diynyl)-benzoic acid 4 as a brown solid, mp > 230 °C. Although diyne 4 was found to be unstable at room temperature it could be stored for several weeks at 0 °C with only small amounts of decomposition observed by TLC. Rf = 0.2 (4: 1 Hexanes/EtOAc) ; HPLC (300 nm, 28 min run) 16.0 min; LRMS (ES+) m/z 171.0 (CsIH602 + H requires 171.04).

Synthesis of a 3'-Nitrophenyl-Diacetylenic-Dap Hydroxamic Acid Example 20: N- (l- (N-hydroxycarbamoyl) (lS)-2-aminoethyl) {4- [4- (3-nitrophenyl) buta-1, 3- diynyl] phenyl} carboxamide (6) i. 20% piperidine/DMF/H FmocHN H, ii. Fmoc-Dap (Boc)-OH FmocHN N'O 1 HATU, DIEA, DMF 2t o 1 2 i. 20% piperidine/DMF 0 NHBoc H ii. EDCI, HOBt, DIEA DCM, DMF, 36 h N N10 H 0 O/ 3 H NH2 NU2 oh H 0 2 02N < H O 6 PdCI2 (PPh3) 2, Cul \/6 Et3N, DMF, rt, 36 h i TFA, DCM NO2 Preparation of Fmoc-Dap (Boc)-NHOH on hydroxylamine 2-chlorotrityl resin (2). NHBoc i. 20% piperidine/DMF H FmocHN' O ii. Fmoc-Dap (Boc)-OH FmocHN N'O HATU, DIEA, DMF 2 o Reagent MW Eq. g/mL mmol Hydroxylamine resin (1) 0. 77 among 1.0 3.288 g 2.53 Fmoc-Dap (Boc) -OH 426.47 3.0 3.175 g 7.44 HATU 380.25 3.0 2.829 g 7.44 DIEA 129.25 10.0 4.3 mL 24.7 DMF 35 mL A suspension of N-Fmoc-hydroxylamine 2-chlorotrityl resin (3.288 g, 2.53 mmol, 0.77 mmoUg, Novabiochem) in DCM (40 mL) was shaken for 2 h and drained. The resin was treated with 20% piperidine in DMF (40 mL) for 1 hour, washed with DMF (2. x 40 mL), treated a second time with 20% piperidine in DMF (40 mL), washed with DMF (3 x 40 mL) and DCM (3x 40 mL) and drained completely. In a separate flask, Fmoc-Dap (Boc)-OH (3.175 g, 7.44 mmol), HATU (2.829 g, 7.44 mmol) and DIEA (4.3 mL, 24.7 mmol) were dissolved in DMF (35 mL), stirred three minutes and added to the resin. After shaking for 48 h, the mixture was drained, washed with DMF (4 x 40 mL) and DCM (4 x 40 mL) and dried in vacuo to give 3.530 g of a yellow resin.

Preparation of (S)-N- (2-N-Fmoc-amino-l-hydroxycarbamoyl-ethyl)-4-buta-1, 3-diynyl- benzamide on hydroxylamine 2-chlorotrityl resin (4). i. 20% piperidine/DMF NHBoc NHBoc ii. EDCI, HOBt, DIEA O H DCM, DMF, 36 h N' N FmocHN. N' \H O 3 H zizi Reagent MW Eq. g/mL mmol Fmoc-Dap (Boc)/resin (2) 0. 71 mmol/g 1.0 3.530 g 2.53 Butadiynyl benzoic acid (3) 170.16 2.5 1.076 g 6.32 EDCI 191.71 3.0 1.457 g 7.60 HOBt 135. 13 3.0 1. 048g 7.75 DIEA 129. 25 5.0 2.2 mL 12. 6 DCM 25 mL DMF 5 mL The resin 2 (3.530 g, 2.53 mmol, 0.71 mmol/g) was swelled in DCM (40 mL) for 2 h and drained. The resin was treated with 20% piperidine in DMF (40 mL) for 1 hour, washed with DMF (4 x 40 mL) and DCM (4 x 40 mL) and drained completely. In a separate flask, 4-buta-1, 3-diynyl- benzoic acid 3 (1.076 g, 6.32 mmol), EDCI (1.457 g, 7.60 mmol), HOBt (1.048 g, 7.75 mmol) and DIEA (2.2 mL, 12.6 mmol) were dissolved in DCM (25 mL) and DMF (5 mL), stirred 45 min and added to the resin. After shaking for 48 h, the mixture was drained, washed with DMF (4 x 40 mL) and DCM (4 x 40 mL) and dried in vacuo to give 3. 35 g of a pale brown resin. Preparation of (S)-N- (2-amino-1-hydroxycarbamoyl-ethyl)-4- [4- (3-nitro-phenyl)-buta-1, 3- diynyl]-benzamide (6). BOC NEZ ON 1 H > i. I 5 NNHOH NN\O I i H O Av O PdCI2 (PPh3) 2, Cul // Et3N, DMF, rt, 36 h ii. TFA, DCM NOz Reagent MW Eq. g/mL mmol Diacetylene on resin (4) 0. 77 mmol/g 1.0 176 mg 0.135 1-Iodo-3-nitrobenzene (5) 249. 01 3.5 118 mg 0.474 PdCI2 (PPh3) 2 701 : 89 0.07 6.0 mg 0.009 Cul 190.44 0.38 10.0 mg 0.052 Et3N 101.19 10.6 200 LL 1.43 DMF 3. 0 niL Resin 4 (176 mg, 0.135 mmol) was swelled in DCM (3 mL) for 1 h and drained. A solution of 1-iodo-3-nitrobenzene 5 (118 mg, 0.474 mmol) and Et3N (200 µL, 1.43 mmol) in DMF (3.0 mL) was purged with a stream of N2 bubbles for two minutes and added to the resin. After mixing for 5 min, PdCl2 (PPh3) 2 (6.0 mg, 0.009 mmol)'and CuI (10.0 mg, 0.052 mmol) were added and the mixture shaken for 36 h. The resin was drained, washed with DMF (4 # 3 mL), DCM (4 x 3 mL) and cleaved with 10% TFA/DCM (2 mL) for 20 min. The solution was collected and the resin was rinsed with additional 10% TFA/DCM (2 mL). The cleavage fractions were combined, treated with neat TFA (4.0 mL), stirred for 1 h at rt and concentrated by rotary evaporation to give a crude brown residue.

Purification by RP-HPLC (C1$ column, CH3CN gradient 5-65%, 0.1% TFA, UV analysis 300 nm, 30 min) and lyophilization of the collected fractions afforded 12.0 mg (22%) of 470 as a white solid.

LRMS (ES+) m/z 392. 9 (C2oHi6N405 + H requires 393.11) ; RP-HPLC (300 nm, 30 min run) 14.9 min.

Synthesis of 4'-Benzamide Diacetylene Dap Hydroxamic Acid Example 21: N- ( (2S)-amino-1-hydroxycarbamoyl-ethyl)-4- {4- [4- (2-amino-ethylcarbamoyl)- phenyl]-buta-1, 3-diynyl} -benzamide (3) Preparation of N- ( (2S)-amino-l-hydroxycarbamoyl-ethyl)-4-14- [4- (2-amino-ethylearbamoyl)- phenyl]-buta-1, 3-diynyl}-benzamide (3) Reagent MW Eq. g/mL mmol Alkyne on resin (1) 0. 77 mmol/g 1.0 145 mg 0. 111 4-Ethynylbenzamide (2) 430.54 2.6 124 mg 0.288 PdCl2 (PPh3) 2 701.89 0.3 21 mg 0.030 Cul 190.44 1.0 22 mg 0.110 Et3N 101.19 6. 5 100 µL 0.72 DMF 2.0 mL Resin 1 (145 mg, 0.111 mmol) was swelled in DCM (2 mL) for 1 h and drained. A solution of 4-ethynylbenzamide 2 (124 mg, 0.288 mmol) and Et3N (100 1L, 0.72 mmol) in DMF (2.0 mL) was added and the resin agitated for 5 min. A mixture of PdCl2 (PPh3) 2 (21 mg, 0.030 mmol) and CuI (22 mg, 0.110 mmol) was added and the resin was agitated for 60 h. The resin was drained, washed with DMF (3 x 2 mL), DCM (3 x 2 mL) and cleaved with 10% TFA/DCM (1.5 mL) for 20 min. The solution was collected and the resin was rinsed with additional 10% TFA/DCM (1.0 mL). The cleavage fractions were combined, treated with neat TFA (2 : 0 mL), stirred for 1 h at rt and concentrated by rotary evaporation to give a crude brown residue. Purification by RP-HPLC (Cl8 column, CH3CN gradient 5-55%, 0. 1% TFA, UV analysis 300 nm, 26 min) and lyophilization of the collected fractions afforded 2.6 mg (5% yield) of N-((2S)-amino-1-hydroxycarbamoyl-ethyl)-4-{4-[4- (2-amino-ethylcarbamoyl)-phenyl]-buta-1, 3-diynyl}-benzamide. LRMS (ES+) m/z 434.0 (C23H23N504 + H requires 434.19) ; RP-HPLC (300 nm, 26 min run) 15.3 min.

Synthesis of N- [4-Butadiynyl-benzoyl]-Thr (tBu) on Resin (Continued to make Examples 22 and 23) i. 20% piperidine/DMF FmocHN., Fmoc-Thr (OtBu)-OH FmocHN$fNsos 2 HATU, DIEA, DMF O i. 20% piperidine/DMF O O ii. EDCI, HOBt, DIEA JLXX N » DCM, DMF, 36 h i H O 0 H 3 H 3 3 Preparation of (2S, 3R)-2-N-Fmoc-amino-3-tert-butoxy-N-hydroxy-butyramide on hydroxylamine 2-chlorotrityl resin (2). i. 20% piperidine/DMF 9° FmocHN,, Fmoc-Thr (OtBu)-OH FmocHN NO I HATU, DIEA, DMF . Reagent MW Eq. g/mL mmol Hydroxylamine resin (1) 0. 77 mmoUg 1.0 3. 188 g 2.45 Fmoc-Thr (tBu)-OH 397.50 3. 0 2. 927 g 7.36 HATU 380.25 3.0 2. 798 g 7.36 DIEA 129.25 10.0 4.3 mL 24.6 DMF 40 mL A suspension of N-Fmoc-hydroxylamine 2-chlorotrityl resin (3.188 g, 2.45 mmol, 0. 77 'mmol/g, Novabiochem) in DCM (40 mL) was shaken for 2 h and drained. The resin was treated with 20% piperidine in DMF (40 mL) for 1 hour, washed with DMF (2 x 40 mL), treated a second time with 20% piperidine in DMF (40 mL), washed with DMF (3 x 40 mL) and DCM (3 x 40 mL) and drained completely. In a separate flask, Fmoc-Thr (tBu) -OH (2.927 g, 7.36 mmol), HATU (2.798 g, 7.36 mmol) and DIEA (4.3 mL, 24.6 mmol) were dissolved in DMF (40 mL), stirred three minutes and added to the resin. After shaking for 24 h, the mixture was drained, washed with DMF (4 x 40 mL) and DCM (4 x 40 mL) and dried in vacuo to give 3.500 g of a yellow resin.

Preparation of 4-buta-1, 3-diynyl-N- (2-tert-butoxy-l-hydroxycarbamoyl-propyl)-benzamide on hydroxylamine 2-chlorotrityl resin (4). i. 20% piperidine/DMF ii. EDCI, HOBT, DIEA 0 H H DCM, DMF, 36 h FmocHN Np' \ N /\ O s H O 2 1-1 4 oh/. 4 H Reagent MW Eq. g/mL mmol Fmoc-threonine/resin (2) 0. 77 mmol/g 1.0 2.030 g 1.56 Butadiynyl benzoic acid (3) 170. 16. 2.3 0.617 g 3.63 EDCI 191.71 2.8 0. 834 g 4.35 HOBt 135.13 2.8 0.588 g 4.35 DIEA 129. 25 3.7 1. 0 mL 5.7 DCM. 15 mL DMF 4 mL The resin 2 (2.030 g, 1.56 mmol, 0.77 mmol/g) was swelled in DCM (20 mL) for 2 h and drained. The resin was treated with 20% piperidine in DMF (20 mL) for 1 hour, washed with DMF (4 x 20 mL) and DCM (4 x 20 mL) and drained completely. In a separate flask, 4-buta-1, 3-diynyl- benzoic acid 3 (0.617 g, 3.63 mmol), EDCI (0.834 g, 4.35 mmol), HOBt (0.588 g, 4.35 mmol) and DIEA (1.0 mL, 5.7 mmol) were dissolved in DCM (15 mL) and DMF (4 mL), stirred 45 min and added to the resin. After shaking for 36 h, the mixture was drained, washed with DMF (4 x 20 mL) and DCM (4 x 20 mL) and dried iii vacuo to give 1.900 g of a pale brown resin.

Synthesis of Diacetylenic Threonine Hydroxamic Acids Example 22: (2S, 3R)-4- [4- (3-aminomethyl-phenyl)-buta-1, 3-diynyl]-N- (2-hydroxy-1- hydroxycarbamoyl-propyl) -benzamide (3).

Reagent MW Eq. g/mL mmol Diacetylene on resin (1) 0. 77 mmol/g 1.0 100 mg 0.077 3-Iodobenzylamine HCI (2) 269.51 4.0 83.0 mg 0.308 PdCI2 (PPh3) 2 701.89 0.2 11. 0 mg 0.016 Cul 190.44 0.5 7.0 mg, 0.037 Et3N 101.19 23 250 liL 1.80 DMF 1.5 mL Resin 1 (obtained from previous synthesis) (100 mg, 0. 077 mmol) was swelled in DCM (2 mL) for 1 h and drained. A solution of 3-iodobenzylamine hydrochloride 2 (83.0 mg, 0.308 mmol) and Et3N (250 uL, 1.80 mmol) in DMF (1.5 mL) was purged with a stream of N2 bubbles for two minutes and added to the resin. After mixing for 5 min, PdCl2 (PPh3) 2 (11. 0 mg, 0. 016 mmol) and CuI (7.0 mg, 0.037 mmol) were added and the mixture shaken for 36 h. The resin was drained, washed with DMF (4 x 2 mL), DCM (4 x 2 mL) and cleaved with 10% TFA/DCM (1.5 mL) for 20 min. The solution was collected and the resin was rinsed with additional 10% TFA/DCM (1.5 mL). The cleavage fractions were combined, treated with neat TFA (3.0 mL), stirred for 1 h at rt and concentrated by rotary evaporation to give a crude brown residue. Purification by RP-HPLC (Cis column, CH3CN gradient 5-65%, 0. 1% TFA, UV analysis 300 nm, 28 min) and lyophilization of the collected fractions afforded 4.3 mg (14%) of (2S, 3R)-4- [4- (3-aminomethyl-phenyl)-buta-l, 3-diynyl]-N- (2-hydroxy-l- hydroxycarbamoyl-propyl)-benzamide as a white solid. LRMS (ES+) m/z 392.0 (C22H2tN304 + H requires 392.15) ; RP-HPLC (300 nm, 28 min run) 10.0 min.

Synthesis of Diacetylenic Benzylamine Analogues Example 23: (IS, 2R)-N-2-hydroxy-1-hydroxycarbamoyl-propyl)-4- [4- (4-morpholin-4-ylmethyl- phenyl)-buta-1, 3-diynyl]-benzamide (4) Preparation of threonine diacetylenic benzaldehyde on resin (3).

Reagent MW Eq. g/mL mmol Diacetylene on resin (1) 0.77 mmol/g 1.0 1. 00 g 0.770 4-Iodobenzaldehyde 232.00 4.0 715 mg 3.081 PdCl2 (PPh3) 2 701. 89 0.07 40.0 mg 0.057 Cul 190.44 0.13 19. 0 mg 0.100 Et3N 101.19 9.3 1. 00 mL 7.17 DMF 20.0 mL Resin 1 (1.00 g, 0.77 mmol) was pre-swelled in DCM (25 mL) for 14 h and drained. A solution of 4-iodobenzaldehyde 2 (715 mg, 3.08 mmol) and Et3N (1.00 mL, 7.17 mmol) in DMF (20 mL) was purged with N2 for two minutes and added to the resin. After mixing for 5 min, PdCl2 (PPh3) 2 (40.0 mg, 0.057 mmol) and CuI (19.0 mg, 0.100 mmol) were added and the reaction shaken for 48 h. The resin was drained, washed with DMF (4 x 20 mL), DCM (4 x 20 mL) and dried in vacuo to give 1.100 g of a dark yellow resin.

Preparation of (1S, 2R)-N-2-hydroxy-1-hydroxycarbamoyl-propyl)-4- [4- (4-morpholin-4- ylmethyl-phenyl)-buta-1, 3-diynyl]-benzamide (4).

Reagent MW Eq. mg/µl mmol Benzaldehyde on resin (3) 0. 77 mmol/g 1.0 188 mg 0.141 Morpholine 87.12 6.0 75, uL 0.860 NaCNBH3 62.84 4.5 40 mg 0.637 Trimethyl orthoformate 106.12 6.5 100 4L 0.914 Acetic acid 60.05 12 : 3 100 µL 1. 750 THF 3. 0 mL MeOH 1. 0 mL A solution of morpholine (75 µL, 0.860 mmol) and trimethyl orthoformate (100 juL, 0. 914 mmol) in THF (3.0 mL) was added to a Teflon-lined screw-capped vial containing the resin-bound diacetylenic benzaldehyde 3. The resin was agitated for 10 min, treated successively with acetic acid (100 µL, 1.75 mmol) and a solution of NaCNBH3 (40.0 mg, 0.637 mmol) in MeOH (1.0 mL) and shaken for 44 h. The resin was filtered, washed with DMF (3 x 3 mL) and DCM (3 x 3 mL) and drained. Cleavage from the resin was achieved by treatment with 10% TFA/DCM (2.0 mL) and shaking 20 min. The solution was collected and the resin was rinsed with additional 10% TFA/DCM (2.0 mL). The cleavage fractions were combined, treated with neat TFA (3.0 mL), stirred for 1 h at rt and concentrated by rotary evaporation to give a crude yellow residue. Purification by RP-HPLC (C18 column, CH3CN gradient 5-35%, 0.1% TFA, UV analysis 300 nm, 18 min) and lyophilization of the collected fractions afforded 19.0 mg (29%) of 472 as a fluffy yellow. solid. LRMS (ES+) inlz 462.0 (C26H27N30s + H requires 462.10) ; HPLC (300 nm, 18 min run) 10.3 min.

Synthesis of 4'-Benzamide Diacetylene Threonine Hydroxamic Acid Example 24 : (1S, 2R)-N- (2-hydroxy-1-hydroxycarbamoyl-propyl)-4- {4- [4- (2-amino- ethylcarbamoyl)-phenyl]-buta-1, 3-diynyl3-benzamide (5) Preparation of N- (2-trityl-amino-ethyl)-4-ethynyl-benzamide (3).

Reagent MW Eq. g/mL mmol 4-Ethynylbenzoic acid (1) 146: 14 1.0 0.292 g 2.00 N-Trityl ethylenediamine 302.41 1.3 0.810 g 2.67 EDCI 191.71 1.0 0.382 g 2.00 HOBt 135.13 3.0 0.270 g 2.00 DIEA 129.25 4. 0 1. 40 mL 8.00 DMF. 10.0 mL To a solution of 4-ethynylbenzoic acid 1 (292 mg, 2.00 mmol), EDCI (382 mg, 2.00 mmol), and HOBt (270 mg, 2.00 mmol) in DMF (10 mL) was added N-trityl ethylenediamine 2 (810 mg, 2.67 mmol) and DIEA (1.4 mL, 8.0 mmol). The reaction mixture was stirred 24 h, diluted with EtOAc (200 mL), washed with 0.5 M HCl (60 mL), saturated NaHCO3 (2 x 60 mL), H20 (4 x 60 mL), dried over MgS04 and concentrated to give 836 mg (97% yield) of N-(2-trityl-amino-ethyl)-4-ethynyl-benzamide 3 as a white solid, mp 50-51 °C. Rf = 0.40 (1 : 1 Hexanes/EtOAc).

Preparation of (lS, 2R)-N- (2-hydroxy-1-hydroxycarbamoyl-propyl)-4- {4- [4- (2-amino- ethylcarbamoyl)-phenyl]-buta-1, 3-diynyl}-benzamide (5).

Reagent MW Eq. g/mL mmol Alkyne on resin (4) 0. 77 mmol/g 1.00 150 mg 0.116 4-Ethynylbenzamide (3) 430.54 3.00 151 mg 0.350 PdCl2 (PPh3) 2 701. 89 0.25 21 mg 0.030 Cul 190.44 1.25 28 mg 0.147 Et3N 101.19 9.50 150 1L 1.10 DMF 2.0 mL Resin 4 (150 mg, 0.116 mmol) was swelled in DCM (2 mL) for 1 h and drained. A solution of 4-ethynylbenzamide 3 (151 mg, 0.350 mmol) and Et3N (150 uL, 1.10 mmol) in DMF (2.0 mL) was added and the resin agitated for 5 min. A mixture of PdCl2 (PPh3) 2 (21 mg, 0.030 mmol) and Cul (28 mg, 0.147 mmol) was added and the resin was agitated for 60 h. The resin was drained, washed with DMF (3 x 2 mL), DCM (3 x 2 mL) and cleaved with 10% TFA/DCM (1.5 mL) for 20 min. The solution was collected and the resin was rinsed with additional 10% TFA/DCM (1.0 mL). The cleavage fractions were combined, treated with neat TFA (2.0 mL), stirred for 1 h at rt and concentrated by rotary evaporation to give a crude brown residue. Purification by RP-HPLC (Cl8 column, CH3CN gradient 5-65%, 0.1% TFA, UV analysis 300 nm, 26 min) and lyophilization of the collected fractions afforded 2.0 mg (4% yield) of (lS, 2R)-N-(2-hydroxy-1-hydroxycarbamoyl-propyl), 4-f 4- [4- (2-amino-ethylcarbamoyl)-phenyl]-buta-1, 3-diynyl}-benzamide. LRMS (ES+) m/z 449.1 (C24H24N405 + H requires 449.18) ; RP-HPLC (300 nm, 26 min run) 17.0 min.

Synthesis of 3'-Pyridine Diacetylene Threonine Hydroxamic Acid Example 25: N-((2R)-hydroxy-(lS)-hydroxycarbamoyl-propyl)-4-(4-pyridin-3 -yl-buta-1, 3- diynyl) -benzamide (3) Preparation of N-((2R)-hydroxy-(lS)-hydroxycarbamoyl-propyl)-4-(4-pyridin-3 -yl-buta-1, 3- diynyl)-benzamide (3).

Reagent MW Eq. glmL mmol Alkyne on resin (1) 0. 77 mmol/g 1.0 142 mg 0.109 3-Ethynylpyridine (2) 103.12 3. 4 38 mg 0.368 PdCl2 (PPh3)2 701.89 0. 3 22 mg 0.031 Cul 190.44 1.2 25 mg 0. 131 Et3N 101.19 13 200 jus 1.40 DMF 2. 0 mL Resin 1 (142 mg, 0.109 mmol) was swelled in DCM (2 mL) for 1 h and drained. A solution of 3-ethynylpyridine 2 (38 mg, 0.368 mmol) and Et3N (200 µL, 1. 4 mmol) in DMF (2 mL) was added and the resin agitated for 5 min. A mixture of PdCl2(PPh3)2 (22 mg, 0.031 mmol) and Cul (25 mg, 0.131 mmol) was added and the resin was agitated for 72 h. The resin was drained, washed with DMF (3 x 2 mL), DCM (3 x 2 mL) and cleaved with 10% TFA/DCM (1.5 mL) for 20 min. The solution was collected and the resin was rinsed with additional 10% TFA/DCM (1.0 mL). The cleavage fractions were combined, treated with neat TFA (2.0 rnL), stirred for 1 h at rt and concentrated by rotary evaporation to give a crude brown residue. Purification by RP-HPLC (Cl8 column, CH3CN gradient 5- 65%, 0.1% TFA, UV analysis 300 nm, 24 min) and lyophilization of the collected fractions afforded 4.4 mg (11% yield) of N-((2R)-hydroxy-(1S)-hydroxycarbamoyl-propyl)-4-(4-pyridin-3 -yl-buta-1, 3- diynyl)-benzamide. LRMS (ES+) m/z 364.0 (C2oHl7N304 + H requires 364. 13) ; RP-HPLC (300 nm, 24 min run) 11. 2 min.

Example 26: Synthesis ofN- (l- (N-hydroxycarbamoyl) (lS, 2R)-2-hydroxy propyl) {4- [4- (6- morpholin-4-yl (3-pyridyl) ) buta-1, 3-diynyl] phenyl} carboxamide (5) 0 Br 2 H Thr-NH-0-Trt- [Rink], DIC, HOBT, DIEA, DMF 1. Pd2dba3, I. Pdzdbaa, PdC12 (PPh3) 2, Et3N, DMF 3 2. NaOH, MeOH OH OtBu H zozo O 1. Morpholine, NMP HO'N N 90 c 0 H 0 H 2. TFA, water ZON 4 N N ci (DO Cl Reagent MW EQ g/ml mmol Dibromovinylbenzoic acid (1) 320 1.0 9.6 g 30.0 2-Chloro-5-ethynyl-pyridine 138 1.3 5. 43 g 39.0 Pd2dba3 915 0.01 274 mg 0.3 (1% cat. ) TMPP 352 0.04 422 mg 1.2 (4%) TEA 101 3.0 12. 5 ml 90.0 DMF 90 ml degassed with argon Preparation. of 4-[4-(6-Chloro-pyridin-3-yl)-buta-1,3-diynyl]-benzoic acid methyl ester.

4- [4- (6-Chloro-pyridin-3-yl)-buta-1, 3-diynyl]-benzoic acid was made according to the method of Wang Shen and Sheela A. Thomas in Org. Lett. 2000,2 (18), 2857-2860.

A solution of 4- (2, 2-dibromo-vinyl) -benzoic acid methyl ester (1) (9.6g, 30. Ommol), ethynyl- pyridine (2) (5.43g, 39. Ommol), Pd2dba3 (274mg, 0. 3mmol), tris (4-methoxyphenyl) phosphine (TMPP) (422mg, 1. 2mmol) were dissolved in argon sparged (5 min. ) DMF (60ml). The reaction was sparged with argon for 1 min. TEA (12. 5ml, 90. 0mmol) was added to the stirred reaction mixture that was then heated under argon at 85 °C for 3 hours. The reaction was found complete by LCMS. The reaction was cooled to rt and diluted with EtOAc/hexane (1 : 1) (500ml). The organic phase was washed with 1M NaOH (2x80ml), water (2x80m1), sat. brine (80ml), dried with Na2S04, filtered and concentrated under reduced pressure to give crude product. The residue was filtered through a filter plug of silica eluting with EtOAc/hexane (1 : 1). The fractions with product were evaporated to give 9.06 g of product in good purity (-96% pure). The material was taken on without further purification.

Preparation of 4- [4- (6-Chloro-pyridin-3-yl)-buta-1, 3-diynyll-benzoic acid (3) A 6M aq. solution of NaOH (15ml) was added to a stirred solution of 4- [4- (6-Chloro-pyridin-3- yl)-buta-1, 3-diynyl] -benzoic acid methyl ester. (9.06g, 30mmol) in MeOH (350ml) at rt. The reaction solution was heated to reflux for 3 hours. The reaction stayed a mixture and did not turn clear. HPLC and LCMS indicated that the reaction was forming side products. The reaction was cooled to rt and some MeOH (-200ml) was removed by evaporation under reduced pressure. Water (400ml) was added to the mixture. Conc. HC1 was added dropwise to the stirred solution until acidic by pH paper (pH2). The yellow precipitate that formed was collected by suction filtration. The solid was washed with water (3x20ml) and hexane (2x20ml) to give the crude product. HPLC indicated that there was approximately 40% product in the mixture. The crude reaction product was purified by flash chromatography using EtOAc (8-10%) /hexane as eluant. The pure fractions were evaporated and dried in vacuo to give 4.2 g of product 3 in 50% yield.

Preparation of [4- [4- (6-chloro-pyridin-3-yl)-buta-1, 3-diynyl]-benzoyl]-HN-Thr (OtBu) - hydroxamic acid trityl resin (4) 4- [4- (6-Chloro-pyridin-3-yl)-buta-1, 3-diynyl] -benzoic acid (3) was coupled to a tert-butyl protected threonine pre-loaded on hydroxylamine 2-chlorotrityl resin following the same procedure as used for Example 26. The coupling employed DIC and HOBT. [N-Fmoc-hydroxylamine 2- chlorotrityl resin was purchased from Novabiochem cat. # 01-64-0165.] Preparation of N- (2-Hydroxy-l-hydroxycarbamoyl-propyl)-4- [4- (6-morpholin-4-yl-pyridin-3- yl)-buta-1, 3-diynyl]-benzamide (5) OH OtBu H W 0 H > ° 1. Morpholine, NMP HO' NJA /O N-IN 90 c 3-0 0 H I 0 H 1 2. TFA, water N \N I/N 4 /5 O cl A solution of morpholine (300uL) in NMP (lml) was added to a vial containing the 2- cloropyridine resin (4) (150mg, 0.12mmol). The reaction mixture was purged with argon and heated to 85-90 °C for 24 hours. The resin was drained and washed with DMF and DCM alternately several times. The product was cleaved from the resin through treatment with a TFA/water solution (80: 20) (1. 5ml) for 45 min. The resin was filtered and washed with fresh TFA/water solution (80: 20) (0. 5ml).

The combined TFA and organic fractions were diluted with CH3CN/water (1: 1) (lOml), water (2ml) and lyophilized. The crude product was purified by prep. HPLC. The crude product was dissolved in DMSO (lml), passed through a Teflon syringe filter, and the clear filtrate was injected on a preparative HPLC. The purification used a 20x50 mm Ultro 120 C18 column running a 22 ml/min 2% gradient (AcCN/water, 0.1% TFA) for 16 min. The purified fractions were lyophilized to dryness to give 2.2 mg of pure product as the TFA salt (-32% yield).

Example 27: Synthesis of 4- [4- (4-Amino-phenyl)-buta-1, 3-diynyl]-N- (2-hydroxy-1- hydroxycarbamoyl-propyl)-benzamide (4) 0 OtBu vOH H >. tJ DIC, HOBT, N DIEA, DMF 0 NH2 2 1 Jt J 2 H2N OH OtBu H 0 O TFA, water HO / o'N N H oh 3 4 NH2 nu2 NH Preparation of 2-4- [4- (4-Amino-phenyl)-buta-1, 3-diynyl]-benzoylamino}-3-tert-butoxycarbonyloxy- butyric hydroxamic acid trityl resin (3).

Reagent MW EQ g/ml mmol H-Thr (Boc)-NHO-Trt Resin (1) 1.0 5.8 g 4.47 1,3-diynyl benzoic acid (2) 261.3 1.4 1. 64 g 6.25 HOBT 135. 1 1.4 0.85 g 6.25 DIC 126.2 1.4 0. 98 ml 6.25 DIEA 129.25 3.5 2. 7 ml 15.6 DMF 50 ml DIEA (2. 7ml, 15. 6mmol) was added to a stirred solution of 4- [4- (4-Amino-phenyl)-buta-1, 3- diynyl]-benzoic acid (2) (1.64g, 6. 3mmol), HOBT (0.85g, 6. 3mmol), DIC (0. 98ml, 6. 3mmol) in DMF (50ml). After 2 min. , the Thr hydroxylamine resin (5.8g, 4. 5mmol) was added in one portion. [N- Fmoc-hydroxylamine 2-chlorotrityl resin was purchased from Novabiochem cat. # 01-64-0165.] After 12 hours at rt, the reaction was found complete by LCMS. The resin was drained and washed with DMF and DCM alternately 3 times each. The product on resin 3 was used as is in subsequent reactions without further treatment.

Preparation of 4- [4- (4-Amino-phenyl)-buta-1, 3-diynyl]-N- (2-hydroxy-1-hydroxy carbamoyl- propyl)-benzamide (4) Reagent MW EQ g/ml mmol 1,3-diynyl benzoic Thr Resin (3) 1.0 120 mg 0.09 TFA/water (80: 20) 1.5 ml The product (4) (120mg, 0. 09mmol) was cleaved from the resin through treatment with a TFA/water solution (80: 20) (1. 5ml) for 45 min. The resin was filtered and washed with fresh TFA/water solution (80: 20) (0. 5ml). The combined TFA and organic fractions were diluted with CH3CN/water (1: 1) (lOml), water (2ml) and lyophilized. The crude product was purified by prep.

HPLC. The crude product was dissolved in DMSO (lml), passed through a Teflon syringe filter, and the clear filtrate was injected on a preparative HPLC. The purification used a 20x50 mm Ultro 120 C18 column running a 22 mUmin 2% gradient (AcCN/water, 0. 1% TFA) for 16 min. The purified fractions were lyophilized to dryness to give 2.2 mg of pure product as the TFA salt. The product (4) was lyophilized again from CH3CN/water with 10 equivalents of HCl to remove most of the TFA to yield 2 mg of product as the HCl salt (-53% yeild).

Example 28: Synthesis of 4-f 4- [4- (2-Dimethylamino-acetylamino)-phenyl]-buta-1, 3-diynyl}-N- (2- hydroxy-l-hydroxycarbamoyl-propyl)-benzamide (6) (Continued from compound 3 of Example 27 above) 0 tBu OtBu OtBu O Ci _. N. . N'4 O I N/ ol N Lutidine, Dcm 0 H 0 H 5 Br zon NH- H '-NH2 H OH H 0 HO'N 1. Me2NH, NMP O H WJIX 2. TFA, water 6 \Nt H H Preparation of 2- (4- {4- [4- (2-Bromo-acetylamino)-phenyl]-buta-1, 3-diynyl}-benzoylamino)-3-tert- butoxycarbonyloxy-butyric acid hydroxamate trityl resin (5). 0 OtBu OtBu Br H o H cri N ou H 'M'u. \ \ zozo W 5 s Br 5 N)-,/Br NH2 H "NH2" Reagent MW EQ g/ml mmol Amino 1,3-diynyl benzoic Thr Trt Resin (3) 1.0 0.75 g 0.578 Bromo-acetyl chloride 157.4 8.0 0.728 g 4.62 Lutidine 107 10.0 1. 07 ml 9.24 DMF 6 ml A solution of bromo-acetyl chloride (0.75g, 0.58mmol) in DCM (2ml) was added to a mixture of 2-f 4- [4- (4-Amino-phenyl)-buta-l, 3-diynyl]-benzoylamino}-3-tert-butoxycarbonyloxy-butyric acid hydroxamate Trt Resin (3) (0.75g, 0. 58mmol), lutidine (l. lml, 9.2mmol) and DCM (4ml) at rt with shaking. After shaking for 1.5 hours, the reaction was found complete by LCMS. The resin was drained and washed with DCM (2xlOml), DMF (3xlOml) and DCM (3xlOml) again. The resin was drained and dried in vacuo. The product on resin 5 was used as is in subsequent reactions without further treatment.

Preparation of 4-{4-[4-(2-Dimethylamino-acetylamino)-phenyl]-buta-1,3-diyny l}-N-(2-hydroxy- l-hydroxycarbamoyl-propyl)-benzamide (6). OtBu OH H 0 1. Me2NH, NMP H *T0 N, O p H (. 2. TFA, water HO/N H O H 1. 2. TFA, I' I 1-11 H H N H H Reagent MW EQ g/ml mmol Bromo acetic Thr Trt Resin (5) 1.0 125 mg 0.093 Dimethyl amine 45.08 0. 2 ml excess NMP 1. 2 ml A solution of dimethyl amine (0. 2ml) in NMP (1. 2ml) was added to bromo acetic Thr Trt Resin (5) (125 mg, 0. 09mmol) at rt with shaking. After shaking for 12 hours, the reaction was found complete by LCMS. The resin was drained and washed with DCM (2xlOml), DMF (3xlOml) and DCM (3xlOml) again. The product (6) was cleaved from the resin through treatment with a TFA/water solution (80: 20) (1. 5ml) for 45 min. The resin was filtered and washed with fresh TFA/water solution (80: 20) (0. 5ml). The combined TFA and organic fractions were diluted with CH3CN/water (1: 1) (10ml), water (2ml) and lyophilized. The crude product was purified by prep.

HPLC. The crude product was dissolved in DMSO (lml), passed through a Teflon syringe filter, and the clear filtrate was injected on a preparative HPLC. The purification used a 20x50 mm Ultro 120 C18 column running a 22 ml/min 2% gradient (AcCN/water, 0.1% TFA)'for 16 min. The purified fractions were lyophilized to dryness to give 2 mg of pure product as the TFA salt (~37% yeild).

Example 29: Synthesis of 4- {4- [4- (2-Amino-4-methyl-pentanoylamino)-phenyl]-buta-1, 3-diynyl}- N-(2-hydroxy-1-hydroxycarbamoyl-propyl)-benzamide (7) (Continued from compound 3 of Example 27 above) OH H 0 OtBu 1. FmooL-Leu, HATU, HO) N) + H 0 DIEA, DMF 0 H N 2. Piperldine, 0 H 3. TFA, water 0 NH2 N \ 3 \ 7 H \+NH2) Reagent MW EQ g/ml mmol Amino 1,3-diynyl benzoic Thr Trt Resin (3) 1.0 125 mg 0. 093 Fmoc-L-leucine 353.42 4.0 0.135 g 0.384 HATU 380 4.0 0. 146g 0.384 DIEA 129.25 8.0 133 ul 0.768 DMF 1. 5 ml A solution of Fmoc-L-leucine (0.135g, 0. 38mmol), HATU (0.146g, 0. 38mmol) in DMF (1. 5ml) was made. After 2 min. of shaking, the activated acid was added to the amino 1,3-diynyl benzoic Thr Trt Resin (3) (125 mg, 0. 09mmol) at rt with shaking. After shaking for 36 hours, the reaction was drained and washed with DCM (2x4ml), DMF (3x4ml) and DCM (3x4ml) again. The resin was treated with 20% piperizine in DMF (4ml) for 2 hours twice. The resin was drained and washed with DMF and DCM alternately several times. The product was cleaved from the resin through treatment with a TFA/water solution (80: 20) (1. 5ml) for 45 min. The resin was filtered and washed with fresh TFA/water solution (80: 20) (0. 5ml). The combined TFA and organic fractions were diluted with CH3CN/water (1: 1) (lOml), water (2ml) and lyophilized. The crude product was purified by prep. HPLC. The crude product was dissolved in DMSO (lml), passed through a Teflon syringe filter, and the clear filtrate was injected on a preparative HPLC. The purification used a 20x50 mm Ultro 120 C18 column running a 22 mUmin 2% gradient (AcCN/water, 0. 1% TFA) for 16 min. The purified fractions were lyophilized to dryness to give 1.7 mg of pure product (7) as the TFA salt (-30% yield).

Examples 30-1307 of Table 1 were synthesized according to the synthetic schemes described above.

Biological protocols and data P. aeruginosa LpxC Inhibition Assay The assay followed the general method of Hyland et al (Journal of Bacteriology 1997 179, 2029-2037: Cloning, expression and purification of UDP-3-O-acyl-GlcNAc deacetylase from Pseudomonas aeruginosa : a metalloamidase of the lipid A biosynthesis pathway) and the radiolabeling procedure is according to Kline et al. supra. Briefly, samples were incubated with 2 nM P. aeruginosa LpxC and 150 nM [3H-Ac]-UDP-3-0-(R-3-hydroxydecanoyl)-GlcNAc in a total volume of 50 uL for 90 min at room temperature. Reactions were carried out in 96-well polypropylene plates in 50 mM sodium phosphate buffer, pH 7.5, containing 1 mg/mL BSA. Reactions were stopped by the addition of 180 uL of a 3% suspension of activated charcoal powder in 100 mM sodium acetate, pH 7.5.

Supernatants were clarified by centrifugation. A portion of the clarified supernatant, containing the enzymatically released [3H] -acetate, was transferred to opaque white 96-well plates containing scintillation fluid. The radioactivity was measured in a Perkin-Elmer/Wallac Trilux Microbeta counter.

Control reactions to which 5 mM EDTA had been added were included with each run to determine nonspecific tritium release.

Bacterial Screens and Cultures Bacterial isolates were cultivated from-70°C frozen stocks by two consecutive overnight passages at 35°C in ambient air on 5% blood agar (Remel, Lenexa, KS). Clinical isolates tested were from a collection composed of isolates collected during clinical trials and recent clinical isolates obtained from various geographically diverse hospitals in the US. Quality control and primary panel strains were from the American Type Culture Collection (ATCC; Rockville, MD), with the exception of P. aeruginosa PA0200, a strain with a deletion of the mexABoprM genes that was received from Dr. H. Schweizer. This strain does not express the principal multidrug efflux pump and is hypersusceptible to many antibacterials. Strain Z61 (ATCC 35151) is also hypersusceptible to antibacterials. It is thought that the hypersusceptibility of this strain is the result of increased permeability of its outer membrane (Angus BL et al, Antimicrobial Agents and Chemotherapy 1982 21,299-309 : Outer membrane permeability in Pseudomonas aeruginosa : Comparison of a wild-type with an antibacterial-supersusceptible mutant).

Susceptibility Testing Minimum Inhibitory Concentrations (MICs) were determined by the broth microdilution method in accordance with the National Committee for Clinical Laboratory Standards (NCCLS) guidelines. In brief, organism suspensions were are adjusted to a 0.5 McFarland standard to yield a final inoculum between 3x105 and 7x105 colony-forming units (CFU)/mL. Drug dilutions and inocula were made in sterile, cation adjusted Mueller-Hinton Broth (Remel). An inoculum volume of 100 was added to wells containing 100 1 of broth with 2-fold serial dilutions of drug. All inoculated microdilution trays were incubated in ambient air at 35° C for 18-24 hours. Following incubation, the lowest concentration of the drug that prevented visible growth was recorded as the MIC. Performance of the assay was monitored by the use of laboratory quality-control strains against tobramycin, that has a defined MIC spectrum, in accordance with NCCLS guidelines.

Efficacy in mouse model of systemic Pseudomonas aeruginosa infection Female Balb/c mice were injected intraperitoneally with 0.5 ml of a bacterial suspension containing approximately 100 times the dose that would kill 50% of animals (LDso) of P. aeruginosa strain PAO1 or E. coli ATCC 25922. At one and five hours post infection, the test compound was injected intravenously in doses ranging from 5 mg/kg to 100 mg/kg, five mice per group. Mice were observed for 5 days, and the dose of compound resulting in survival of 50% of mice (EDso) was calculated.

Drug Combination (Synergy) Studies I. Principle Checkerboard experiments can be performed to assess potential interactions between primary drug of interest (&num 1) and other related antibacterials (#2). P. aerugi71osa ATCC 27853, S. aureus ATCC 29213 and other organisms can be used as challenge strains as well as selected clinical isolates. Broth microdilution format can be used to assess the activity of drug #1 and test compound alone and in combination. Two-fold dilutions of the two compounds to be tested (each bracketing the expected MIC value) are used. The fractional inhibitory concentration (FIC) was calculated as the MIC of compound #1 in combination with a second compound, divided by the MIC of compound #1 alone. A summation FIC (EFIC) was computed for each drug combination as the sum of the individual FICs of compound #1 and #2. Synergy was defined as an zFIC zu 0.5, indifference as an EFIC between 0.5 and 4, and antagonism as EPIC > 4. The lowest EFIC was used for the final interpretation of drug combination studies., Interpretation of summation (EFIC) a) Synergism, x #0. 5 b) Indifference, 0.5 < x 4 c) Antagonism, x > 4 Table 2: Demonstration of Antibacterial activity of Select Compounds from Table 1 Enzyme inhibitory activity Compound ICgo (nM) Example # 12 < 100 nM 572 < 100 nM 481 < 100 nM 19 < 100 nM 516 < 100 nM 280 < 100 nM 366 < 100 nM 777 < 100 nM 315<100nM 779 < 100 nM 860 < 100 nM 801 < 100 nM 13 < 100 nM Table 3: Antibacterial activity vs standard panel of organisms (MIC, µg/ml).

MIC Key MIC's of 6.25 ug/ml or less = A MIC's of greater than 6.25 ug/ml to 50 ug/ml = B . MIC's of greater than 50 ug/ml = C Bacterial strain: P. aeruginosa E. coli S. aureus hyper-permeable P. aeruginosa 27853 25922 29213 P. aerug. 35151 PA0200 mexAB Compound Example # 12 A A C A A 572 A A C A A 481 A A C A 19 A A B A A 516 A A C A A . 280 A A C A A 366 A A C A A 777 A A C A A 315 A A C A A 779 A A C A A 860 A A C A A 801 A A c A A 13 A A C AA A Table 4: Antibacterial activity vs cystic fibrosis isolates of Pseudomonas aeruginosa (MIC, pLg/ml). Strains have the following phenotypes: 3198 and 3236, sensitive to most antibacterials ; 2196, resistant to ciprofloxacin; 3224, resistant to ceftazidime; 3317, resistant to aztreonam; 1145 and 3206, multi-drug resistant. MIC Key MIC's of 6. 25 ug/ml or less = A MIC's of greater than 6.25 ug/ml to 50 ug/ml = B MIC's of greater than 50 ug/ml = C Strain number: 3198 3236 2196 3224 3232 3317 1145 3206 Phenotype: Sensitive Sensitive Cipro R Tobra R Ceftaz. R Aztr. R MDR MDR LpxC inhibitors 12 A A B A A A A A 481 A A A A A A A A 19 A A A A A A A A 516 A A A A A A A A 280 A A B A A A A A 366 A A A A A A A A 777 A A A A A A A A 315 A A A A A A A A 779 A A A A A A A A 801 A A A A A A A A 13 A A A A A A A A Comparator antibacterials Tobramycin 2 0.5 2 64 1 2 8-32 64 Aztreonam 1 0.5 1 1 1 64 >128 > 128 Ceftazidime 2 0.25 2 2 64 4 >128 > 128 Cefepime 4 2 2 8 2 8 >128 32 Ciprofloxacin 1 0.06 > 8 2 2 0.5 4 >8 Table 5: Antibacterial activity vs non-CF clinical isolates of P. aeruginosa and vs other gram- negative pathogens. Set 1: non-fermenting organisms. P. aer. , P. aeruginosa; Acinet. calc., Acinetobacter calcoaceticus; Alcal. xyl. , Alcaligenes xylosoxidans; B. cep. , Burkholderia cepacia; S. malt. , Stenotrophomonas maltophilia MIC Key MIC's of 6.25 ug/ml or less = A MIC's of greater than 6.25 ug/ml to 50 ug/ml = B MIC's of greater than 50 ug/ml = C Species: P. aer 27853 P. aer. PAO1 P. aer 12307 P. aer psa-6b Acinet. calc. Alcal. xyl B. cepacia S. malt. LpxC inhibitors 12 A A A A A A B A 481 A A A A C C B C 19 A A A A A B B B 516 A A A C C C C 280 A A A A C B B B 366 A A A B C A B B 777 A A B A B A C 315 A A A A C B A A 779 A A A C A A B 801 A A A B C B C 13 A A A C A A B Comparator antibacterials Tobramycin 8 2 2 64 64/>128 0.5 Aztreonam 16 32 32 32 64 > 128/16 Ceftazidime 4 64 16 1 8/4 1 Cefepime 2 8 8 8 32/16 8/1 Meropenem 0.5 0.25 4 0.5 4 64 Pip/Tazo 4 >128 8 1 64 16 Ciprofloxacin 0.5 2 0.5 0.5 Table 6: Antibacterial activity vs non-CF clinical isolates of P. aeruginosa and vs other gram- negative pathogens, continued. Set 2: enteric organisms. E. aer. , Enterobacter aerogenes; E. clo., Enterobacter cloacae; E. coli, Escherichia coli ; K. pneu., Klebsiella pneumoniae; K. oxy., Klebsiella oxytoca; P. mir. , Proteus mirabilis ; S. marc. , Serratia marcescens.

MIC Key MIC's of 6.25 ug/ml or less = A MIC's of greater than 6.25 ug/ml to 50 ug/ml = B MIC's of greater than 50 ug/ml = C Species: E. aer. E. clo. E. coli 1619 E. coli 2788 K. pneu. K. oxy. P. mir. S. marc. LpxC inhibitors 12 C A A A A A A A 481 C A A A A A A A 19 A A A A A A A A 516 C B A B C C C A 280 C A A A B C B B 366 C A A A B B A A 777 B A A A A A A A 315 C A A A C C C B 779 C A A A B B B A 801 B A A A A A A A 13 C A A A A A A A Comparator antibacterials Tobramycin 64 0.06 16/64 0.06/2 64 1 2 2 Aztreonam <=0.13 128/64 <=0.13/0.25 2 0.5 <=0.13 <=0.13 Ceftazidime 32 0.25 > 128 0.25/<=0.13 8 0.25 <=0.13 0.25 Cefepime <=0.13 4/<=0.13 <=0.13 8 <=0.13 <=0.13 <=0.13 Meropenem 2 <=0.06 0.25/0.13 <=0.06 0.13 <=0.06 0.5 0.13 Pip/Tazo 2 > 128 1 > 128 2 0.25 1 Ciprofloxacin > 8 0.015 2 0.03 0.06 0.03 0.03 0.25 Table 7: Drug Combination (Synergy) Studies Result Minimum Concentration (mg/ml) required to inhibit grouth of E. coli 25922 Eiythromycin LpxC inhibitor 925 LpxC inhibitor 925 only-6. 25 Erythromycin only 128 LpxC inhibitor 925 2 0. 78 +erythromycin Each of the Example compounds of Table 1 was synthesized and assayed as described above.

Many of the Example compounds 1-1307 displayed an ICso value of less than 10 uM with respect to LpxC. Many of these compounds displayed an IC50 value of less than or equal to 1 I or less than or equal to 0.1 N, M. Many of these compounds exhibited ICso values of less than or equal to 0. 050 uM, less than or equal to 0. 030 µM, less than or equal to 0. 025, uM, or less than or equal to 0. 010 uM.

It should be understood that the organic compounds according to the invention may exhibit the phenomenon of tautomerism. As the chemical structures within this specification can only represent one of the possible tautomeric forms, it should be understood that the invention encompasses any tautomeric form of the drawn structure. TABLE 1 Example Structure Name MH+ 83C'OH Chiral H N N-OH 3, 4-difluoro-N- { (1S, 2R)-2-hydroxy-1- FX [(hydroxyamino) carbonyl] propyl} benzamide F 30 F 13CY OH Chiral QYH-oH (2S 3R)-N, 3-dihydroxy-2- [ (4- H o phenylbutanoyl) amino] butanamide 31 ac °H c'im (2S, 3R)-N, 3-dihydroxy-2- ( {4- [4- H, ; M-OH (methyloxy) phenyl] butanoyl} amino) butanami 311. 3 de 32 õi3C OH Chiral 11 ch. ra. N- { (lS, 2R)-2-hydroxy-l- N-OH [ (hydroxyamino) carbonyl] propyl}-5- 295. 3 phenylpentanamide 33 oi3C OH Chìr31 ii Y H (2E, 4E)-N-{(lS, 2R)-2-hydroxy-1- 'N °H [ (hydroxyamino) carbonyl] propyl}-5- 291. 3 phenylpenta-2, 4-dienamide 34 H Jt N@N-oH (2E)-N- { (lS, 2R)-2-hydroxy-l- | H o [(hydroxyamino) carbonyl] propyl}-3- 265. 3 phenylprop-2-enamide 35 35 COH Chiral 63 OH (2S, 3R)-3-hydroxy-2- ( { (2E)-3- [4- o (methyloxy) phenyl] prop-2- 280. 3 enoyl} amino) butanoic acid 36 36 NN NH-OH (3R)-3-amino-N-{(1S, 2R)-2-hydroxy-1- N °H [ (hydroxyamino) carbonyl] propyl}-5- 310. 4 37 phenylpentanamide 37 Example Structure Name MH+ õi3Ce, OH Chiral A 1 H (2E)-3- (4-iluorophenyl)-N- { (lS, 2R)-2- hydroxy-1-283. 3 < [(hydroxyamino) carbonyl] propyl} prop-2- 38 enamide 38 C OH Chiral Jk N) N-OH (2E)-3-(3-bromophenyl)-N- {(1 S, 2R)-2- I H o hydroxy-1_ [ (hydroxyamino) carbonyl] propyl} prop-2- enamide 39 Br ffic OH Chiral TH-oH N- { (lS, 2R)-2-hydroxy-l- 1- 0 1 (hydroxyamino) carbonyl] propyl)-4-f [ (2- 372. 4 phenylethyl) amino] methyl} benzamide 40 , c o"cn, m >) HN-OH N-{(lS, 2R)-2-hydroxy-1- 'H' ; [ (hydroxyamino) carbonyl] propyl}-4- { [ (4- 400. 5 phenylbutyl) amino] methyl} benzamide 41 NC OH r-oH 4- [ (cyclopropylamino) methyl]-N- { (1S, 2R)-2- hydroxy-1-308. 3 17" [(hydroxyamino) carbonyl] propyl} benzamide [ (Y Y) Y] p PY} 42 o"cm 4- [ (hexylamino) methyl]-N- { (1S, 2R)-2- 6c N ; hydroxy-l-352. 4 [(hydroxyamino) carbonyl] propyl} benzamide 43 ffic OH Chiral x-b-o"N- { (1S, 2R)-2-hydroxy-1- N=g NJSi HN O [(hydroxyamino) carbonyl] propyl}-4- { [ (2- 373. 4 pyridin-2-ylethyl) arnino] methyl} benzamide 44 C OH Chiral N- { (IS, 2R)-2-hydroxy-l- J ; H [(hydroxyamino) carbonyl] propyl}-4- (4- 337. 4 N H, Nv methylpiperazin-l-yl) benzamide HC" 45 61 C OH Chiral N-f (I S, 2R)-2-hydroxy-l- N) ; 0-0 H [ (hydroxyamino) carbonyl] propyl}-4- (piperidin 336. 4 ON,-,-0 1-yhnethyl) benzamide 46 Exa le Structure Name MH+ mp _ N OH cnim N_ { (1S, 2R)-2-hydroxy-1- ° ; ! M-OH [ (hydroxyaniino) caxbonyl] propyl)-4-338. 4 N O (morpholin-4-ylmethyl) benzamide 47 0 C OH Chilal N-{(lS, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl}-4- ( { [3- (2- kMJLJ"o oxopyrrolidm-l- yl) propyl] amino} methyl) benzamide 48 C'OH Chiral N- { (lS, 2R)-2-hydroxy-1- llllllll a'°" [ (hydroxyamino) carbonyl] propyl}-4- { [ (3- 386. 5 49 phenylpropyl) amino] methyl} benzamide 49 C OH Chiral N'oH (2S, 5R)-N- { (1 S, 2R)-2-hydroxy-l- sH H O [(hydroxyamino) carbonyl] propyl}-5- 308. 3 phenylpyrrolidine-2-carboxamide 50 50 C OH Chiral N' ;'N-OH (2R, 5 S)-N- { ( 1 S, 2R)-2-hydroxy-1- $ON oI [ (hydroxyamino) carbonyl] propyl}-5- 308. 3 phenylpyrrolidine-2-carboxamide 51 N3C OH Chiral (2S, 3R)-2-1 [ (3S)-3-amino-4- N N-O H phenylbutanoyl] amino}-N, 3-296. 3 o dihydroxybutanamide 52 C OH Chiral (2S, 3R)-2-{[(2S)-2-amino-4- WNXt phenylbutanoyl] amino}-N, 3-296. 3 NHZ H o dihydroxybutanamide 53 C OH Chiral . AJM-oH N- { (lS, 2R)-2-hydroxy-l- N<NJ H O [(hydroxyamino) carbonyl] propyl}-6- (2- 337. 4 G pyrrolidin-l-ylethyl) pyridine-3-carboxamide 54 oH3C+HeH N OH 2- { [ (4'-ethyl-l, l'-biphenyl-4- yl) carbonyl] amino}-3-hydroxy-3- 342. 4 "methylbutanoic acid H3C I i 55 Example Structure Name MH+ CH, H3C OH 0 N OH 2-1 [4- (4-ethylphenyl) phenyl] carbonylamino}-356 4 H ° 3-hydroxy-4-methylpentanoic acid 56 HC,, a 56 s H [ (4'-ethyl- 1, l'-biphenyl-4- H3 YI) Carbonyllaniino) (thien-2-yl) acetic acid 57 H sp N-(2- {[(1, 1-dimethylethyl) oxy] arnino}-2-oxo- N " cH 1-thien-2-ylethyl)-4'-ethyl-1, 1'-biphenyl-4- 437. 6 H3C XCH a carboxamide Cl, 58 , QH3 HXN CH 3-(dimethylamino)-2-{[(4'-ethyl-1, l'-biphenyl-341 4 OH 4-yl) carbonyl] amino} propanoic acid 3 59 on °" 4'-ethyl-N- { (lS)-l- [ ( { (lS, 2R)-2-hydroxy-l- r-¢CN92 oH [(hydroxyamino) carbonyl] propyl} amino) carbo 456. 6 , c. rl-\r-o 00 nyl]-3-methylbutyl)-1, 1'-biphenyl-4- carboxamide 60 Chilal 4'-ethyl-N-[(1 S)-2-({(1 S, 2R)-2-hydroxy-1- H3C OH ° -_oH [ (hydroxyamino) carbonyl] propyl} amino)-2-490 6 oxo-1- (phenyhnethyl) ethyl]-l, l'-biphenyl-4- carboxamide 61 o ch, (2S)-l- [ (4'-ethyl-l, l'-biphenyl-4-yl) carbonyl]- H H3C N-I (IS, 2R)-2-hydroxy-l- Ho 440. 5 ' pb. OH [ (hydroxyamino) carbonyl] propyl} pyrrolidine- 2-carboxamide 62 Chimi °n''°'4'-ethyl-N- [ (1S)-2- ( { (1S, 2R)-2-hydroxy-1- "Y jj [ (hydroxyamino) carbonyl] propyl} ammo)-l-.-- 0 0 (lH-imidazol-4-yhnethyl)-2-oxoethyl]-1, 1 H, C O biphenyl-4-carboxamide 63 (3S)-2- [ (4'-ethyl-1, 1'-biphenyl-4-yl) carbonyl]- HsC rC OH N- { (1S, 2R)-2-hydroxy-l- M. [ (hYdroxyamino) carbonyllpropyll-1, 2, 3, 4- 0 0"tetrahydroisoquinoline-3-carboxamide 64 Example Structure Name MH+ C (2S)-2- [ (I, I--biphenyl-4-ylacetyl) amino]-N- < mf N OH { (lS, 2R)-2-hydroxy-l- ho [ (hydroxyamino) carbonyl] propyl}-4- methylpentanamide 65 choral n Q H3C OH (2S, 3R)-2- ( { (2S)-2- [ (1, 1'-biphenyl-4- -OH ylacetylyalnino]-3-phenylpropanoyl} amino)-476. 5 o N, 3-dihydroxybutanamide 66 "o °"''' (2S, 3R)-2- { [ (2S)-2- [ (1, 1'-biphenyl-4- v/H, c o"ylacetyl) amino]-3- (4- wino ; hydroxyphenyl) propanoyl] amino}-N, 3- ° dihydroxybutanamide 67 < chn31 (2S)-l-(l, l'-biphenyl-4-ylacetyl)-N- {(1 S, 2R)- HC 2-hydroxy-l-426. 5 b, [ (hydroxyamino) carbonyl] propyl} pyrrolidine- oH 2-carboxamide 68 N Chiml (2S, 3R)-2-{[(2S)-2-[(1nl-biphenyl-4- 0-OH ylacetyl) amino]-3- (lH-imidazol-4- 466. 5 M : ; H yl) propanoyl] amino}-N, 3- 69 dihydroxybutanamide 69 N 0-Chiral (2S)-2- [ (1, 1'-biphenyl-4-ylacetyl) amino]- . I N-1- { (lS, 2R)-2-hydroxy-l- I O [(hydroxyamino) carbonyl] propyl} pentanediam [ (Y Y) Y] p pY} p 0 ide 70 H ai) (3S)-3- [ (l, l'-biphenyl-4-ylacetyl) amino]-4- HO Ha° OH ( { (lS, 2R)-2-hydroxy-l- 444. 5 tu [ (hydroxyamino) carbonyl] propyl} amino)-4- oxobutanoic acid 71 (2S, 4R)-1-[(4'-ethyl-1, 1'-biphenyl-4- yl) carbonyl]-4-hydroxy-N- { (lS, 2R)-2-hydroxy OH 1-456. 5 °'OH [(hydroxyamino) carbonyl] propyl} pyrrolidine- 72 2-carboxamide N- S)-l-(aminomethyl)-2-( {(1 S, 2R)-2- H N HaC OH Chiml hydroxy-1- fHH) Ht OH [(hydroxyamino) carbonyl] propyl} amino)-2-429. 5 b"o" [ (Y Y) Y] p PY}) oxoethyl]-4'-ethyl-1, 1'-biphenyl-4- 73 carboxamide Example Structure Name MH+ Y°". "'4'-ethyl-N- { (lS)-l- [ ( { (lS, 2R)-2-hydroxy-l- "+N@H-OH [(hydroxyamino) carbonyl] propyl} amino) carbo 438. 5 HsC t/O nyl] but-3-ynyl}-1, 1'-biphenyl-4-carboxamide 74 H, C OH Chiml (2S, 3R)-2-({(2S)-2-[(1, 1-biphenyl-4- ylacetyl) amino] propanoyllamino)-N, 3- 400. 4 o dihydroxybutanamide 75 OH Chlral (2S, 4R)-l- (l, 1'-biphenyl-4-ylacetyl)-4- ° N"o o"hydroxy-N- { (1S, 2R)-2-hydroxy-1_ OH [ (hydroxyamino) carbonyllpropyllpyrrohdine- ° O bo" [ (Y Y) Y] p pY} pyn. 2-carboxamide 76 H, c Chiral 4'-ethyl-N-{(lR, 2R)-2-hydroxy-1- \ N'-NN°" [ (hydroxy { [ (2_ "hydroxyethyl) amino carbonyl} amino) methyl] p ropyl}-1, 1'-biphenyl-4-carboxamide 77 H., C. oH Chira) N- ( (2R, 3R)-2- { [ (4'-ethyl-1, 1'-biphenyl-4- HOH Yl) carbonyllaminol-3-hyclroxybutyl)-N- 442. 5 ", ° hydroxymorpholine-4-carboxamide 78 on, o_ _oH A chim o 6c 0H Chim) N- ( (2R3R)-2-1 [ (4'-ethyl-1, 1'-biphenyl-4- OH Yl) carbonyllamino)-3-hydroxybutyl)-N- 455. 6 e hydroxy-4-methylpiperazine-1-carboxamide 79 HC OH Chlml N- ( (IR, 2R)-l- ITNZ'A 1 [ [ (cyclopropylamino) carbonyl] (hydroxy) amm q. 12. 5 °"o] methyl}-2-hydroxypropyl)-4'-ethYl-1, 1'- biphenyl-4-carboxamide 80 oC>, OH O Chbr31 4'-ethyl-N-{(lR, 2R)-2-hydroxy-1- HH N H<N [(hydroxy {[(pyridin-3-4 5 f"y °"y] methyl) amino] carbonyl} amino) methyl] propy 1}-1, 1'-biphenyl-4-carboxamide 81 oSczH N Chir31 4'-ethyl-N-{(lR, 2R)-2-hydroxy-1- [ (hydroxy { [ (2-pyridin-2- p "p ylethyl) amino] carbonyl} amino) methyl] propyl} 1, 1'-biphenyl-4-carboxamide 82 Example Structure Name MH+ mp _ -4'-ethyl-N- { (1R, 2R)-2-hydroxy-1- H H N H oN\J° [(hydroxy { [(4-morpholin-4-533 OR ylphenyl) amino] carbonyllaniino) methyl] propy 1}-1, 1'-biphenyl-4-carboxamide 83 OH t ° N~1^ ((2R, 3R)-2-{[(4'-ethyl-1, 1'-biphenyl-4- OH yl) carbonyl] amino}-3-hydroxybutyl)-N~1~-483. 6 hydroxypiperidine-1, 4-dicarboxamide 84 O OH i NH H 4'-ethyl-N- [2- (hydroxyamino) ethyl]-I, I'- 285. 4 biphenyl-4-carboxamide HzN 85 OH i N NH XNH~NbNH2 N- {2-[(aminocarbonyl) (hydroxy) amino] ethyl} H, C 0 4'-ethyl-1, 1'-biphenyl4-carboxami Ide 328. 4 3 86 < OH w N NHz jvj_ {2_ AJ s [(aminocarbonothioyl) (hydroxy) amino] ethyl}- 344. 4 H,, C,, () 4'-ethyl-1, 1'-biphenyl-4-carboxamide 87 H N-f2- [ (f [2- HH Y N (dimethylamino) ethyl] amino} carbonyl) (hydro 399, 5 xy) amino] ethyl}-4'-ethyl-1, 1'-biphenyl-4- carboxamide 88 w-. NH b. N N- {2-fff (2_ o cyanoethyl) amino] carbonyl} (hydroxy) amino] e 381. 4 I H, C 9'thyl}-41-ethyl-1, 1'-biphenyl-4-carboxamide 89 H IOH H 4-ethyl-N-[2-(hydroxy {[(2- o hydroxyethyl) amino] carbonyl} amino) ethyl]- 372. 4 1, 1'-biphenyl-4-carboxaniide 90 ~ OH CY N- (2-1 [ (4'-ethyl- 1, I'-biphenyl-4- o yl) carbonyl] amino} ethyl)-N- 398. 5 H3C U hydroxymorpholine-4-carboxamide 91 Example Structure Name MH+ "N- (2- { [ (4'-ethyl-1, l'-biphenyl-4- oh yl) carbonyl] amino} ethyl)-N-hydroxy-4- 411. 5 HJCspU methylpiperazine-1-carboxamide 92 p O OH eNHz N~1~-(2-{[(4'-ethyl-1, 1'-biphenyl-4- o"yl) carbonyl] amino} ethyl)-N-l- 439. 5 hydroxypiperidine-1, 4-dicarboxamide 93 o NNH N N- (2- { [ (4'-ethyl-1, 1'-biphenyl-4- gW H O yl) carbonyl] amino} ethyl)-N- 382. 5 i% c,, Oe hydroxypyrrolidine-l-carboxamide 94 0 OH ° N~2) N N-{2- 4 H o [[(cyclopropylamino) carbonyl] (hydroxy) amin 368. 4 H3C W o] ethyl}-4'-ethyl-1, 1'-biphenyl-4-carboxamide 95 vH bo ° 4-ethyl-N- {2-[hydroxy ( { [2- vJ o (methyloxy) ethyl] amino} carbonyl) amino] ethyl 386. 5 I }-1, 1'-biphenyl-4-carboxamide 96 o ? n p N- {2- [ ( { [2- han (acetylamino) ethyl] amino} carbonyl) (hydroxy) amino] ethyl}-4'-ethyl-1, 1'-biphenyl-4- carboxamide 97 0 YH 4'-ethyl-N- {2- [hydroxy ( { [3-(2-oxopyrrolidin-1 b o yl) propyl] amino} carbonyl) amino] ethyl}-1, 1'- 453. 6 biphenyl-4-carboxamide 98 y 4'-etllyl-N- [2- (hydroxy { [ (3- mu H hydroxypropyl) amino] carbonyl} amino) ethyl]-386. 5 1, 1'-biphenyl-4-carboxaniide 99 p. No-o", 4'-ethyl-N- {2- [hydroxy ( { [3- (methyloxy) propyl] amino} carbonyl) amino] eth 400. 5 "'° yl}-1, 1'-biphenyl-4-carboxamide 100 Example Structure Name MH+ ° OH SNS N-(2-{[(4'-ethyl-1, 1'-biphenyl-4- eN~N N yl) carbonyl] amino} ethyl)-N-hydroxy-l, 4'- 479. 6 0 bipiperidine-l'-carboxamide 101 y 4'-ethyl-N- [2- (hydroxy { [ (2-pyridin-2- o . ylethyl) arnino] carbonyl} amino) ethyl]-l, 1'-433. 5 biphenyl-4-carboxan) ide 102 OH N "Y 4'-ethyl-N- [2- (hydroxyl [ (pyridin-3- 0 ylinethyl) amino] carbonyl} amino) ethyl]-1, 1'- 419. 5 biphenyl-4-carboxamide 103 4'-ethyl-N- [2- (hydroxy { [ (4-morpholin-4- (H neo phenyl) amino] carbonyl} amino) ethyl]-l, 1'- 489. 6 "'° 'biphenyl-4-carboxamide 104 OH 9 ~2H b N-(2-{[(4'-ethyl-1, 1'-biphenyl-4- "NUN yl) carbonyl] amino} ethyl)-N, 3- 412. 5 H3Cgv dihydroxypiperidine-l-carboxamide 3 105 N-12- [I [ (3- n Y aminocyclohexyl) aminolcarbonyl} (hydroxy) a 425 5 mino] ethyl}-4'-ethyl-1, 1'-biphenyl-4- carboxamide 106 < N N N {2 [ { [(2 g J H O aminoethyl) amino] carbonyl} (hydroxy) amino] e 371. 4 H3C> » thyl}-4'-ethyl-1, 1'-biphenyl-4-carboxamide 107 9H vHN~2) N NH2 N-{2-[{[(3- o aminopropyl) amino] carbonyl} (hydroxy) amino 385. 5 I ] ethyl}-4'-ethyl-1, 1'-biphenyl-4-carboxamide 108 1, 1-dimethylethyl3- ( { [ (2- { [ (4'-ethyl-1, 1'- ° °H ° °", N,, _Nyo, biphenyl-4- ' ° ° yl) carbonyl] amino} ethyl) (hydroxy) amino] carb onyl} amino) propylcarbamate 109 Example Structure Name MH+ NJaF 4-ethyl-N- {2-[( { [(4- HzN fluorophenyl) methyl] amino} carbonyl) (hydrox 436. 5 y) amino] ethyl}-1, l'-biphenyl-4-carboxamide 110 OH NgF N-(2-{[(4'-ethyl-1, 1'-biphenyl-4- . y F yl) carbonyl] amino} ethyl)-N-hydroxy-3- H, Cs [(trifluoroacetyl) amitio] pyrrolidine-1 ~ carboxamide 111 ° N~2) N N H2 N- {2- [ { [ (4-aminothien-3- yl) amino] carbonyl} (hydroxy) amino] ethyl}-4'- 425. 5 H3Cs J ethyl-1, 1'-biphenyl-4-carboxamide 112 N"4'-ethyl-N- (2- {hydroxy [ (piperidin-3- f 4 o sG ylamino) carbonyl] amino} ethyl)-1, 1'-biphenyl-411. 5 HaCJ 4-carboxamide 113 4'-ethyl-N- (2- {hydroxy [(piperidm-4- 0'OIH O NH ylamino) carbonyl] amino} ethyl)-1, l'-biphenyl-411. 5 HC, O-e 4-carboxamide 114 ~N NHJS 4'-ethyl-N-[2-(hydroxy {[(piperidin-2- o b ylmethyl) amino] carbonyl} amino) ethyl]-l, 1'- 425. 5 ", c biphenyl-4-carboxamide 115 ~2 4'-ethyl-N- [2- (hydroxy { [ (piperidm-3- Y yhnethyl) amino] carbonyl} amino) ethyl]-1, 1'- 425. 5 biphenyl-4-carboxamide 116 N 3-aniino-N- (2-1 [ (4'-ethyl-1, 1'-biphenyl-4- (+ yl) carbonyl] amino} ethyl)-N- 397. 5 o hydroxypyrrolidine-1-carboxamide 117 1, 1-dimethylethyl 3-[( { [(2- { [(4'-ethyl-1, 1'- biphenyl-4- H, c-lr TCH, 3 yl) carbonyl] amino} ethyl) (hydroxy) amino] carb onyl} amino) methyl] piperidine-1-carboxylate 118 Example Structure Name MH+ on OH 1, 1-dimethylethyll- { [ (2- { [ (4'-ethyl-1, 1'- NyND-0 y0 biphenyl-4- 0 0xCH 1 497. 6 He JL<J n, c en, yl) carbonyl] amino} ethyl) (hydroxy) ammo] carb onylC CHr Y) Y]-3-ylcarbamate 119 119 I, C ONH Chiral WH 4'-ethyl-N- [ (IS, 2R)-2-hydroxy-l- (1 [2- (hydroxyamino) ethyl] amino} carbonyl) propyl]- 386. 5 HCsJU 1-biphenyl-4-carboxamide 120 oH ch., N- { (1S, 2R)-1- [ ( {2- [ (aminocarbonyl) (hydroxy) amino] ethyl} amino 429. 5 e e °) carbonyl]-2-hydroxypropyl}-4'-ethyl-1, 1'- biphenyl-4-carboxamide 121 oH ch. N- { (1S, 2R)-1- [ ( {2- p'NtJ''NH2 [ (aminocarbonothioyl) (hydroxy) amino] ethyl} 445. 6 li, oH mino) carbonyl]-2-hydroxypropyl}-4'-ethyl-1, 1' biphenyl-4-carboxamide 122 4'-ethyl-N- [(1 S, 2R)-2-hydroxy-1-( { [2- ~t°X ; Ohir I (hydroxy {[(2- 'NJNfN °H e H T°I oH G hydroxyethyl) amino] carbonyl} amino) ethyl] am 473. 5 0 lino) carbonyl) propyl]-l, l'-biphenyl-4- 123 carboxamide 1 o o tHH o chznl 4'-ethyl-N-{(lS)-6-hydroxy-1-[(lR)-l- NN"1N~O OH hydroxyethyl] 2, 7-dioxo-11oxa3, 6, 8- 487. 6 , J 0 OH".-,. H11tt.-T-1 O/. b H, oga triazadodec-1-yl}-1, 1'-biphenyl-4- carboxamide 124 4'-ethyl-N- { (1S)-6-hydroxy-1- [ (1R)-1- N"JTN~N OHs hydroxyethyl]-l l-methyl-2, 7-dioxo-3, 6, 8, 11- OH 500. 6 Hao r o OH tetraazadodec-l-yl}-l, l'-biphenyl-4- carboxamide 125 ,, 4'-ethyl-N- { (lS)-6-hydroxy-l- [ (lR)-l- g4, H, H hydroxyethyl] 2, 7, 12-trioxo-3, 6, 8, 11- J'"0 OH"0 ni1. t.. T. t.. 014. 0 H, o ¢> tetraazatridec-1-yl}-1, 1'-biphenyl-4- carboxamide 126 4'-ethyl-N- { ( 1 S, 2R)-2-hydroxy-1- [ ( {2- y°"o o. [hydroxy ( { [3- (2-oxopyrrolidin-1- i p'1or oH a V yl) propyl] amino} carbonyl) amino] ethyl} amino 554. 7 i oH) carbonyl] propyl}-1, 1'-biphenyl-4- 127 carboxamide Example Structure Name MH+ oHzo on, . N- { (1S, 2R)-1- [ ( {2- [ { [ (2- ~OJ4HXW N, tN N cyanoethyl) amino] carbonyl} (hydroxy) amino] e 482. 6 H, cJSi thyl} amino) carbonyl]-2-hydroxypropyl}-4'- ethyl-1, 1'-biphenyl-4-carboxamide 128 , ° oH ° cn, m N- { (1S, 2R)-1- [ ( {2- p [ [ (cyclopropylaniino) carbonyl] (hydroxy) 0 OH amm 469, 6 o] ethyl} amino) carbonyl]-2-hydroxypropyl}-4'- ethyl-1, 1'-biphenyl-4-carboxamide 129 0 Chimi N-12- [ ( (2S, 3R)-2-1 [ (4'-ethyl-1, 1'-biphenyl-4- 'kN yl) carbonyl] amino}-3- OH hydroxybutanoyl) amino] ethyl}-N- hydroxypyrrolidine-l-carboxamide 130 ffic OH Chl. 1 N-12- [ ( (2S, 3R)-2-1 [ (4'-ethyl-1, 1'-biphenyl-4- N) ; yl) carbonyl] amino}-3- n. c AJ hydroxybutanoyl) amino] ethyl}-N- 131 hydroxymorpholine-4-carboxamide 131 °"°"", N- {2- [ ( (2S, 3R)-2- { [ (4'-ethyl-1, 1'-biphenyl-4- p-b""-1 yl) carbonyl] amino}-3- C'OH N-C. % hydroxybutanoyl) amino] ethyl}-N-hydroxy-4- methylpiperazine-1-carboxamide 132 oxo .,, 4'-ethyl-N- [ (lS, 2R)-2-hydroxy-l- ( { [2- , < X (rH1 1 (hYdr°XY {[(pyridin3 H, o 1 o OH ylmethyl) amino] carbonyl} amino) ethyl] amino} carbonyl) propyl]-1, 1'-biphenyl-4-carboxamide 133 c OHH o N ChltI 4'-ethyl-N-[(lS, 2R)-2-hydroxy-1-({[2- vH>t IJ4NH<3 (hydroxy {[(2-pyridin-2- ylethyl) amino] carbonyl} amino) ethyl] amino} ca rbonyl) propyl]-1, 1'-biphenyl-4-carboxamide 134 IHLHI IH-oH""' Ho_q °H ° 3-chloro-N- { (lS, 2S)-2-hydroxy-l- °l [ (hydroxyamino) carbonyl] propyl}-4- 357. 7 I Cl ro>F N FNi [(trifluoromethyl) oxy] benzamide 135 F/F H Chlral 13C-_ OH N OH N-I (IS, 2R)-2-hydroxy-l- mu [ (hydroxyamino) carbonyl] propyl}-4- { [ (3- 390. 4 nitrophenyl) methyl] oxy} benzamide 136 oxo Example Structure Name MH+ 0 H CMrif 0Chiral M-/°" Xo (4R)-2- (4-fluoro-3-prop-2-enylphenyl)-N- hydroxy-4, 5-dihydro-1, 3-oxazole-4- 265. 3 J carboxamide 137 8H2 ... oH3C OH Chiraì H 3-fluoro-N- { (lS, 2R)-2-hydroxy-1- N oH [ (hydroxyamino) carbonyl] propyl}-4- 287. 3 I H 138 o (methyloxy) benzamide 138 oH3C OH Chirai _ 4- (but-3-enyloxy)-N-I (lS, 2R)-2-hydroxy-l- 309. 3 H c% o I "o [ (hydroxyamino) carbonyl] propyl} benzamide 2 139 oH3C OH Chral F N. 3-bromo-5-fluoro-N- { ( 1 S, 2R)-2-hydroxy-1- H2C00XJ H o [(hydroxyamino) carbonyl] propyl}-4- (prop-2- 392. 2 enyloxy) benzamide 8r 140 HO H CH Chiral ° H3 N OH 4-fluoro-N-I (lS, 2S)-2-hydroxy-l- F>9 [(hydroxyamino) carbonyl] propyl}-3-prop-2-297. 3 enylbenzamide t 141 CH2 NC OH Chiral NN'OH N- { (lS, 2R)-2-hydroxy-1- Hc° F H O [ (hydroxyamino) carbonyl] propyl) 4- (prop-2- 363. 3 enyloxy)-3- (trifluoromethyl) benzamide F F 142 oH3C OH Chiral H N- { (lS, 2R)-2-hydroxy-1- NOH ( (hydroxyamino) carbonyl] propyl}-4- 269. 3 H3Cso o (methyloxy) benzamide 143 H3C OH Chiral o''°' N- { (lS, 2R)-2-hydroxy-l- 0) 34 HX OH [(hydroxyamino) carbonyl] propyl}-3- 331. 3 U-H0 (phenyloxy) benzamide 144 F F OH Chiral d3CH N- { (lS, 2R)-2-hydroxy-l- N'OH [ (liydroxyamino) carbonyl] propyl}-4- 0 i (methyloxy)-3- H C [ (trifluoromethyl) oxy] benzamide 145 ExampleStructureNameMH+ H Chiral o H N- { (lS, 2S)-2-hydroxy-1- F I N N-O [ (hydroxyamino) carbonyl] propyl}-4- 323. 2 H O H [ (trifluoromethyl) oxy] benzamide 146 146 HChiral I o=3Cu¢O H N-{(lS, 2R)-2-hydroxy-1- F'U, N'N, o [ (hydroxyarnino) carbonyl] propyl}-4-323. 2 1 i H O H [ (trifluoromethyl) oxy] benzamide 147 F 147 13C OH Chiral < X<N N-{(lS, 2R)-2-hydroxy-1- F F oW H O [(hydroxyamino) carbonyl] propyl}-4- 307. 2 (trifluoromethyl) benzamide F 148 (Y., C OH Chiral F NNHOH 3, 4-difluoro-N-{(2R)-2-hydroxy-1-2 2 H H o [(hydroxyamino) carbonyl] propyl} benzamide F 149 o3C/t OH Chiral N-{(lS, 2S)-2-hydroxy-l- N' [N'OH [ (hydroxyamino) carbonyl] propyl}-4- 269. 3 3 vo ° (methyloxy) benzamide 150 C H ON Chlral N- { ( 1 S, 2R)-2-hydroxy-1- >9 ; H o OH [(hydroxyamino) carbonyl] propyl}-4'-propyl- 357. 4 1, 1'-biphenyl-4-carboxamide n, c 151 G3C H OH ChiC3l. O° N- { (1 S, 2R)-2-hydroxy-1- 0OH [ (hydroxyamino) carbonyl] propyl}-4'-propyl- 357. 4 1, 1'-biphenyl-4-carboxamide 152 H Chircil u-H Chira ! N- N- OH S, 2R)-2-hydroxy-1- H OH [ (hydroxyamino) carbonyl] propyl}-4- F 9i O [trifluoro (methylidene)-lambda~6~- --'CH sulfanyl] benzamide 153 H Chiral H C OH ? LNHOH N- { (lS, 2R)-2-hydroxy-l- g N [ (hydroxyamino) carbonyl] propyl} benzamide ° 154 Example Structure Name MIl+ Chiral oH3CeOH , 14 NHOH N- {(l S, 2R)-2-hydroxy-1- N-lr [(hydroxyamino) carbonyl] propyl}-1, 1'- 315. 3 "biphenyl-4-carboxamide 155 Chiral H3C OH Jt NHOH 3-bromo-N-{(1 S, 2R)-2-hydroxy-1- H H p [ (hydroxyamino) carbonyl] propyl}-4- 348. 2 OH, C-P (methyloxy) benzamide Br 156 H Chiral HCtOH NHOH 4-fluoro-N- { (lS, 2R)-2-hydroxy-l- , 9i o [(hydroxyamino) carbonyl] propyl}-3- (prop-2- 313. 3 o enyloxy) benzaride 157 iCH2 H Chiral HCOH F NHOH 2, 3, 5, 6-tetrafluoro-N- { (1S, 2R)-2-hydroxy-1- JJ M o [ (hydroxyamino) carbonyl] propyl}-4-prop-2- 351. 3 F enylbenzamide H C F 158 H Chiral HC OH F NHOH 3-fluoro-N- { (1S, 2R)-2-hydroxy-1- N [ (hydroxyanlino) carbonyllpropyl}-5- 325. 2 Y (trifluoromethyl) benzamide 159 CF3 Chiral 3OH -NHOH 4-bromo-2-fluoro-N-I (lS, 2R)-2-hydroxy-l- 336. 1 WHN H [(hydroxyamino) carbonyl] propyl} benzamide H0 160 Chlral HO-OH 03-NHOH N- {(l S, 2R)-2-hydroxy-1- H o [ (hydroxyamino) carbonyl] propyl}-4- 331. 3 (phenyloxy) benzamide 161 161 H 0 H NHOH 4- (dimethylamino)-N- { (1S, 2R)-2-hydroxy-1- 282. 3 H3C-'CH H O [(hydroxyamino) carbonyl] propyl} benzamide CH, 162 o NHOH N 2- [3-fluoro-4- (methyloxy)-5-prop-2- H2C HO enylphenyl]-N-hydroxy-4, 5-dihydro-1, 3-295. 3 OH3CS oxazole-4-carboxamide 163 F Example Structure Name MH+ CP- Chirac 1 S 2R-2 h drox-- 0 3c oH N- { ( )-Y y 1 +°At NHOH [ (hydroxyamino) carbonyllpropyll-5- [3- 373. 3 /H H o (trifluoromethyl) phenyl] furan-2-carboxamide 164 H C H °H Chtral H. C'OH o 3-NHOH 4-1 [ (lE)-1, 2-difluorobuta-1, 3-dienyl] oxy}-N- CjH2 @N ~ {(lS, 2R)-2-hydroxy-1-343. 3 , O [(hydroxyamino) carbonyl] propyl} benzamide F 165 H Chiral H C ~ OH N-{(lS, 2R)-2-hydroxy-1- A 4N/jF [(hydroxyamino) carbonyl] propyl} quinoline-2-290. 3 H o carboxamide 166 ou O OH N II N- [2- (hydroxyamino)-1- (hydroxymethyl)-2- < oxoethyl]-l, l'-biphenyl-4-carboxamide 301. 3 i 167 CH Chtral t . NHOH N- { (lS, 2S)-2-hydroxy-l-' H H o [ (hydroxyamino) carbonyl] propyl}-1, 1'- 315. 3 biphenyl-4-carboxamide i 168 H Chiral HO OH O NHOH N- { ( 1 S, 2R)-2-hydroxy-1- H 0 [ (hydroxyamino) carbonyl] propyl}-2'-methyl-329. 4 1, 1'-biplienyl-4-carboxamide 169 CH Chiral 0H 6H ; g, NHOH N- {(l S, 2S)-2-hydroxy-1- vH H [(hydroxyamino) carbonyl] propyl}-4- 307. 2 F (trifluoromethyl) benzamide F 170 H Chiral F oH3C OH 4-fluoro-N-{(lS, 2R)-2-hydroxy-1- /NHOH [(hydroxyamino) carbonyl] propyl}-3- 325. 2 F H0 (trifluorometliyl) benzamide F 171 H Chiral ON3C OH M, OH N-f (I S, 2R)-2-hydroxy- I- o [ (hYdroxYamino) carbonYllpropyll-4-1 [ (3- 390. 4 nitrophenyl) oxy] methyl} benzamide 4 172 oo Exam le Structure Name MH+ SH Chiral N, OH N- [ (IR)-2- (hydroxyamino)-i- F JYH O (mercaptomethyl)-2-oxoethyl]-4-325. 3 173 FWO [(trifluoromethyl) oxy] benzamide F 173 H Chiral 0 3c-o H N- { (1S, 2R)-2-hydroxy-1- 0 N ; r NOH 1 (hydroxyamino) carbonyl] propyl}-1, 3- 283. 3 H p benzodioxole-5-carboxamide z 174 H3C-OH' H C' :' OH 0 N, N- { (1S, 2R)-2-hydroxy-1- F li<H H O [(hydroxyamino) carbonyl] propyl}-6- 308. 2 F F (trifluoromethyl) pyridine-3-carboxamide F 175 OH ° H N- {3-hydroxy-1- N- N, OH [ (hydroxyamino) carbonyl] propyll-4- 323. 2 FXO ° [(trifluoromethyl) oxy] benzamide 176 F F OH ° H N- {3-hydroxy-1- N- N, OH [ (hydroxyamino) carbonyl] propyl}-1, 1'- 315. 3 ° biphenyl-4-carboxamide 177 H China ! °H3CaoH* N- { S, 2R)-2-hydroxy-1- y X-T OH [(hydroxyamino) carbonyl] propyl}-4- 345. 4 [hydroxy (phenyl) methyl] benzamide OH 178 H Chtm ! H, c oH t6C N- OH (lS, 2R)-2-hydroxy-l- » Nh ijo OH [(hydroxyamino) carbonyl] propyl}-4- [ ( {4- i trifluorometliyl oxy] phenyl} oxy) methyl] benz amide 17amide H 9 H, Chiral 4- [ ( {4-bromo-2- OXF F'lX [(trifluoromethyl) oxy] phenyl} oxy) methyl]-N- 508. 3 fuzz {(lS, 2R)-2-hydroxy-1- 0 180 [ (hydroxyamino) carbonyl] propyl} benzamide 180'"" H China ! HaC OH N'-H'N'OH N- { (1S, 2R)-2-hydroxy-1- it [(hydroxyamino) carbonyl] propyl}-3'-nitro-1, 1'360. 3 I biphenyl-4-carboxamide 181 oo Example Structure Name MH+ H Chira) HO OH o OH 4-bromo-N-{(1 S, 2R)-2-hydroxy l- JYH H O [(hydroxyamino) carbonyl] propyl} benzamide 318. 1 Bu 182 HChiral oN, N- { (lS, 2R)-2-hydroxy-1- H0 [ (hydroxyamino) carbonyl] propyl}-4'-345*4 c, o I (methyloxy)-1, 1'-biphenyl-4-carboxamide 1 3 H Chiral H Chira) H. C-. OH N- { (lS, 2R)-2-hydroxy-l- , <H H O [(hydroxyamino) carbonyl] propyl}-4'-399 3 Oti [(trifluoromethyl) oxy]-1, 1'-biphenyl-4- 0 F-f-F carboxamide 184 4 H Chiral °H3C OHH ° r H NNOH 4'- (ethyloxy)-N-f (lS, 2R)-2-hydroxy-1- o C [(hydroxyamino) carbonyl] propyl}-1, 1'- 359. 4 biphenyl-4-carboxamide 185"'c H Chiral HgCOH NN, OH N- { (lS, 2R)-2-hydroxy-l- < H o [(hydroxyamino) carbonyl] propyl}-4- {5- [ (Z)- 364. 4 Hts (hydroxyimino) methyl] thien-2-yl} benzamide H 186 N-OH Choral 3'- (ethyloxy)-N- { (1S, 2R)-2-hydroxy-1- H3cvo i Hlol OH [ (hydroxyamino) carbonyl] propyl}-1, 1'- 359. 4 biphenyl-4-carboxamide 187 OH Chiral O HN O (2R, 3R)-N, 3-dihydroxy-1- ( {4- N", oH [ (trifluoromethyl) oxy] phenyl} carbonyl) pyrroli 335. 2 F Xj dme-2-carboxammde 188 F F OH N N. CH N- [2- (hydroxyamino)-1- (hydroxymethyl)-2- HC. JL"0 oxoethyl]-3- (l-methylethyl)-4- 297. 3 (methyloxy) benzamide 189 H3C CH3 OH 0H H N-1 N'OH N- [2- (hydroxyaniino)-l- (hydroxymethyl)-2- wo o oxoethyl]-3-(1-methylethyl)-4-(prop-2-323. 4 enyloxy) benzamide H, C CH, 190 Example Structure Name MH+ OH 0 o OH O N-[2-(hydroxyamino)-l-(hydrOxymethyl)-2- ° oxoethyl]-4- (methyloxy)-3-propylbenzamide 191 H Chlral HCOH < OH N-I (lS, 2R)-2-hydroxy-l- f H o [(hydroxyamino) carbonyl] propyl}-4'-361 4 (methylthio)-1, 1'-biphenyl-4-carboxamide 192 H, c 192 H Chiral O C = OH 0 H 5-bromo-N- { (lS, 2R)-2-hydroxy-l- X-t OH [(hydroxyamino) carbonyl] propyl} thiophene-2- 324. 2 s H O carboxamide 193 Br H chie H, COH nHJcXH N- {(1 S, 2R)-2-hydroxy-1- H0 [ (hydroxyamino) carbonyllpropyll-5-14- 405. 4 > [(trifluoromethyl) oxy] phenyl} thiophene-2- o carboxamide 194 F F H Chiral 0 3C-oH N- { (1S, 2R)-2-hydroxy-1- NOH 1 (hydroxyamino) r-arbonyl] propyll-l- 279. 3 p H O benzofuran-2-carboxamide 195 H Chiraì oH3C-OH N A RM'OH N-I (IS, 2R)-2-hydroxy-l- &s H o [(hydroxyamino) carbonyl] propyl}-5-321. 4 phenylthiophene-2-carboxamide sr chie HChiral 0NN, OH 4'- (dimetliylamino)-N-I (lS, 2R)-2-hydroxy-l- \ I, H H O [ (hydroxyamino) carbonyl] propyl}-1, 1'- 358. 4 biphenyl-4-carboxamide 197 cl, H Chiraì HO-OH | Hj O (2S, 3R)-N, 3-dihydroxy-2-[({2- OH [ (trifluoromethyl) oxy] phenyl} acetyl) amino] bu 337. 3 O H O tanamide 19F 198 H Chira) HCt--OH NN'OH 5- [4- (ethyloxy) phenyl]-N- { S, 2R)-2-hydroxy /<s o l-[(hydroxyamino) carbonyl] propyl} thiophene-365. 4 [ (Y Y) Y] P pY} p oH 2-carboxamide H3C^O 199 Example Structure Name _ ME1+ H Chlral v °° _oH 5- [3- (ethyloxy) phenyl]-N- { (1S, 2R)-2-hydroxy s0 1- [ (hydroxyamino) carbonyl] propyl} thiophene- 365. 4 H3C Og 2-carboxamide 200 0Chiral FXF » (4R)-N-hydroxy-2-{2'-[(trifluoromethyl) oxy]- O F O 1, 1'-biphenyl-4-yl}-4, 5-dihydro-1, 3-oxazole-4-367. 3 carboxamide 201 H Chiraì oH3C OH OH N-I (IS, 2R)-2-hydroxy-l- o [ (hydroxyamino) carbonyl] propyl}-4'- 345. 4 (hydroxymethyl)-1, 1'-biphenyl-4-carboxamide 202 oH H Ch ! ra ! HC-OH N- { (1S, 2R)-2-hydroxy-1- +h [(hydroxyamino) carbonyl] propyl}-4- {5- [ (4- s 433. 5 s methylpiperazin-1-yl) methyl] thien-2- yl} benzamide 203 cl, t H Ch ! ra ! N- { (lS, 2R)-2-hydroxy-1- nl le Ht [(hydroxyamino) carbonyl] propyl}-4- { [4-373. 4 (methyloxy) phenyl] carbonyl} benzamide o 204 H Chiraì oH3C OH o3 m, N-I (lS, 2R)-2-hydroxy-l- H H ° [ (hydroxyamino) carbonyl] propyl}-4- [ (E)- 343. 4 phenyldiazenyl] benzamide 205 Chiral H F N oH (4R)-N-hydroxy-2- {4- (methyloxy)-3- F---o [ (trifluoromethyl) oxy] phenyl}-4, 5-dihydro-1, 3 321. 2 oxazole-4-carboxamide 206 3 O 206 H Chlral H3C OH 0M, OH 4'-ethyl-N-I (IS, 2R)-2-hydroxy-l- N H0 [ (hydroxyamino) carbonyl] propyl}-l, l'- 343. 4 H, C, biphenyl-4-carboxamide 3 207 H Chiral HO OH 4 WNoH N-{(lS, 2R)-2-hydroxy-1- Po [(hydroxyamino) carbonyl] propyl}-4'-383. 3 FCW (trlifluoromethyl)-1, 1'-biphenyl-4-carboxamide 208 Example Structure Name H Chira) H3c OH g N s OH 5-(4-ethylphenyl)-N- { (1 S, 2R)-2-hydroxy-1- H o [ (hydroxyamino) carbonyl] propyl} thiophene-2- 349. 4 carboxamide H09 209 H Chirac HCOH _ . oH N- { (lS, 2R)-2-hydroxy-1- "o [ (hydroxyamino) carbonyl] propyl}-5- [4- 351. 4 (methyloxy) phenyl] thiophene-2-carboxamide H3C. 0 210 H Chtra) HCOH ° XN N- {(l S, 2R)-2-hydroxy-1- H0 [ (hydroxyamino) carbonyllpropyl}-5- [4- 367. 5 e (methylthio) phenyl] thiophene-2-carboxamide H, C 211 Chiral OH3C OH o3 M, N-I (lS, 2R)-2-hydroxy-l- 0. H0 [ (hydroxyamino) carbonyl] propyl}-5- (3- 366. 4 nitrophenyl) thiophene-2-carboxamide 212 H Chiraì 3C-OH, o 1 N- {(l S, 2R)-2-hydroxy-1-' [ (hydroxyamino) carbonyl] propyl}-4-oxo-4H-307. 3 I I chromene-2-carboxamide 213 0 O HO CHs 0HO CH N- [l- [ (hydroxyaniino) carbonyl]-l- Fu/F m H WNH (hydroxymethyl)-2-methylpropyl]-4-351. 3 [ (trifluoromethyl) oxy] benzamide 214 0 0 H N- [2-hydroxy-3- (hydroxyamino)-3-oxopropyl] 301. 3 i OH OH 1, 1'-biphenyl-4-carboxamide 215- H Chiral C H CH Chiral b, N- { (1S, 2R)-2-hydroxy-1- o oH [ (hydroxyamino) carbonyl] propyl}-4- [ (E)-2- 341. 4 U phenylethenyl] benzamide 216 Chiral HC OH N- { (1S, 2R)-2-hydroxy-1- H0 f (hydroxyamino) carbonyllpropyll-9H- 327. 4 fluorene-2-carboxamide 217 Exam le Structure Name MH+ H Chiral HC OH oH3CX 4-[( {(l S, 2R)-2-hydroxy-1- H [ (hydroxyamino) carbonyl] propyl} amino) carbo 359. 3 HO nyl]-1, 1'-biphenyl-4-carboxylic acid 218 OH O H S ) NsOH N-[2-(hydroxyamino)-1-(hydroxymethyl)-2- Hzco oxoethyl]-4- (prop-2-enyloxy)-3- 323. 4 propylbenzamide 219 CH3 H Chiral ° 3 t H N-{(lS, 2R)-2-hydroxy-1- lX N°H [(hydroxyamino) carbonylgpropyl}-4-365. 1 iodobenzamide 220 220 Chiral H3C-OH CX H sOH 4'-hydroxy-N- {(1 S, 2R)-2-hydroxy-1- I H0 [ (hydroxyamino) carbonyl] propyl}-1, 1'- 331. 3 HOD biphenyl-4-carboxamide Ho 221 Chiral HIC = OH N, 6-bromo-N- { (lS, 2R)-2-hydroxy-1- I+H HT OH [(hydroxyamino) carbonyl] propyl} pyridine-2-319. 1 carboxamide 222 Br H Chiral oH3C O H X Ng N- {(1 S, 2R)-2-hydroxy-1- . N [ (hydroxyamino) carbonyl] propyl}-6- 316. 3 phenylpyridine-2-carboxamide 223 Li Chiral HCt-OH 0. =m 4'-butyl-N- { (l S, 2R)-2-hydroxy-l- ~, @Nt H O [(hydroxyamino) carbonyl] propyl}-l, l'-371. 4 biphenyl-4-carboxamide HzN 224 claim HC-OH NOH 4'- (I, I-diinethylethyl)-N-I (lS, 2R)-2-hydroxy- ""0 1- [ (hydroxyamino) carbonyl] propyl}-1, 1'- 371. 4 H3Cw biphenyl-4-carboxamide 225 3 225 H Chiral HgCOH 03 1t'HN^oH N-{(lS, 2R)-2-hydroxy-1- CH S 0OH [ (hydroxyamino) carbonyl] propyl}-5- [3- 351. 4 (methyloxy) phenyl] thiophene-2-carboxamide 226 ExampteStructureNameMH+ H Chloral 1, c = OH . 4'- [ ( { (lS, 2R)-2-hydroxy-l- -"NH0 1 (hydroxyamino) carbonyl] propyl} amino) carbo 411. 3 Ho- HÓ o-W nyl]-1, 1'-biphenyl-4-yl dihydrogen phosphate Ha 227 H Chiral H, C = OH ° 3 ; HN N-ethyl-N-{(lS, 2R)-2-hydroxy-1- JL ° [ (hydroxyanuno) carbonyl] propyl}-l, l'- 386. 4 H'°vp i % [ (Y Y) Y] h pY} biphenyl-4, 4'-dicarboxamide 228 cam o3c0NH, N- [ (lS, 2R)-l- (hydrazinocarbonyl)-2- gß N ~ N 2 hydroxypropyl]-4'-propyl-1, 1'-biphenyl-4-356 *4 carboxamide H3C 229 Choral °H3C O 0c0 H { ( 1 S, 2R)-2-hydroxy-1- vH H O C 3 [(melhylarnino) carbonyl] propyl}-4'-propyl-1, 1' 355. 4 I FI biphenyl-4-carboxamide 230 1 230 Ho0 H3C O. 0& N,, H. Zinocarbonyl)-2- H/"O'NHZ hYdt'oxypropyl]-4- (methyloxy) benzamide 268. 3 H3C. ° 231 H Chlral HCOH S-N (2S, 3R)-2- [ (1, 1'-biphenyl-4-ylsulfonyl) amino]- p H'H TOI °H N, 3-dihydroxybutanamide 351. 4 232 H Chiral HC'-OH ? H, 4-hydroxy-N-I (lS, 2R)-2-hydroxy-l- N, N0 H [ (hydroxyaniino) carbonyl] propyl} benzamide HOES 0 233 H Chiral H Chiral H3C OH ° gNH 3'-cyano-N- {(1 S, 2R)-2-hydroxy-1- NX XHN H o [(hydroxyamino) carbonyl] propyl}-1, 1'- 340. 3 biphenyl-4-carboxamide 234 H Chlral 03 OH 1, 1-dimethylethyl (14- [ (I (l S, 2R)-2-hydroxy- 1 jrTM °" [ (hydroxyamino) carbonyl] propyl} ammo) carbo 369. 4 [ (Y Y) Y] P pY}) H, c 1° nyl] phenyl} oxy) acetate 235 Example Structure Name MH+ H Chiral 0 H3C OH (2S, 3R)-2- [ (1, 1'-biphenyl-4- S-N OH sulfonyl) (metliyl) amino]-N, 3- 365. 4 O ° CH3 ° dihydroxybutanamide 236 °c H oH i N-f (1S, 2R)-2-hydroxy-1- i iv HX [(hydroxyamino) carbonyl] propyl}-3'-[(Z)- (hydroxyimino) methyl]-4- (methyloxy)-1, l'- H3c-o biphenyl-4-carboxamide 237 HChiral HC OH N, N- { lS, 2R)-2-hydroxy-1- wH H O [(hydroxyamino) carbonyl] propyl}-4-358. 4 [ (phenylcarbonyl) amino] benzamide 238 t OH N ° N-hydroxy-2- [3- (l-methylethyl)-4- (prop-2- H enyloxy) phenyl]-4, 5-dihydro-1, 3-oxazole-4- 305. 3 ° T carboxamide 239 H3C CH3 H Chiral OH C OH vH ; ; CH3 4'-butyl-N-{(lS, 2R)-2-hydroxy-1- f w [(methylamino) carbonyl] propyl}-1, 1'-biphenyl 369. 5 4-carboxamide CH, 240 H Chiraì °H3C OH M, OH N-I (lS, 2R)-2-hy&oxy-l- I "o [ (hydroxyamino) carbonyl] propyl}-4- (5- 330. 4 H tN methylpyridin-2-yl) benzamide HIC 241 H Chira) o 3 H 5-bromo-N-I (lS, 2R)-2-hydroxy-l- B NN'OH [ (hydroxyamino) carbonyl] propyl} pyridine-3- 319. 1 carboxamide N 242 H Chiral HgCOH N, N-f (lS, 2R)-2-hydroxy-l- H 0 [ (hydroxyamino) carbonyl] propyl}-4-pyridin-3 316. 3 ylbenzamide 243 N-{(lR, 2R)-2-hydroxy-1- H, C H 0 HCHChiral [Olydroxyamino) carbonyl] propyll-Nl- HW H H wNOH {(lS, 2R)-2-hydroxy-l-475 5 [(hydroxyamino) carbonyl] propyl}-1, 1'- 244 biphenyl-4, 4'-dicarboxamide Example Structure Name MH+ HChiral H3C OH M, OH (2S, 3R)-N, 3-dihydroxy-2- [ ( {4- [ (E)-2- I N Ao phenylethenyllphenyl) methyl) amino] butanami 327*4 de 245 H Chiral HC OH '4 4-bromo hen 1 sulfon 1 amino-N- \ o N b. o"- { [ ( P Y) Y]} ° : S° I ""o { (1S, 2R)-2-hydroxy-1- 473. 3 I ' [ (hydroxyamino) carbonyl] propyl} benzamide 246 246 HHChi. ? 1, 1-dirnethylethyl 4- (14- [ (I (lS, 2R)-2-hydroxy. , ° oH p"b. oH 1-439. 5 "p' [ (hydroxyamino) carbonyl] propyl} amino) carbo nyl] phenyl} amino)-4-oxobutylcarbamate 247 li Chlral T°'M 4- [ (4-aminobutanoyl) amino]-N- { (lS, 2R)-2- O HNAW OH hydroxy-1-339. 4 H-N A J' H"o'' b [ (hydroxyamino) carbonyl] propyl} benzamide 248 ho » H '"'1, 1-dimethylethyl {4'- [ ( { (lS, 2R)-2-hydroxy-l- [ (hydroxyamino) carbonyl] propyl} amino) meth 430. 5 ° °"yl]-1, 1'-biphenyl-4-yl} methylcarbamate 249 </-0-4''OH N-f (IS, 2R)-2-hydroxy-l- H XÑ [(hydroxyarmno) carbonyl] propyl}-4-pyrimidin 317. 3 O vOH 5-ylbenzamide 250 P 1, 1-dimethylethyl5- {4- [ ( { (1S, 2R)-2-hydroxy- 3C ", ° °ti, /'o"416. 4 Han b, °" [ (hydroxyamino) carbonyl] propyl} amino) carbo nyl] phenyl} pyridine-3-carboxylate 251 P Chira) HO"C"5- {4- [ ( { (1S, 2R)-2-hydroxy-1- ' " [ (hydroxyamino) carbonyl] propyl} amino) carbo 360. 3 _OH a 0'OH nyllphenyllpyridine-3-carboxylic acid 252 252 09,, Chiral F+F ^ OH (4S)-N-hydroxy-2-{4-(methyloxy)-3- 0 [ (trifluoromethyl) oxy] phenyll-4, 5-dihydro-1, 3. 321. 2 oxazole-4-carboxamide H3C. C 253 ° Example Structure Name MH+ H3Cs H Chiml oH (2S, 3R)-2- ( { [4'- (aminomethyl)-1, 1'-biphenyl-4 330. 4 H'H NOH yl] metilyl} aminO)-N, 3-dihydrOXybutanamide 0oh 254 H Chiral H3C (3S)-l-hydroxy-3- [ (IR)-l-hydroxyethyl]-4- (14 Ho w N r [ (E)-2- <1 = Y OH phenylethenyl] phenyl} methyl) piperazine-2, 6- 255 o dione 255 » HChiral (2S, 3R)-N, 3-dihydroxy-2- ( { [4- H'XNv (phenylethynyl) phenyl] methyl} amino) butanam 325. 4 H H N, pH 0oh ide 256 H Chlral °H3C OH oyjd) ie Ht N-(3-aminopropyl)-N'- {(1 S, 2R)-2-hydroxy-1- tw [(hydroxyamino) carbonyl] propyl} benzene-l, 4 339 4 rH dicarboxamide 257 NH2 H Chiral HC OH N- { (1S, 2R)-2-hydroxy-1_ HN [(hydroxyamino) carbonyl] propyl}-4- 310. 3 r-o (propanoylamino) benzamide 258 CH3 H OH H, c oH HC-OH OH 1, 1-dimethylethyl 3- [ ( {4- [ ( { (1S, 2R)-2- h hydroxy-1-439. 5 HCHeH [ (hydroxyamino) carbonyl] propyl} amino) carbo 259 o NH nyl] phenyl} carbonyl) amino] propylcarbamate 259 ° H Chiraì , 3C OH HHC ; go N- {(1 S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl}-4'- 407. 4 260 (phenyloxy)-1, 1'-biphenyl-4-carboxamide If 260 oH2C OH 3 N-[(1 S, 2R)-1- 'b ( { [cyano (phenyl) methyl] amino} carbonyl)-2- h ° N hydroxypropyl]-4'-hydroxy-1, 1'-biphenyl-4- Y Yp pY] Y Y P Yl 4- Ho carboxamide 261 U Chiral HC-OH \ pb. oH 4'- { [2- (hydroxyamino)-2-oxoethyl] oxy}-N- K4i o {(lS, 2R)-2-hydroxy-1- OH droxyamino carbonyl]roro1yl'-404. 4 oH [ (Y Y) Y] p pY} HN biphenyl-4-carboxamide 262 o Example Structure _ Name ME+ 0 citrat H JLCHj NsS 4-( { [(1 S, 2R)-1- H ; 4 {[(cyanomethyl) amino] carbonyl}-2-466 5 'o-C (propanoyloxy) propyl] amino} carbonyl)-1, 1'- biphenyl-4-yl propanoate 263 cl, 0 Choral H JCH o'° N"4'- ( { [ (1S, 2R)-1- eHN ; 4 to {[(cyanomethyl) (propanoyl) amino] carbonyl}- H0CH3 2- (propanoyloxy) propyl] amino} carbonyl)-1, 1'- biphenyl-4-yl propanoate 264 CH, H3C.... OH oH3C N- ( ( 1 S, 2R)-1- pN 1 [ (cyanomethyl) amino] r-arbonyll-2- 354. 4 hydroxypropyl)-4'-hydroxy-1, 1'-biphenyl-4- HOw carboxamide 265 0Chiraì HH, (2S, 3S)-2-[(1, 1'-biphenyl-4-ylmethyl) arnino]-301 4 H HN'OH N, 3-dihydroxybutanamide 0 266 OH 0 N- {2-hydroxy-l- [ (hydroxyamiiao) carbonyl]-2- eNH Y OH phenylethyl}-1, 1'-biphenyl-4-carboxamide 3 I 267 H Chiral H oH3CtOH r 0 ! H W N/N sOH (2S, 3R)-2-[(diphenylacetyl) amino]-N, 3-329 4 H O dihydroxybutanamide 268 H Chiraì ruz 3 HN N-{(lS, 2R)-2-hydroxy-1- HN'OH [ (hydroxyamino) carbonyl] propyl}-6- 362. 4 [ (phenylmethyl) thio] pyridine-3-carboxamide 269 H3C OH N H, OH N, 3-dihydroxy-2- ( { [4_ ia (phenyloxy) phenyl] methyl} amino) butanamide 270 270 H Chiral oH, c OH 0 oH N- {(1 S, 2R)-2-hydroxy-1- I "o [ (hydroxyamino) carbonyl] propyl}-2'- 3gg, 3 [ (trifluoromethyl) oxy]-1, 1'-biphenyl-4- F F carboxamide 271 Example Structure Name MH+ H Chiral HO CHjzj N H"'ir N, OH (2R, 3S)-2-[(1, 1-biphenyl-4-ylmethyl) amino] 301 4 H o N, 3-dihydroxybutanamide 272 Chiral HO OH ? T 4- [ ( { (lS, 2R)-2-hydroxy-l- -H TI oH [ (hydroxyamino) carbonyl] propyl} amino) carbo 283. 3 Ho i o nyl] benzoic acid 0 273 H Chiral H, C**fOH CF H 1, 1-dimethylethyl 4- [ (I (lS, 2R)-2-hydroxy-l- H H o oH [ (hydroxyamino) carbonyl] propyl} amino) carbo 339. 4 nyl] benzoate o 274 HO Chiral (4R)-4- { [ (4'-ethyl-1, 1'-biphenyl-4- yl) carbonyl] amino}-5- (hydroxyamino)-5- 371. 4 H, c \/\/o o oH oxopentanoic acid H 275 H/-o"ch ! ra) 4'-ethyl-N- [ (lR)-2- (hydroxyammo)-l- H3cXO O3r4OH (hydroxymethyl)-2-oxoethyl]-1, 1'-biphenyl-4-329. 4 carboxamide 276 oH cnm 4'-ethyl-N- [ (1S)-2- (hydroxyami. no)-1- H c \/\/o o-b°H (hydroxymethyl)-2-oxoethyl]-1, 1'-biphenyl-4- 329. 4 'carboxamide 277 OH Chi; m d HN (2S)-1-[(4'-ethyl-1, 1'-biphenyl-4-yl) carbonyl]-3 4 OH N, 4-dihydroxypyrrolidine-2-carboxamide r-c'o 0 H3c 278 CHChiral 4'-ethyl-N-I (lS)-l- [ (hydroxyaniino) carbonyl] but-3-ynyl}-1, 1'- 337. 4 biphenyl-4-carboxamide 279 NH2 chlrat N- [ (1S)-l- (aminomethyl)-2- (hydroxyamino)-2 H oxoethyl]-4'-ethyl-1, 1'-biphenyl-4- 328. 4 carboxamide 280 Example Structure Name MH+ C CH3 Chiral CL H X Xlr HN N- {(l S)-l-[(hydroxyamino) carbonyl]-2-313 methylpropyl}-1, 1'-biphenyl-4-carboxamide 281 H Chirat HCOH k 'N, N- { (1S, 2R)-2-hydroxy-1- AK, Ja CH3 ° [(hydroxyamino) carbonyl] propyl}-N-methyl-329. 4 cH ° [ (Y Y) Y] P pY} Y 1, 1'-biphenyl-4-carboxamide 282 H Chira) oH3C OHH N°H 4-ethynyl-N- { (1S, 2R)-2-hydroxy-1- 2g3. 3 H H (hydroxyaxnino) carbonyl] propyl} benzamide H 283 H Chiral H3C OH 4- (1, 3-benzodioxol-5-yl)-N- { (1S, 2R)-2- 0 hydroxy-l-359. 3 li [ (hydroxyamino) carbonyl] propyl} benzamide O : c 284 Chi-] N- { (lR, 2S)-2-hydroxy-l- N 0 [ (hydroxyamino) carbonyl] propyl}-4'-propyl- 357. 4 1, 1'-biphenyl-4-carboxan-) ide 285 285 H3C OH N0M, OH 2- ( { [3- (ethyloxy)-1, 1'-biphenyl-4- H3CwOor ° yl] methyl} amino)-N, 3-dihydroxybutanamide 286 Li choral HO OH gS XNOH N- { (lS, 2R)-2-hydroxy-1- H3Csos>j HN H [(hydroxyamino) carbonyl] propyl}-3', 4'- 375. 4 bis (methyloxy)-1, 1'-biphenyl-4-carboxamide n-c'° 287 Chiral oHaC OH 3'-formyl-N- { ( lS, 2R)-2-hydroxy-1- H0 [ (hydroxyamino) carbonyl] propyl}-4'- 373. 4 (methyloxy)-1, 1'-biphenyl-4-carboxamide H, C-° 288 N- { (1S, 2R)-2-hydroxy-1- Ho=°--- °° oH °"°' [ (hydroxyamino) carbonyl] propyl}-4- (4- {4- HQ H [ ( { (IS, 2R)-2-hydroxy-l- 523. 5 [ (hydroxyamino) carbonyl] propyl} amino) carbo 289 nyl] phenyl} buta-l, 3-diynyl) benzamide Example Structure Name MH+ H Chiral OH H N, OH (2S, 3R)-2- (f [4'- (ethyloxy)-1, 1'-biphenyl-4- yl] methyl} amino)-N, 3-dihydroxybutanamide 290 290 H Chita ! H3C OH ? i 3'-chloro-N- { (lS, 2R)-2-hydroxy-l- clo H 0 1 (hydroxyamino) carbonyllpropyll-4'- 379. 8 H. CIO (methyloxy)-1, l'-biphenyl-4-carboxarrfide 291 c oOH Chiral (1R, 2R)-N- { (IS, 2R)-2-hydroxy-1- ' N-OH [ (hydroxyamino) carbonyl] propyl}-2- 279. 3 o phenylcyclopropanecarboxamide 292 oi3Ce, OH Chiraì t-oH N- { (1S, 2R)-2-hydroxy-1- J ! [ (hydroxyamino) carbonyl] propyl}-4-(lH-304. 3 pyrrol-1-yl) benzamide 293 C'OH Chiral YH-OH N- { (lS, 2R)-2-hydroxy-l- , HN Y [(hydroxyamino) carbonyl] propyl}-4-281. 3 [ (Y Y) Y] p PY} H3c propylbenzamide 294 OH3CS OH Chiral v XN-OH N-{(lS, 2R)-2-hydroxy-1- o 1 (hydroxyamino) carbonyl] propyl}-4- 309. 4 H, c pentylbenzamide 295 (y3C OH Chiral gN-OH N- {(1 S, 2R)-2-hydroxy-1- o 1 (hydroxyamino) carbonyl] propyl}-4- 351. 5 octylbenzamide 296 COH Chiral /, $, N-OH (2E)-N- {(1 S, 2R)-2-hydroxy-1- o [ (hydroxyamino) carbonyl] propyl}-3- (4- 279. 3 methylphenyl) prop-2-enamide 297 3 297 COH Chiral gHiiN OH (2E)-N-{(1 S, 2R)-2-hydroxy-1- s [(hydroxyamino) carbonyl] propyl}-3- [4- 333. 3 F (trifluoromethyl) phenyllprop-2-e-namide F F 298 Example Structure Name MH+ i3c o cntm N-OH (2E)-3- (1, 1'-biphenyl-4-yl)-N- { (1S, 2R)-2- 0 drox-1- y y 341. 4 [ (hydroxyamino) carbonyl] propyl} prop-2- enamide 299 cnim <34t3CtOH (2S, 3R)-2- [ (1, 1'-biphenyl-4-ylacetyl) amino]- Hw N, 3-dihydroxybutanamide H 0 300 oH3C~, Chira ! HN4N-OH (2S, 3R)-2- { [ (2S)-2-amino-3- (1, 1'-biphenyl-4- /HN"IOI yl) propanoyl] amino}-N, 3- 358. 4 dihydroxybutanamide 301 oi3Cs, OH Chiral wNi N-OH (2S, 3R)-2- { [ (2R)-2-amino-3- (l, l'-biphenyl-4- I/HZN"O yl) propanoyl] amino}-N, 3- 358. 4 dihydroxybutanamide 302 Lq H2 C OH Chlral NN-OH ( S)-3-amino-N- { ( S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl}-5- 310. 4 phenylpentanamide 303 C OH Chiral vNiN-OH N-{(1S, 2R)-2-hydroxy-1- b " [ (hydroxyamino) carbonyl] propyl}-4-344. 4 Y] p PY} [ (phenylamino) methyl] benzamide 304 dC OH Chiral N-f (lS, 2R)-2-hydroxy-l- RHJYH>N-OH [(hydroxyamino) carbonyl] propyl}-4-358. 4 N i rI0 N O {[(phenylmethyl) amino] methyl} benzamide 305 H, ; HC OH Chimi 4'-ethyl-N-f (lS, 2R)-2-hydroxy-l- [ (f (lS, 2R)-2 x' -b-o"hydroxy-1_ H3C aC Cx [(hydroxyamino) carbonyl] propyl} amino) carbo 444. 5 nyl] propyl}-1, 1'-biphenyl-4-carboxamide 306 ) hC-OH Chiral (2S, 3R)-2- [ (1, 1'-biphenyl-4-ylacetyl) amino]-3- WSH4NHW OH hydroxy-N- {(1 S, 2R)-2-hydroxy-1-430. 5 ° [(hydroxyamino) carbonyl] propyl} butanamide 307 Example Structure Name MH+ 13C OH Chiral NrM-oH 4- (4-chlorophenyl)-N- { (1S, 2R)-2-hydroxy-l- H 0 [ (hydroxyamino) carbonyl] propyl} cyclohexane 355. 8 carboxamide ce 308 H Chiral õi3Cs, OH Chiraì 4, NX N-OH N- {(1 S, 2R)-2-hydroxy-1- N_N4 ; H o [(hydroxyamino) carbonyl] propyl}-4-(lH-305. 3 [ (Y Y) Y] p pY} ( Wi pyrazol-l-yl) benzamide 309 C OH Chiral 4, N@N-OH N-{(lS, 2R)-2-hydroxy-1- H 10l [ (hydroxyamino) carbonyl] propyl}-4- 324. 3 ° i morpholin-4-ylbenzamide 0 310 oi3Cs, OH Chiral N-OH N-f (I S, 2R)-2-hydroxy-l- /eJ H o [(hydroxyamino) carbonyl] propyl}-4- (1, 2, 3- 323. 3 s N thiadiazol-4-yl) benzamide 'N 311 C'OH Chiral N- { (IS, 2R)-2-hydroxy-l- 3 sNo ; HHNw [(hydroxyamino) carbonyl] propyl}-4-[(4-351. 4 methylpiperazin-1-yl) methyl] benzamide 312 dC OH Chiral N-I (lS, 2R)-2-hydroxy-l- N. yNY'''OH [ (hydroxyammo) ca]-bonyl] propyl}-4- (lH- 319. 3 H 0 iniidazol-1-yhnethyl) benzamide 313 oH3C OH Chireil.. _ 61,, OH Chiral (2S, 4S)-N-{(lS, 2R)-2-hydroxy-1- N ; [ (hydroxyaniino) carbonyl] propyl}-4- 308. 3 ° phenylpyrrolidine-2-carboxamide 314 H. C OH Chiral t t NH 4'-bromo-N-{(lS, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl}-l, l'-394. 2 biphenyl-4-carboxamide 315 H3C OH Chiral R X, NH 4'-bromo-N- {(1 S, 2R)-2-hydroxy-1- -OH [ (hydroxyamino) carbonyl] propyl}-l, l'-394. 2 biphenyl-4-carboxamide 316 Exam le Structure Name . H3C OH Chiral t X NH 4'-bromo-N-{(lS, 2R)-2-hydroxy-1- ° oH [ (hydroxyamino) carbonyl] propyl}-1, 1'- 394. 2 biphenyl-4-carboxamide 317 0 alral (2R)-2- { [ (4'-ethyl-1, 1'-biphenyl-4- yl) carbonyl] amino}-N-1-- 370. 4 H, c //o 0 oH hydroxypentanediamide 318 , OH Chiral (2S, 3S)-1- [ (4'-ethyl-1, 1'-biphenyl-4- oH yl) carbonyl]-3-hydroxypyrrolidine-2- 340. 4 HC //O O carboxylic acid 319 OH Chiml (2S, 3S)-N-[(l, l-dimethylethyl) oxy]-1-[(4'- mN+NHi o4Fciz ethyl-l, 1'-biphenyl-4-yl) carbonyl]-3-41 1. 5 ''hydroxypyrrolidine-2-carboxamide 320 OH oH °nim (2S, 3S)-1- [ (4'-ethyl-1, 1'-biphenyl-4- N yl) carbonyl]-N, 3-dihydroxypyrrolidine-2- 355. 4 H3 carboxamide 321 H Cam HC OH < XN N-{(lS, 2R)-2-hydroxy-1- . t [(hydroxyamino) carbonyl] propyl}-4- [ (4- 384. 4 nitrophenyl) ethynyl] benzamide 322 ° H Chiral 03-OU 0 T n N- { (lS, 2R)-2-hydroxy-1- l [(hydroxyamino) carbonyl] propyl}-4-{[4-(lH-404. 4 CNti pyrrol-1-yl) phenyl] ethynyl} benzamide 323 H Chlral °H3C OH gNOH N- {(l S, 2R)-2-hydroxy-1- ° [ (hydroxyamino) carbonyl] propyl}-4'-nitro-1, 1' 360. 3 ON biphenyl-4-carboxarrAde 324 0_ H3C Li OH Chiral 3 XN (2S, 3R)-N, 3-dihydroxy-2-( { [4-(methyloxy)-3 6C-H0 propyl-1, I'-biphenyl-4-373. 5 H3C oXi yl] methyl} amino) butanamide 0 325 Example Structure Name MH+ H Chiral HC OH o OH 4'-cyano-N- ( (I S, 2R)-2-hydroxy- 1- > H H o [(hydroxyamino) carbonyl] propyl}-l, l'-340 3 biphenyl-4-carboxamide N 326 Chiral W Ch ! HC. H, C OHH 7N. 't (2S, 3R)-2-( { [4'-(ethyloxy)-4-(methyloxy)-1, 1'- biphenyl-3-yl] methyl} amino)-N, 3- 375. 4 dihydroxybutanamide 327 cl, C H °H Chiral HC-OH ° g NH 2', 5'-difluoro-N- {(1 S, 2R)-2-hydroxy-1- vH o [(hydroxyamino) carbonyl] propyl}-l, l'-351. 3 biphenyl-4-carboxamide 328 F 0 Ch) rat N- [ (1S)-1- [ (acetylamino) methyl]-2- (hydroxyamino)-2-oxoethyl]-4'-ethyl-1, 1'- 370. 4 H3C/o ot oH biphenyl-4-carboxamide 329 NHzchm N- N-( lS)-4-amino-1- X FFt [(hydroxyamino) carbonyl] butyl}-4'-ethyl-1, 1'-356. 4 c oo'oH Fi3C o o OH biphenyl-4-carboxamide 330 IN i 4'-ethyl-N-[(1 S)-2-(hydroxyamino)-1-(lH- N 4 N imidazol-5-ylmethyl)-2-oxo ethyl]-1, 1-379. 4 H3CHo or òH biphenyl-4-carboxanzide 331 OH Chiral N-OH (2S, 3R)-2- { [1- (l, 1'-biphenyl-4- ° yl) ethyl] amino}-N, 3-dihydroxybutanamide 315. 4 332 332 H3C H3C OH Chiral s iN OH (2S, 3R)-2- { [1- (1, 1'-biphenyl-4- ° yl) propyl] amino}-N, 3-dihydroxybutanamide 333 CNCoOH Chinl J'N N-OH Hl ; o (2S, 3R)-2- { [1- (4'-bromo-1, 1'-biphenyl-4- ° yl) ethyl] amino}-N, 3-dihydroxybutanamide B 334 Example Structure Name MH+ c1A3 Y 1 I M HN (2S, 3R)-N, 3-dihydroxy-2- { [1-(4'-methyl-1, 1'-329 4 biphenyl-4-yl) ethyl] amino} butanamide HzN HC 335 HN Chirs ! H2N Chiral 0 N-r-0"N- [ (lS)-l- (aminomethyl)-2- (hydroxyaniino)-2- ° oxoethyl]-1, 1'-biphenyl-4-carboxamide i 336 H, N Chiral ? 1 H " N-OH N- [ (lS)-l- (aminometliyl)-2- (hydroxyamino)-2 289, 3 CN o oxoethyl]-4-(lH-pyrrol-l-yl) benzarnide G 337 H2N Chiral HN Ch ! ta ,, H-OH N- [ (lS)-I- (aminomethyl)-2- (hydroxyamino)-2. H H 0 oxoethyl]-4- (4- 340. 8 chlorophenyl) cyclohexanecarboxamide ce 338 °HZtN Chiral S) >4v N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 294 4 oxoethyl]-4-pentylbenzamide HzN 339 H aN Chiral Pi 1 irM"T' (2E)-N- [ (lS)-l- (ammomethyl)-2- p (hydroxyamino)-2-oxoethyl]-3-(1, 1'-biphenyl-326. 4 4-yl) prop-2-enamide 340 H ;, N Chira) y-N-)-yM-OH (2S)-3-an-iino-2-1 [ (4'-ethyl-1, 1'-biphenyl-4- yl) methyl] amino}-N-hydroxypropanamide c I i 341 H, N Chiral HN-OH (2S)-3-amino-2- [ (1, 1'-biphenyl-4-' ° ylmethyl) amino]-N-hydroxypropanamide 342 H, N Chio ! H N Chiral H-OH (2S)-3-anlino-2-f [1- (4'-bromo- 1, I'-biphenyl-4-379. 3 yl) ethyl] amino}-N-hydroxypropanamide Br 343 Example Structure Name MH+ CH N Chiral N''N-°H (2S)-3-amino-N-hydroxy-2- { [1- (4'-methyl-1, 1' ° biphenyl-4-yl) ethyl] amino} propanamide H3C-oN KjC 344 o"° oH °hm 4'-ethyl-N- [ (1S)-2- ( { (1S, 2R)-2-hydroxy-1- } X1 (NH-OH [(hydroxyamino) carbonyl] propyl} amino)-l-430 5 ", ° i ; -p ° (hydroxymethyl)-2-oxoethyl]-1, 1'-biphenyl-4- carboxamide 345 HO '4'-ethyl-N- { (lS)-2- ( { (lS, 2R)-2-hydroxy-l- " Y°M- [ (hydroxyammo) carbonyl] propyl} amino)-l- [ (4- H c HH>H o hydroxyphenyl) methyl]-2-oxoethyl}-1, 1- biphenyl-4-carboxamide 346 (2S)-2- { [ (4'-ethyl-1, 1'-biphenyl-4- H, N ° Chiral H3C OH yl) carbonyl] amino}-N~l~-{(lS, 2R)-2- hydroxy-l-471. 5 ° [ (hydroxyammo) carbonyl] propyl} pentanediam 347 ide Ho-0 chl. 1 (4S)-4-1 [ (4'-etliyl-1, 1'-biphenyl-4- I HC OH °t1 NX NH-oH yl) carbonyl] amino}-5-({(lS, 2R)-2-hydroxy-1-472 5 H3C_<Ht O [(hydroxyamino) carbonyl] propyl} arnino)-5- oxopentanoic acid 348 HO 0H H Chimi (3S)-3- { [ (4'-ethyl-1, 1'-biphenyl-4- oH yl) ca !-bonyl] ammo}-4- ( { (lS, 2R)-2-hydroxy-l- gg g FC SLHW O [(hydroxyamino) carbonyl] propyl} arnino)-4- oxobutanoic acid 349 ( (3S)-2- (1, 1'-biphenyl-4-ylacetyl)-N- { ( S, 2R)- N"3° 2-hydroxy-l- o"488. 6 1 (hydroxyamino) carbonyl] propyl}-1, 2, 3, 4- 0 OH tetrahydroisoquinoline-3-carboxamide q 350 H3C OH Chtel 4'-ethyl-N- [ (lS)-2- ( { (1S, 2R)-2-hydroxy-1- < 4,, HXI., N-oH [(hydroxyamino) carbonyl] propylamino)-l-414 5 "3° ; i-b 1°r b ° methyl-2-oxoethyl]-1, 1'-biphenyl-4- carboxamide 351 H=N"'°x °"-°"'' (2S, 3R)-2- ( { (2S)-3-amino-2- [ (1, 1'-biphenyl-4- ylacetyl) amino] propanoyllamino)-N, 3- 415. 5 dihydroxybutanamide 352 Example Structure Name MH+ -2- [ (1, l'-biphenyl-4-ylacetyl) amino]-N- o Y b-oH { (1S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} pent-4- ynamide 353 o Chiial I w \ I 3c oH (2S, 3R)-2-{[(2S)-2-arnino-2-(1, 1'-biphenyl-4-344 4 vHX yl) ethanoyl] amino}-N, 3-dihydroxybutanamide Han H ; 0 354 Chiral Ch) na ! C OH (2S, 3R)-2-{[(2R)-2-amino-2-(1, 1'-biphenyl-4-344 4 Wus yl) ethanoyl] amino}-N, 3-dihydroxybutanamide H2N : H O 355 NHZ H, C NH2 N- (3-arriinopropyl)-4'-etllyl-N- [2- w N oH (hydroxyamino)-2-oxoethyl]-1, 1'-biphenyl-4- 356. 4 N-AN'OH carboxamide 0 356 iN H3cA 4, N N-(2-cyanoethyl)-4'-ethyl-N-[2- 0 >1 > (hydroxyamino)-2-oxoethyl]-1, 1'-biphenyl-4-352. 4 N N OH carboxamide 357 o U H, H NJt CH3 N-[2-(acetylammo) ethyl]-4'-ethyl-N-[2- < 0 ° (hydroxyarnino)-2-oxoethy. l]-1, 1'-biphenyl-4-384. 4 carboxamide 0 358 H3CA CH 4'-ethyl-N- [2- (hydroxyamino)-2-oxoethyl]-N- 337. 4 N OH prop-2-ynyl-1, 1'-biphenyl-4-carboxamide O H 359 8'3C OH Chial b-OH 4-cyano-N- { ( S, 2R)-2-hydroxy-1-264. 3 nosh [(hydroxyarn ino) carbonyl] propyl} benzamide N N 360 HN Chiral O 1 0 N-OH N- [ (IS)-l- (aniinomethyl)-2- (hydroxyaniino)-2. 249. 2 /S o oxoethyl]-4-cyanobenzamide N 361 Example Structure Name MH+ NH 1, 1-dimethylethyl (2S)-2- { [ (4- ° . b, ethynylphenyl) carbonyl] amino}-3- 348. 4 (hydroxyamino)-3-oxopropylcarbamate 362 H CH Chiral F6cteH3 oo 1, 1-dimethylethyl (2S)-3-(hydroxyamino)-3- N"oxo-2- [ ( {4- [ (E)-2- b. oH p Y Y] p Y} Y)] p pY hen lethen 1 hen 1 meth 1 amino ro lcar 412. 5 bamate 363 joo H3C, OH Chiral N . OH N- { (lR, 2S)-2-hydroxy-l- FraKW H o [(hydroxyamino) carbonyl] propyl}-3'-383. 3 s (trifluoromethyl)-1, 1'-biphenyl-4-carboxamide 364 H Chiral H3C OH ni (2S, 3R)-2- [ (1, 1'-biphenyl-4-yhnethyl) amino]-3 H0 hydroxybutanoic acid 286. 3 365 Han Chiral o ç NH-OH N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 324 4 o oxoethyl]-4-(phenylethynyl) benzamide 366 366 H, It Chi. 1 9Nri 1, 1-dimethylethyl (2S)-3- (hydroxyamino)-3- nu rX I NHooH (phenylethynyl) phenyl] carbonyl} amino) propyl carbamate 367 Nez Chiral 0 ; H HoH N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 H oxoethyl]-4-ethynylbenzamide H H 368 Nez Chiral 0 H w N'oH N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2 i oxoethyl]-4-ethynylbenzamide 248. 3 H 369 369 HC H OH Chiral Y, N- { (lS, 2R)-2-hydroxy-l- sS [(hydroxyamino) carbonyl] propyl} 4 {[4 369. 4 (methyloxy) phenyl] ethynyl} benzamide 370 Example Structure Name MH+ Nu2 Chiral f hioH (2S)-3-amino-N-hydroxy-2-[({4-[(E)-2- XH phenylethenyl] phenyl} methyl) amino] propana 312. 4 t mide mide 371 H, C-OH Chiral l, l-dimethylethyl 2-{4-[({(lS, 2R)-2-hydroxy- b. °" 1_ HCX'X wHi [(hydroxyamino) carbony, l] propyl} ammo) carbo 458. 5 nyl]-1, 1'-biphenyl-4-yl} ethylcarbamate 372 '"LoH (2S, 3R)-N, 3-dihydroxy-2-[({4'-[(2-pyrrolidm- HN ; 5jo 1-ylethyl) oxy]-1, 1'-biphenyl-4-414. 5 yl} methyl) amino] butanamide 373, 1, 1-dimethylethyl (1S)-4- ( { [ (1, 1- H, ° H °H hlrel /JXNOH dimethylethyl) oxy] carbonyl} amino)-1-({[4- H, (f4- [ (f (lS, 2R)-2-hydroxy-l- 668. 8 H,"CH, 6c 0 (hydroxyamino) carbonyl] propyl} amino) carbo 668. 8 374 nyllphenyl) ethynyl) phenyl] amino} carbonyl) b 374 utylcarbamate H, C OH Chi2 4- (4-chlorophenyl)-N- [ (1S)-2- ( { (1S, 2R)-2- N-OH hydroxy-l- CI ° [ (hydroxyammo) carbonyl] propyl} ammo)-l-426. 9 375 methyl-2-oxoethyl] cyclohexanecarboxamide 375 O gN-4'-ethyl-N-[2-( {(1 S, 2R)-2-hydroxy-1- -Y [ (hydroxyamino) carbonyl] propyl} amino)-2- 400. 4 oxoethyl]-1, 1'-biphenyl-4-carboxamide 376 Hc OH Chiral 4'-ethyl-N- [3- (I (IS, 2R)-2-hydroxy-l- bp-b°" [ (hydroxyamino) carbonyl] propyl} amino)-3- 414. 5 ° ° oxopropyl]-1, l'-biphenyl-4-carboxamide 377 H, c c. . 4'-ethy !-N- [4- ( { (lS, 2R)-2-hydroxy-l- 0 0 [ (hYdrOxYamino) carbonyllpropyl) amino)-4- 428. 5 oxobutyl]-1, 1'-biphenyl-4-carboxamide 378 HzN Chlral N- ( (1S)-2- { [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2-oxoetliyl] aminol-l-methyl- 2-oxoethyl)-4'-ethyl-1, 1'-biphenyl-4- carboxamide 379 Example Structure Name ME+ HzN Chhsl N- (2- { [ (1S)-1- (aminomethyl)-2- ° . b-oH (hydroxyamino)-2-oxoethyl] amino}-2- H, ° - ° oxoethyl)-4'-ethyl-1, 1'-biphenyl-4- carboxamide 380 N- (3- { [ (lS)-l- (ammomethyl)-2- ° HzN Chfral p pNb-oH (hydroxyamino)-2-oxoethyl] amino}-3- ° oxopropyl)-4-ethyl-1, 1-biphenyl-4- carboxamide 381 N- (4- { [ (ls)-1- (aminomethyl)-2- qu XN (hydroxyamino)-2-oxoethyl] ammo}-4-41 ° oxobutyl)-4'-ethyl-1, 1'-biphenyl-4- carboxamide 382 H3 f CH3 4'-ethyl-N-[l-[(hydroxyamino) carbonyl]-2- (methyloxy) propyl]-1, 1'-biphenyl-4- 357. 4 H C 0 OH carboxamide 383 H, CI-hChiral 4'-ethyl-N- [ (1S, 2R)-1- Hto [(hydroxyamino) carbonyl]-2- H3c 0 OH (methYloxy) propyll-1, 1'-biphenyl-4- H, c o 0 oH (y 3') p py] p Y carboxamide 384 PH3 H N- [1- [ (dimethylamino) methyl]-2- (hydroxyamino)-2-oxoethyl]-4-ethyl-1, 1'- 356. 4 Ha 0 OH biphenyl-4-carboxamide 385 385 N- { (1S)-3-cyano-1- 1 (hYdroxYanlino) carbonyllpropyl}-4'-ethyl-1, 1' 352. 4 H3C O O OH biphenyl-4-carboxamide 386 386 N- { ( 1 S)-5-amino-1- [ (hYdroxYanlino) carbonyllpentyl)-4'-ethyl-l, l 370. 5 biphenyl-4-carboxamide 387 FiH2Chiial , N-{(lS)-3-ammo-1- [ (hydroxyamino) carbonyl] propyl}-4'-ethyl-1, 1' 342. 4 \/\/ a biphenyl-4-carboxamide 388 xample Structure Name MH+ H , < 6Ms-OH 4'-ethyl-N-hydroxy-1, 1'-biphenyl-4-242. 3 242. 3 H3 carboxamide 389 CL 13C C OH 0i3Ct 4'-ethyl-N- {2-hydroxy-1- , ii OH [(hydroxyamino) carbonyl]-2-methylpropyl}-357. 4 390 H3cs 1, 1'-biphenyl-4-carboxamide 3 390 o,-1 ohiri N- [ (2S)-2-1 [ (4'-ethyl-1, 1'-biphenyl-4- 0 H-OH yl) carbonyl] amino}-3- (hydroxyamino)-3- 441. 5 H, c/ o oxopropyl] morpholine-4-carboxamide 391 O Chlral NH N- [ (lS)-l- { [ (ammocarbonyl) ammo] methyl}-2. 0 my H-OH (hydroxyaniino)-2-oxoethyl]-4-ethyl-1, 1'- 371. 4 H, C 0 biphenyl-4-carboxamide 392 HN Chiral o H ( { [animo (in] mo) methyl] amino} methyl)-2-. 0 _<eNiw (hydroxyamino)-2-oxoethyl]-4'-ethyl-1, 1'- biphenyl-4-carboxamide 393 O Chiral bl N- [ (2S)-2-amino-3- (hydroxyamino)-3- XHL2N) N-OH oxopropyl]-4-ethyl-1, 1-biphenyl-4-328. 4 H, c no carboxamide 394 H N CN °H 1- [ (4'-ethyl-1, 1'-biphenyl-4-yl) carbonyl]-N- 395 H3C vO hydroxypiperazine-2-carboxamide H3c/ O 3 5 O H Chiral N b-oH N- [ (2S)-2-amino-3- (hydroxyamino)-3- N o oxopropyl]-4- (phenylethynyl) benzamide 396 t N N-OH N-hydroxy-1- { [4- o hen leth 1 hen 1 carbon 1 i erazine-2-350. 4 o (P Y YnY) p Y] Y} P P 397 carboxamide 397 Example Structure Name MH+ H Hc ON 4 XNvOH N-{(lS, 2R)-2-hydroxy-1- " [ (hydroxyamino) carbonyl] propyl}-4- [ (4- 409. 5 H ° pentylphenyl) ethynyl] benzamide 398 H, H OH Chiral . YoH N- { (lS, 2R)-2-hydroxy-l- H o [ (hydroxyamino) carbonyl] propyl}-4- { [3- 369. 4 CH3 i (methyloxy) phenyl] ethynyl} benzamide 399 C H oH cnirai v T NOH 4-[(3-fluoro-4-methylphenyl) ethynyl]-N- AS {(lS, 2R)-2-hydroxy-1-371. 4 [ (hydroxyamino) carbonyl] propyl} benzamide 40 ° H3C 400 HaCHOH Chiral O e XNsOH 4-[(2, 4-difluorophenyl) ethynyl]-N- { (IS, 2R)-2- F'9 H O hydroxy-l-375. 3 [ (hydroxyamino) carbonyl] propyl} benzamide i 401 cCH3 H3C NH , i ovc methyl (2E)-3-(ethylamino)-2-({[4- (phenylethynyl) phenyl] carbonyl} amino) but-2- 363. 4 v enoate I 402 UN chiez ° 1, 1-dimethylethyl 4- { [ (2S)-3- (hydroxyamino)- ? jet 3-oxo-2- (f [4- H, I ; m'OH (phenylethynyl) phenyl] carbonyl) anlino) propyl 509. 6 ] amino}-4-oxobutylcarbamate CH3 Cl H3C OH X, Hj N-(l-(N-hydroxyvarbamoyl)-2-hydroxy-3- N'jYH'OH methylbutyl) [4- (4- 371. 4 ethylphenyl) phenyl] carboxamide c I 404 p H Chirdl N- ( (1R, 2R)-1- { [ (aminocarbonyl) (hydroxy) amino] methyl}-2-372 4 QH NHZ hydroxypropyl)-4'-ethyl-1, 1'-biphenyl-4- carboxamide 405 0OH Chiral J'-M-'cH, 4'-ethyl-N- ( (lR, 2R)-l- -kH f [forinyl (hydroxy) amino] methyl}-2-357. 4 H3cJU OH hydroxypropyl)-1, 1'-biphenyl-4-carboxamide 406 Example Structure Name MH+ HCHOH Chiral O YNToH N- { (lS, 2R)-2-hydroxy-l- 0 [ (hydroxyaniino) carbonyl] propyl}-4- { [4- 407. 4 FxU (trifluoromethyl) phenyl] ethynyl} benzamide 407 F F rniai 1, 1-dimethylethyl 2- { [(2S)-3-(hydroxyamino)- Nh 3oxo2 ( { [4 ieHX OH (phenylethynyl) phenyl] carbonyl} amino) propyl v] amino}-2-oxoethylcarbamate 408 t i XHz Chir31 zoo o p N- [ (1S)-1= { [ (aminoacetyl) amino] methyl}-2- o" (hydroxyamino)-2-oxoethyl]-4-381. 4 (phenylethynyl) benzamide 409 iS MH Oq/Hi N- [ (1S)-1- { [ (4-aminobutanoyl) amino] methyl} 2- (hydroxyamino)-2-oxoethyl]-4- 409. 5 (phenylethynyl) benzamide 410 410' H3C H OH Chiral ii A iN N-{(lS, 2R)-2-hydroxy-1- "1r [ (hydroxyamino) carbonyl] propyl}-4-pent-1- 305. 3 i ynylbenzarnide HC 411 pHech, m H3C H OJGCH ° t rHsa N- {(1 S, 2R)-2-[(1, l-dimethylethyl) oxy]-l- ieHt [(hydroxyamino) carbonyl] propyl}-4'-propyl- 413. 5 < 1, 1'-biphenyl-4-carboxamide HzN 412 ", °. °" H l, l-dimethylethyl (lS)-4- ( { [ (l, l- ''b'°"dimeth leth 1 ox carbon 1 amino-1 2-4' Y SHw [({(lS, 2R)-2-hydroxy-1- h droxyamino) carbonyl] propyl} amino carbo 672. 8 ocH, nyl]-l, l'-biphenyl-4- 413 eth 1 ami. no carbon 1 bu lcarbamate H3C H OH Chbal 4'- (2-aminoethyl)-N- { (1S, 2R)-2-hydroxy-1- NH0 [ (hydroxyamino) carbonyl] propyll-1, 1'- 358. 4 biphenyl-4-carboxamide HzN 414 H, C H OH Chiml OH 4'- (2- { [ (2S)-2, 5- diaminopentanoyl] amino} ethyl)-N- { (1S, 2R)-2 - 472. 6 ", p hydroxy-1- [ (hydroxyamino) carbonyl] propyl}- 415 nez 1, 1'-biphenyl-4-carboxamide 415 ExampleStructureNameMH+ cniri H3C-OH O H = N, OH 4- (cyclohex-l-en-1-ylethynyl)-N- { (lS, 2R)-2- NH H o hydroxy-l-343. 4 [ (hydroxyamino) carbonyl] propyl} benzamide 416 H3C t OH Chiral O 'oH 4- (3, 3-dimethylbut-1-ynyl)-N- ( (1S, 2R)-2- won H H 0 hydroxy-1-319. 4 3c< [(hydroxyamino) carbonyl] propyl} benzamide c cH, 417 i °hm N- { ( S)-1- f [ (aminoacetyl) amino] methyl}-2- [ (2-f [ (2S)-3- (hydroxyamino)-3-oxo-2- (1 [4- O fN"H Otl (phenylethynyl) phenyl] carbonyl} amino) propyl 728. 8 ° d. ° , (p Y YnY) p Y] Y}) P pY a ° °"] amino}-2-oxoethyl) amino]-2-oxoethyl}-4- 418 (phenylethynyl) benzamide H, C 8 OH Chir-31 oH 4- [ (4- { [ (2S)-2, 5- diaminopentanoyl] amino} phenyl) ethynyl]-N- H/N {(l S>2R)-2-hydroxy-l-468. 5 [ (hydroxyamino) carbonyl] propyl} benzamide 419 NH- HCH, O < OH 4'-(2-amimoethyl)-N-{(lE)-l- 0 [ (hydroxyamino) carbonyl] prop-l-enyl}-1, 1'- 340. 4 H2Nv biphenyl-4-carboxarnide 420 H3C H OH Chiral Jk % N 2', 4'-difluoro-N- {(1 S, 2R)-2-hydroxy-1- , L, H H 8 OH [(hydroxyam-ino) carbonyl] propyl}-l, l'-351. 3 biphenyl-4-carboxamide 421 421 F HOCH, O H N- [ (lE)-1-formylprop-1-enyl]-4'-propyl-1, 1'- biphenyl-4-carboxamide 308. 4 422 422 N-O N-OH N-hydroxy-4- (pyridin-3-ylethynyl) benzamide 239. 2 H 423 O C H oH Chlral 4- (3-hydroxy-3, 5-dimethylhex-1-ynyl)-N- H SAi O {(lS, 2R)-2-hydroxy-1-363. 4 [ (hydroxyamino) carbonyl] propyl} benzamide con 424 Example structure ~ Name MH+ Chiral 4'-ethyl-N- { (1R, 2R)-2-hydroxy-1- o" [ (hydroxyamino) methyl] propyl}-1, 1'-biphenyl- 329. 4 nf Jf J 4-carboxamide 425- 425 425 iX 4'-ethyl-N-{(lR, 2R)-l- 'o [ (hydroxyamino) methyl]-2- HN ÒH [(phenylmethyl) oxy] propyl}-l, l'-biphenyl-4- [ (p Y Y) Y] p pY} p Y 426 H3Co carboxamide 426 13C O/OChfral 4'-ethyl-N- [ (5R, 6R)-3-hydroxy-6-methyl-2- H, C H OH oxo-1, 3-oxazinan-5-yl]-l, I'-biphenyl-4-355. 4 carboxamide 427 -N- ( (1R2R)-1- { [ ( { [2_ (4NH) t, NAH~N-CH, (dimethylamino) ethyl] amino} carbonyl) (hydro Fi xy) amino] methyl}-2-hydroxypropyl)-4'-ethyl- 1, 1'-biphenyl-4-carboxamide 428 N- ( (1R2R)-1- { [ { [ (2_ - -" ", cyanoethyl) amino] carbonyl} (hydroxy) aniffiol Cm OH methyl}-2-hydroxypropyl)-4'-ethyl-1, 1'- biphenyl-4-carboxamide 429 4'-ethyl-N- ( (lR, 2R)-2-hydroxy-l- HH { [hydroxy ( { [3- (2-oxopyn-olidin-l- g ", CJr OH sw yl) propyl] amino} carbonyl) amino] methyl} prop yl)-1, 1'-biphenyl-4-carboxamide 430 , (1R, 2R)-3- [( { [2- °>N~NsCH (dimethylamino) ethyl] amino} carbonyl) (hydro xy) amino]-2- { [ (4'-ethyl-1, 1'-biphenyl-4- 557. 7 Csv OH yl) carbonyl] amino}-l-methylpropyl 2- 431 (dimethylamino) ethylcarbamate Chiral (1R, 2R)-3- [ { [ (2- H, H cyanoethyl) amino] carbonyl} (hydroxy) amino]- "2- { [ (4'-ethyl-1, 1'-biphenyl-4- 521. 6 HcsJV yl) carbonyl] amino}-l-methylpropyl 2- 432 cyanoethylcarbamate H CH3 n° X H ef H Y N-{(lE)-l-[(E)-(hydroxyimino) methyl] prop-l- °H enyl}-4'-propyl-1, 1'-biphenyl-4-carboxamide 323. 4 H3Cw 433 Example structure Name MH+ H3CHOH Chiral O H'oH N- { (1S, 2R)-2-hydroxy-1- H0 [ (hydroxyamino) carbonyllpropyl)-4- (pyridin- 340. 3 3-ylethynyl) benzamide 434 H CHOH Chiral O m'OH N-f (I S, 2R)-2-hydroxy-l- J''o [ (hydroxyammo) carbonyl] propyl}-4- [3- 306. 3 (r(methylamino) prop-1-ynyl] benzamide NH 435 , CH3Chirai N N- [ (lS)-l- [ (dimethylamino) methyl]-2- ms Hx 3 (hydroxyamino)-2-oxoethyl]-4'-eíhyl-1, 1'-356. 4 3 biphenyl-4-carboxamide 436 3 f OH-N-[l-(N-hydroxyzarbamoylmethyl) (lR, 2R)-2- <Hiso hydroxypropyl] [4- (4- 357. 4 H ethylphenyl) phenyl] carboxamide 437 cH3chm N- [ (lS)-1- [ (diethylamino) methyl]-2- H3c ROH (hYdroxyamino)-2-oxoethyl]-4-ethyl-1, 11- 384. 5 H3c o o OH biphenyl-4-carboxarnide 438 H, CHOH Chiral XNsOH 4-[(3-aminophenyl) ethynyl]-N-{(lS, 2R)-2- H JU H O hydroxy-l-354. 4 1 (hYdroxYamino) carbonyllpropyllbenzamide 439 C CH °H Chlral 0 4-[3-(dimethylamino) prop-1-ynyl]-N- {(1 S, 2R) 2-hydroxy-l-320. 4 H CN/ [(hydroxyamino) carbonyl] propyl} benzamide HC 440 H, CIOH Chlral b, °" 4- [3- (dimethylamino) prop-1-ynyl]-N- { (1S, 2R) 2-hydroxy-I-320. 4 H C-N/ [(hydroxyamino) carbonyl] propyl} benzamide HC 441 H, C-OH M, OH 4- (14- [ (atninoacetyl) amino] phenyl} ethynyl)-N v {(l S, 2R)-2-hydroxy-1-4 11. 4 H2NsANJC [(hydroxyamino) carbonyl] propyl} benzamide 442 Example structure | Name MH+ H3C H OH Chiral O Jt XN 3'-fluoro-N-{(lS, 2R)-2-hydroxy-1- F H 0 [ (hydroxyamino) carbonyl] propyl}-4'-methyl- 347. 4 I 1, 1'-biphenyl-4-carboxamide H3C 443 H3C Cl3 Chiral - : fH N N- [ (1S)-1-formyl-2-methylpropyl]-1, 1'- H o '1 i i. . o. 4 biphenyl-4-carboxamide 444 444 H3C CH3Chiral 0 t N N- { (IS)-l- [ (E)- (hydroxyimino) methyl]-2- 297. 4 methylpropyl}-1, 1'-biphenyl-4-carboxamide i 445 CH O H I ''N J N_ ( (lE) _1_ { (E) _ w J NH2 [ (aminocarbonyl) hydrazono] methyl} prop-l- 365. 4 'enyl)-4'-propyl-1, 1'-biphenyl-4-carboxamide 446 hic 0 Chiral N3C--OH O H ,, jv XF OH 4-[(4-ammophenyl) ethynyl]-N- {(1 S, 2R)-2- hydroxy-1-354. 4 h drox Ja (ydroxyamino) carbonyl] propyl} benzamide 447 447 H Chtral H3C-OH NHOH 4- { [3- (aminomethyl) phenyl] ethynyl}-N- JC'"° { (lS, 2R)-2-hydroxy-l- 368. 4 [ (hydroxyamino) carbonyl] propyl} benzamide 448 o C Fi CN Chiral N_ (2-aminoethyl)-3- ( {4- [ ( { (1S, 2R)-2-hydroxy 0 M, OH I-425. 5 [ (hydroxyamino) carbonyl] propyl} amino) carbo 449 nyl] phenyl} ethynyl) benzamide 449 H 3CCH3Chiral vNX N-((lS)-l-{(E)- I H" /N. NH [ (ammocarbonyl) liydrazono] methyl}-2- 339. 4 methylpropyl)-1, 1'-biphenyl-4-carboxamide 'HN 0 450 H30 UOH Chl. 1 N- { (lS, 2R)-2-hydroxy-l- N HJ ° [(hydroxyamino) carbonyl] propyl}-4-{[3-410. 4 r s H, Cf' (propanoylamino) phenyl] ethynyl} benzamide 451' Exam le Structure Name H, m N_ { (1S, 2R)-2-hydroxy-1_ , ¢4Ht [(hydroxyamino) carbonyl] propyl}-4-{[3-438 5 (morpholin-4- °'L ylmethyl) phenyl] ethynyl} benzamide 452 "aC H OH Chlral 4- [ (3- { [ (2- 'OH aminoethyl) amino] methyl) phenyl) ethynyl]-N- Y)] y} p y) y] 411. 5 "="p i { (1S, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 453 453 'OH Ch ! I>y'OH N- [ (lR)-2- (hydroxyamino)-I- (hydroxymethyl) H 0 2-oxoethyl]-4'-propyl-1, I'-biphenyl-4-343. 4 H, C"O carboxamide HC 454 3 fOH N-[l->-hydroxycarbamoylmethyl) (lR, 2R)-2- ws hydroxypropyl] [4-(2-353. 4 H phenylethynyl) phenyl] carboxamide 455 H3 pH3chm 4'-ethyl-N- [ (1R, 2R)-1- 0 NS [(hydroxyamino) carbonyl]-2-7 4 H3C/ » O otNòH (methyloxy) propyl]-l, 1'-biphenyl-4-35 carboxamide 456 crcnm 4'-ethyl-N- [ (1S)-1- [ (ethylamino) methyl]-2- b ROH (hYdroxYamino)-2-oxoethyl]-1, l'-biphenyl-4-356. 4 carboxamide 457 b cnm 4'-etliyl-N- [ (1S)-2- (hydroxyamino)-2-oxo-1- H rNHK ({[(2S)-pyrrolidin-2-411 5 hneth 1 a 411. 5 c v/v i ° a"Y Y] no} methyl) ethyl]-1, 1'-biphenyl-4 carboxamide 458 ,-ccnm N_ [ (1S)-1- [ (ethylamino) methyl]-2- (hydroxyamino)-2-oxoethyl]-4-352. 4 O O OH (phenylethynyl) benzamide 459 459 Chiral N- S)-2-(hydroxyamino)-2-oxo-1-({[(2S)- pyrrolidin-2-yhnethyl] amino) methyl) ethyl]-4- 407. 5 s, MNH (phenylethynyl) benzamide 460 Exam le Structure Name Mg+ H, c from 3 f CH3 4'-ethyl-N-((1 S)-2-(hydroxyamino)-1- {[(1- methylethyl) amino] methyl}-2-oxoethyl)-1, 1'- 370. 5 H3o 0 oH biphenyl-4-carboxamide 461 _cohm 4-ethyl-N- [ ( 1 S)-2- (hydroxyamino)-1- ( { [2- HN+H (methylamino) ethyl jamino} methyl)-2-385. 5 0 0 OH oxoethyl]-1, 1'-biphenyl-4-carboxarnide 462 462 , CHch !) ai X 4'-ethyl-N-((1 S)-2-(hydroxyamino)-1- { [(1- methylpiperidin-4-yl) amino] methyl}-2- 425. 5 oxoethyl)-1, 1'-biphenyl-4-carboxamide 3 463 F C H3 N- ((1 S)-2- (hydroxyamino)-1- { [(1- methylethyl) amino] methyl}-2-oxoethyl)-4-366. 4 So ot OH (phenylethynyl) benzamide 464 N- [ (lS)-2- (hydroxyamino)-l- (1 [2- (methylamino) ethyl] amino} methyl)-2- 381. 4 oxoeth 1-4 hen leth 1 benzamide oOH Y]- (P Y YnY) 465 , CH3Chiral N- ( (ls)-2- (hydroxyamino)-1- { [ (1_ methylpiperidin-4-yl) amino] methyl}-2- 421. 5 oxoethyl)-4- (phenylethynyl) benzamide 0 0 OH 466 NH, choral N 1 S)-l 2-aminoethyl) amino methyl}-2- (hydroxyamino)-2-oxoethyl]-4-367. 4 o nom (phenylethynyl) benzamide 467 eNH2 N_ [ (1S)-1- { [bis (2-aminoethyl) amino] methyl}- H {N 2-(hydroxyarnino)-2-oxoethyl]-4-410. 5 0 0 OH (phenylethynyl) benzamide 468 H H Chlra, N- { (1S, 2R)-2-hydroxy-1- 0 [ (hydroxyaniino) carbonyllpropyll-4- ( {4- 481. 5 r 1- 40). 0 D-x [ (morpholin-4- 469 ylacetyl) amino] phenyl} ethynyl) benzamide 469 Example Structure Name MH+ H, ° H OH Chiral AM N- { (lS, 2R)-2-hydroxy-l- ti [ (hydroxyamino) carbonyl] propyl}-4- { [4- 410. 4 H, C_J (propanoylamino) phenyl] ethynyl} benzamide 470 - o"Tjj N- { (IS, 2R)-2-hydroxy-1- iH0 [ (hydroxyamino) carbonyl] propyl}-4- (14- F F, < [(trifluoromethyl) oxy] phenyl} ethynyl) benzami du 471 Chiraì 1, 1-dimethylethyl (2S)-3- (hydroxyamino)-3- zu "'"oxo-2- { [ (4- { [3_ 0 (propanoylamino) phenyl] ethynyl} phenyl) carb ", °'1rp v onyl] amino} propylcarbamate 472 0 6c CH Chiral 1, 1-dimethylethyl (2S)-3- (hydroxyamino)-3- b OH oxo-2-f [ (4-pent-1- 390. 4 o H ynylphenyl) carbonyl] amino} propylcarbamate i 473"o NH Chiral OH N- [ (IS)-l- (aminomethyl)-2- (hydroxyaniino)-2. H N oxoethyl]-4-{[3-395. 4 0 (propanoylamino) phenyl] ethynyl} benzamide 474 o NH Chiral jj {H OH N- [ (IS)-l- (aniinomethyl)-2- (hydroxyamino)-2. oxoethyl]-4-pent-1-ynylbenzarnide H3C 475 H H /N. N NHZ (S 4- (phenyloxy) benzaldehyde thiosemicarbazone 272. 3 476 H H I-zN NyNH2 4- (phenyloxy) benzaldehyde semicarbazone 256. 3 477 HO 'z N'NyNH, 4-1 [3- F o Wsl (trifluoromethyl) phenyl] oxy} benzaldehyde 340. 3 F thiosemicarbazone 478 Example Structure Name MH+ H3C H OH C « iral O N-ToH 4- [ (3, 4-difluorophenyt) efhynyl]-N- { (lS, 2R)-2- hydroxy-1-375. 3 FFv' [(hydroxyamino) carbonyl] propyl} benzamide 479 HCHChiral 3OH OH 4- [ (2, 4-dioxo-1, 2, 3, 4-tetrahydropyrirnidin-5- yl) ethynyl]-N-f (I S, 2R)-2-hydroxy- 1-373. 3 I j [(hydroxyamino) carbonyl] propyl} benzamide 480 480" N- [ (1S)-l- (aminomethyl)-2- (hydroxyamino)-2 -4- (4-phenylbuta-1, 3- diynyl) benzamide 481 HAN Chlral m XN OH N-[(1S)-l-(aminomethyl)-2-(hydroxyamino)-2 f vJ HN oxoethyl]-4'-propyl-1, 1'-biphenyl-4-342. 4 carboxamide 482 HzN Chlral O M-. H N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2. >/oxoethyl]-1, 1': 4', 1"-terphenyl-4-carboxamide 376. 4 483 -- H3Cs_OH Chlr. 31 6g 1_N-OH N-{(lS, 2R)-2-hydroxy-1- vJ H ao [(hydroxyamino) carbonyl] propyl}-1, 1' : 4, 1"-391. 4 terphenyl-4-carboxamide 484 H, a,, rat C'INH 1, 1-dimethylethyl (2S)-2- [ ( {4- [ (4- { [ ( { [ (1, 1- N0'OH dimethylethyl) oxy] carbonyl} amino) acetyl] ami no} phenyl) ethynyl] phenyl} carbonyl) arnino]-3- (hydroxyamino)-3-oxopropylcarbamate 485 H C Li OH Chiral O Jk f NH N-[(1S, 2R)-1-(hydrazinocarbonyl)-2- H drox hydroxypropyl]-4- (phenylethynyl) benzamide 338. 4 486 4 6 FiC H OH ° Chiral vNHto H 2 2-[(2Sf3R)-3-hydroxy-2-({[4- (phenylethynyl) phenyl] carbonyl} amino) butano 381. 4 yl] hydrazinecarboxamide 487 Example structure Name MH+ FC H Chiral > iNoH N-{(lS, 2R)-2-hydroxy-1- Ho [ (hydroxyamino) carbonyl] propyl}-4- [ (2- 353. 4 methylphenyl) ethynyl] benzamide 488 H, C H OH Chiral go XN>OH N- { (lS, 2R)-2-hydroxy-1- " [ (hydroxyamino) carbonyl] propyl}-4- [ (3- 355. 4 i "o v hydroxyphenyl) ethynyl] benzamide 489 H H OH Chirat N-M,. H 4- (13- [ (aminoacetyl) amino] phenyl} ethynyl)-N N H { (1S, 2R)-2-hydroxy-1- 411. 4 H2Nt < [(hydroxyamino) carbonyl] propyl} benzamide 490 °HoH Chkat 4_ { [4_ M, OH ( { [ (cyanomethyl) amino] acetyl} amino) phenyl] 450 5 ethynyl}-N- { (1S, 2R)-2-hydroxy-1- b [ (hydroxyamino) carbonyl] propyl} benzamide 491 X Chlral 4'-ethyl-N-{(lS)-2-(hydroxyamino)-2-oxo-1- Q [ (tetrahydro-2H-pyran-4- H ylamino) methyl] ethyl}-1, l-biphenyl-4- NC o o OH carboxamide 492 cnm N- { (1S)-2- (hydroxyamino)-2-oxo-1- [ (tetrahydro-2H-pyran-4- } i N ylamino) methyl] ethyl}-4- o 0 oH (phenylethynyl) benzamide 493 0, N-OH 4- [ (4-chlorophenyl) ethynyl]-N-I (IS, 2R)-2- hydroxy-l-373. 8 [ (hydroxyamino) carbonyl] propyl} benzamide 494 r""CH-oH°""'N- { (lS, 2R)-2-hydroxy-l- --D\-JLH [ (hydroxyamino) carbonyllpiropyll-4- [ (4- "° methylphenyl) ethynyl] benzamide 495 oHC OH Chm N-Y ; H-OH 4- [ (2-fluorophenyl) ethynyl]-N-I (lS, 2R)-2- "lof hydroxy-1-357. 4 [ (hydroxyamino) carbonyl] propyl} benzamide 496 Example Structure Name MH+ H3Cv, OH Chiral -OH 4- [ (3-fluorophenyl) ethynyl]-N-f (IS, 2R)-2- zozo hydroxy-1-357. 4 [ (hydroxyamino) carbonyl] propyl} benzamide F 497 HIC OH Chiral Ng N-O H 4- [(4-fluorophenyl) ethynyl]-N- { (1 S, 2R)-2- >_SH o hydroxy-l-357. 4 F\d [(hydroxyamino) carbonyl] propyl} benzamide 498 H, C. OH Ctlfrat 4- [ (4- °, <N~NH-OH {[(cyclopropylamino) acetyl] amino} phenyl) eth V, N99-HN ynyl]-N- {(1 S, 2R)-2-hydroxy-1- 499 [(hydroxyamino) carbonyl] propyl} benzamide 499 6c OH chl. 1 4- (14- [ (1 [2- 0 (ditnethylamiiao) ethyl] amino} acetyl) amino] ph 482 6 c lethynyl)-N- { (1 S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 500 H° OH °himl 4- ( {4- [ ( { [2- (acetylarnino) ethyl] amino} acetyl) amino] pheny H, C-DO Ilethynyl)-N-f (lS, 2R)-2-hydroxy- I-496. 5 o [(hydroxyamino) carbonyl] propyl} benzamide 501 N-{(1 S, 2R)-2-hydroxy-1- °"'° °"°"''°' [ (hydroxyamino) carbonyl] propyl}-4- ( {4- [ ( { [3- d-°" 0 (2-oxopyrrolidin-l-536. 6 yl) propyl] amino} acetyl) amino] phenyl} ethynyl 502) benzamide N- {(1 S, 2R)-2-hydroxy-1- 1 (hYdrOxYamino) carbonyllpropyl)-4- { [4- 0"'°" ( { [ (pyridin-3- 502. 5 yhnethyl) amino] acetyl} amino) phenyl] ethynyl} 503 benzamide N- { (lS, 2R)-2-hydroxy-l- ° NgN-OH [(hydroxyamino) carbonyl] propyl}-4- { [4- ( { [ (2- 0 pyridin-2-516. 6 ylethyl) amino] acetyl} amino) phenyl] ethynyl} b 504 enzamide H, C OH Chlr71 N-{(lS, 2R)-2-hydroxy-1- .-yX. JM-. H [ (hydroxyammo) carbonyl] propyl}-4- [ (4- { [ (4- methylpiperazin-l- yl) acetyl] amino} phenyl) ethynyl] benzamide 505 Exam le Structure 4- ( {4- [ ( 1, 4'-bipiperidm-1'- H, COH Ch ! fft 'L\ ? fYN"ir-"'°"yIacetyl) amuio] phenyl} ethynyl)-N- { (lS, 2R)-2- hydroxy-l- "--JL-r hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 506 1- (2- { [4- ( {4- [ ( { (1S 2R)-2-hydroxy-1- t5° °"°ntrei e 0 [ (hydroxyamino) carbonyl] propyl} amino) carbo cargo nyllphenyl} ethynyl) phenyl] amino}-2- oxoethyl) piperidine-4-carboxamide 507 H, OH . N- { (lS, 2R)-2-hydroxy-l- o [ (hydroxyaniino) carbonyl] propyll-4- [ (4- , N_) tHC { [(piperidin3 494. 6 ylamino) acetyl] amino} phenyl) ethynyl] benzam Y) h']} p Y) YnY] 508 ide N- { (lS, 2R)-2-hydroxy-l- jrv°'°"° [ (hydroxyamino) carbonyl] propyl}-4- [ (4- 0 f [ (piperidin-4- 494. 6 ylamino) acetyl] amino} phenyl) ethynyl] benzam 509 ide s- {(1 S, 2R)-2-hydroxy-1- n NgN-CH [(hydroxyaeiino) carbonyl] propyl}-4- { [4- NH bp, ; ° ( { [ (piperidin-2- 508. 6 yhnethyl) amino] acetyl} amino) phenyl] ethynyl} 510 benzamide N-{(lS, 2R)-2-hydroxy-1- ". °Y°" °'"" [ (hydroxyan] mo) carbonyl] propyl}-4- { [4- (f [ (piperidin-3- 508. 6 ylmethyl) amino] acetyl} amino) phenyl] ethynyl} 511 benzamide on H, OH Chllal 4-[(4-{[(3-aminopyrrolidin-1- r_ ; r p,-b-°"yl) acetyl] amino} phenyl) ethynyl]-N- { (1S, 2R)- "p 2-hydroxy-l-480. 5 [ (hydroxyamino) carbonyl] propyl} benzamide 512 oH, OH c 4- ( {4- [ (azepan-l- N-S--OH ylacetyl) aminojphenyl) ethynyl)-N-f (I S, 2R)-2. N D -'''a hydroxy-1-493. 6 513 [(hydroxyamino) carbonyl] propyl} benzarnide 513 N-{(1S, 2R)-2-hydroxy-1- "'° °'" [ (hydroxyamino) carbonyl] propyl}-4- { [4- ( { [ (4- rpholin-4-572. 6 ylphenyl) amino] acetyl} amino) phenyl] ethynyl} 514 benzamide ExampleStructureNameMH+ N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2 0 Ny N-OH oxoethyl]-4-f [4- ( { [ (2- HO~"N) LHv O hydroxyethyl) amino] acetyl} amino) phenyl] ethy 515 nyl} benzamide 515 N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 oxoethyl]-4- [ (4- p N-W ° {[(cyclopropylamino) acetyl] amino} phenyl) eth ynyl] benzamide 516 N- [ ( 1 S)-1- (ammomethyl)-2- (hydroxyammo)-2' » 4N-OH oxoethyl]-4-({4-[({[3-(2-oxopyrrolidin-1-521 6 <Ns, HgNe yl) propyl] amino} acetyl) amino] phenyl} ethynyl 517) benzamide 517 0ItN N- [ (IS)-I- (aniinomethyl)-2- (hydroxyamino)-2. Hzon wH o oxoethyl]-4-[(4-{[(4-methylpiperazin-1-479. 6 yl) acetyl] amino} phenyl) ethynyl] benzamide 518 N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2 vEiXo oxoethyl] 4 { [4- (f [ (pyridin-3- XNSEHV yhmethyl) amino] acetyl} amino) phenyl] ethynyl} benzamide 519 kN-OH °""'N- [ (1S)-l- (aminomethyl)-2- (hydroxyamino)-2 g) O 2H oxoethyl]-4-({4-[(piperidin-1-464. 5 ylacetyl) amino] phenyl} ethynyl) benzamide 520 H, OH Chlnl 4 {[4 ({[(2 ° °X,, hydroxyethyl) amino] acetyl} amino) phenyl] ethy a 455. 5 HO"-m--JL-nyl)-N-I (lS, 2R)-2-hydroxy-l- [ (hydroxyamino) carbonyl] propyl} benzamide 521 N- { (lS, 2R)-2-hydroxy-l- , ° °" [ (hydroxyamino) carbonyl] propyl}-4-({4-[({[2-469 5 (methyloxy) ethyl] amino} acetyl) amino] phenyl} ethynyl) benzamide 522 N- {(1 S, 2R)-2-hydroxy-1- H. aNgN-CH [(hydroxyamino) carbonyl] propyl}-4-({4- [ (fmethyl [2- 483. 5 (methyloxy) ethyl] amino} acetyl) amino] phenyl} 523 ethynyl) benzamide Example Structure Name MH+ H, 4- { [4-C { [ [2_ (dirnethylamino) ethyl] (methyl) amino] acetyl} a mino) phenyl] ethynyl}-N- { (1 S, 2R) 2hydroxy l-[(hydroxyamino) carbonyl] propyl} benzamide 524 4- { [4- ( { [ (3R)-3- (dimethylamino) pyrrolidin-1- ) 6c-N'PH. yl] acetyllamino) phenyl] ethynyll-N-I (lS, 2R)- 2-hydroxy-l-508. 6 525 [(hydroxyamino) carbonyl] propyl} benzamide 525 H, OH OH Chlral 4- { [4- ( { [ (3S)-3- (dimethylamino) pyrrolidin-1- ;, _ p-b-°H yl] acetyl} amino) phenyl] ethynyll-N-f (lS, 2R)- p 2-hydroxy-1-508. 6 526 (hydroxyamino) carbonyl] propyl} benzamide 526 4- { [4- ( { [ (3R)-3- (acetylamino) pyrrolidin-1- H, C wN4N-oH yl3 acetyl} amino) phenyl] ethynyl}-N- { (lS, 2R)- g (- 2hydroxy1- 527 (hydroxyamino) carbonyl] propyl} benzamide 527 4- { [4-C { [C3s)-3-Cacetylamino) pyn'olidin-1- ° °° °H °, , a H, CA N A _HHNiN-OH yl] acetyl} amino) phenyl] ethynyl}-N- { (lS, 2R)- CN a 2-hydroxy-1- 528 [(hydroxyamino) carbonyl] propyl} benzamide 528 voH c 4- { [4- ( { [ (3R)-l-azabicyclo [2. 2. 2] oct-3- O _SH~HN-OH ylamino] acetyl} amino) phenyl] ethynyl}-N-520 6 I (lS, 2R)-2-hydroxy-l-. 520. 6 529 (hydroxyamino) carbonyl] propyl} benzamide 529 H, 4- { [4- ( { [ (3S)-l-azabicyclo [2. 2. 2] oct-3- 0 ylamino] acetyl} amino) phenyl] ethynyl}-N-520 6 { (1S, 2R)-2-hydroxy-1- 530 [(hydroxyamino) carbonyl] propyl} benzamide 530 N-{(lS, 2R)-2-hydroxy-1- ffi gN-OH [(hydroxyamino) carbonyl] propyl}-4-({4- NH pp ! : b ° 2R olidin-2-494. 6 ll [C { [C)-px yhnethyl] amino} acetyl) arnino] phenyl} ethynyl) 531 benzamide N- { ( 1 S, 2R)-2-hydroxy-1- at- [ (hydroxyamino) carbonyl] propyll-4- ( {4- //--\,,-JLH, LyW-OH [ ( { [ (2S)-pyrrolidin-2- 494. 6 yhnethyl] amino} acetyl) amino] phenyl} ethynyl) 532 benzamide Example Structure Name MH+ % C OH Chi.] 4-f [4- (f [ (3- a' ra-° aminocyclohexyl) amino] acetyl} amino) phenyl] 508. 6 ", N 1 I p ethynyl}-N- { (1S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 533 oH, oH ch,,.. N- { (lS, 2R)-2-hydroxy-l- [ (hydroxyairiino) carbonyllpropyl}-4- [ (4- f [ (3- 495. 5 HO hydroxypiperidin-1- yl) acetyl] amino} phenyl) ethynyl] benzamide 534 N- { (lS, 2R)-2-hydroxy-1- MoH c.. . [ (hydroxyamino) carbonyl] propyl}-4- { [4- ( { [ (3- . Lb-OH morpholin-4-538. 6 ylpropyl) amino] acetyl} amino) phenyl] ethynyl} 535 benzamide 535 N- { (lS, 2R)-2-hydroxy-l- 1 (hYdrOxYamino) carbonyllpropyll-4-1 [4- (f [ (2- methylpropyl) amino] acetyl} amino) phenyl] eth ynyl} benzamide 536 H, C OH Chinl 4-[(4- 1 [ (ethylaniino) acetyl] amino} phenyl) ethynyl]- 0 N-I (IS, 2R)-2-hydroxy-l- 439. 5 [(hydroxyamino) carbonyl] propyl} benzamide 537 u fO ... N- { (lS, 2R)-2-hydroxy-l- C o wH ; HN-OH [(hydroxyammo) carbonyl] propyl}-4-({4-479. 5 NJ4H [(pipendin1 ylacetyl) amino] phenyl} ethynyl) benzamide 538 , ° °H ", , N- { (1S, 2R)-2-hydroxy-1- H. C, OH mM ''' vNX [(hydroxyamino) carbonyl] propyl}-4- { [4- ( { [ (3- 469. 5 hydroxypropyl) aniino] acetyl) amino) phenyl] et hynyl} benzamide 539 N-{(lS, 2R)-2-hydroxy-1- H, C, OH ChRal px,-a-°" [ (hydroxyamino) carbonyl] propyl}-4- ( {4- [ ( { [3- 483. 5 (methyloxy) propyl] amino} acetyl) amino] pheny 1} ethynyl) benzamide 540 H, OH Chllul {[ ({[( cyanoethyl) amino] acetyl} amino) phenyl] ethyl a yl}-N- { (1 S, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 541 Example structure Name MH+ . N-{(lS, 2R)-2-hydroxy-1- H gN-OH [(hydroxyarnino) carbonyl] propyl}-4- { [4- ( { [ (2- pyrrolidin-l-508. 6 ylethyl) amino] acetyl} amino) phenyl] ethynyl} b 542 enzamide coH ch ! r. ! N- { (lS, 2R)-2-hydroxy-l- r ; = r b'O p °" [ (hydroxyamino) carbonyl] propyl}-4- [ (4- { [ (2- Y b methyl-lH-imidazol-1- yl) acetyl] amino} phenyl) ethynyl] benzamide 543 "aN Chlml N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 r r ° p-b-°"oxoethyl]-4- [ (4- meth lamino ace 1 amino hen 1 eth 1 410. 4 benzamide 544 ttN Chi. 1 N- [ S)-1-(aminomethyl)-2-(hydroxyamino)-2 SH4N-OH oxoethyl] 4 {[4-({[(2 452 5 methylpropyl) amino] acetyllamino) phenyl] eth ynyl} benzamide 545 , N- [ (lS)-l- (amijiomefhyl)-2- (liydroxyammo)-2 H) Y H-OH oxoethyl]-4- (14- [ (1 [2- 454. 5 (methyloxy) ethyl] amino} acetyl) amino] phenyl} ethynyl) benzamide 546 ",",, , N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 ° _ r ° p-b-°"oxoethyl]-4- ( {4- [ ( {methyl [2- (methyloxy) ethyl] amino} acetyl) amino] phenyl} ethynyl) benzamide 547 H, N- [ ( S)-1- (aminomethyl)-2- (hydroxyamino)-2 , 0-" oxoethyl]-4- { [4- ( { [(3 454 5 HO HNJLhNr hydroxypropyl) amino] acetyl} amino) phenyl] et hynyl} benzamide 548 N- [ ( 1 S)-1- (aminomethyl)-2- (hydroxyamino)-2 ,-p-°"°hm oxoethyl]-4- ( {4- [ ( { [3-468. 5 (methyloxy) propyl] aniinolacetyl) amino] pheny 1} ethynyl) benzamide 549 n, N 1 N- [ (IS)-I- (aminomethyl)-2- (hydroxyaraino)-2. _/p'1rb-°"oxoethyl]-4- ( {4- [ ( { [2- HCwN~NfaHe (dimethylamino) ethyl] amino} acetyl) amino] ph enyl} ethynyl) benzamide 550 Example Structure Name o" N ro N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 c 0 oxoetliyl]-4-f [4- (f [ [2- H, ON~N U>HN (dimethylamino) ethyl] (methyl) amino] acetyl} a mino) phenyl] ethynyl} benzamide 551 H, N Chlnll ( { [( { [2 0 N-OH (acetylamino) efllyl] aminolacetyl) aniino] pheny 481. 5 Ilethynyl)-N- [ ( 1 S)-1- (aminomethyl)-2- (hydroxyamino)-2-oxoethyl] benzamide 552 N- [ ( 1 S)-1- (aminomethyl)-2- (hydroxyamino)-2 O e HX oxo ethyl]-4- { [4 ( { [ zig cyanoethyl) amino] acetyl} amino) phenyl] ethyn yl} benzamide 553 n. N mn,. N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 O _HNk N-OH oxoethyl]-4 { [4-( { [(2pyrrolidin1 4 9 3 6 ylethyl) amino] acetyl} amino) phenyl] ethynyl} b enzamide 554 H, N Chlml N- [ S)-1-(aminomethyl)-2-(hydroxyamino)-2 .. oxoethyl]-4- ( {4- [ ( { [4- ggg CH (ditnethylamino) butyl] amino} acetyl) amino] ph CH enyl} ethynyl) benzamide 555 HiN °'""N- [ (lS)-l- (amuiomethyl)-2- (hydroxyamino)-2. 0E w O oxoethyl]-4-({4-[(morpholin-4-466. 5 ylacetyl) amino] phenyl} ethynyl) benzamide 556 oH2N) kN-OH N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 N-OH oxoethyl]-4- (f4- [ (azepan-l- 478. 6 N H ylacetyl) amino] phenyl} ethynyl) benzamide F 557 XN-OH °'""N- [ (lS)-l- (anunomethyI)-2- (hydroxyammo)-2 oxoethyl]-4- (f4- [ (pyrrolidin-l- 450. 5 ylacetyl) amino] phenyl} ethynyl) benzamide 558 1-12- [ (4-f [4- (I [ (IS)-I- (aniinomethyl)-2- ''-) °'"" (hydroxyammo)-2- 0 0 oy oxoeth-vl-laniino} carbonyl) phenyl] ethynyl} phe 507. 6 nyl) amino]-2-oxoethyl} piperidine-4- 559 carboxamide Example Structure Name MH+ 4- { [4- ( { [ (3R)-3- (acetylamino) pyrrolidin-1- H, H H h, a H, C1N, o __¢ » HNX yl] acetyl} amino) phenyl] ethynyll-N- [ (IS)-I- (aminomethyl)-2- (hydroxyamino)-2- 560 oxoethyl] benzamide 560 , N °h" N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 -f) ° oxoethyl]-4- { [4- ( { [ (3R)-3- NHN (dimethylamino) pyrrolidin-1- 561 yl] acetyl} amino) phenyl] ethynyl} benzamide 561 °'N Chlnl N-[(1 S)-1-(aminomethyl)-2-(hydroxyamino)-2 HNc > wHk-OH oxoethyl]-4-[(4-{[(3-arninopyrrolidin-1-465. 5 yl) acetyl] amino} phenyl) ethynyl] benzamide 562 HzN N 1 N- [ (IS)-I- (atninomethyl)-2- (hydroxyaniino)-2. H-OH oxoethyl]-4- [ (4-f [ (piperidin-3- HN, amino) acetyl] amino} phenyl) ethynyl] benzam ide 563 H, Chl. 1 N- [ (IS)-I- (aminomethyl)-2- (hydroxyaniino)-2. _, b-'b-°"oxoethyl]-4- [ (4- { [ (piperidin-4- N N ylarnino) acetyl] amino} phenyl) ethynyl] benzam ide 564 H, cNf,. N- [ (lS)-l- (aminomethyl)-2- (hydroxyanmio)-2' NH p r = ° pp-°"oxoethyl]-4- { [4- ( { [ (piperidin-2- 493. 6 a yhnethyl) amino] acetyl} amino) phenyl] ethynyl} benzamide 565 HzN N 1 N- [ (IS)-I- (aminomethyl)-2- (hydroxyaniino)-2, H-OH oxoethyl]-4-1 [4- (I [ (piperidin-3- -ba p ° yhnethyl) amino] acetyl} amino) phenyl] ethynyl} benzamide 566 n, N ch. N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2. YH-OH oxoethyl]-4- { [4- (f [ (pyridin-2- 487. 5 Ylmethyl) amino] acetyl) aniino) phenyl] ethynyl} benzamide 567 H, N chM. N- [ (lS)-l- (an] inomethyl)-2- (hydroxyamino)-2 R-OH oxoethyl]-4-f [4- (I [ (pyridin-4- 0 yhilethyl) amino] acetyl} amino) phenyl] ethynyl} benzamide 568 Example structure Name MIl+ N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 _@H o oxo ethyl]-4- { [4 ( { [ (2-pyridin-2- 501. 6 ylethyl) amino] acetyllamino) phenyl] ethynyl} b enzamide 569 n, N ChlMl N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 p'lo b-°"oxoethyl]-4- { [4- ( { [(2-pyridin-3- 501. 6 methyl) amino] acetyl} amino) phenyl] ethynyl} b enzamide 570 H, N chu, l N- [ S)-1-(aminomethyl)-2-(hydroxyamino)-2 _ i ; p'1o b-°"oxoethyl]-4- { [4- ( { [ (2-pyridin-4- 501. 6 , 3~N N ylethyl) amino] acetyl} amino) phenyl] ethynyl} b enzamide 571 o" N ch ! N- [ (lS)-l- (ammomethyl)-2- (hydroxyamino)-2- ° _C<N4N-OH oxoethyl]-4 [(4 472 5 , HNH {[(phenylamino) acetyl] amino} phenyl) ethynyl] benzamide 572 H, N- [ (lS)-l- (ammomemyl)-2- (hydroxyamino)-2. 8% H4N-OH oxoethyl]-4 {[4 0 ( { [ (phenyhnethyl) aminolacetyl} ethynyl} benzamide 573 n, N o,. N- [ (lS)-l- (aminomethyl)-2- (hydroxyammo)-2- p'1o'b-°"oxoethyl]-4- { [4- ( { [ (2- 500. 6 phenylethyl) amino] acetyl} amino) phenyl] ethyn yl} benzamide 574 c.... N- [ (lS)-l- (aminomethyl)-2- (hydioxyammo)-2 ? r'°" oxoemyl]-4- ( {4- [ (lH-imidazol-l- 447. 5 NVN tNH ylacetyl) amino] phenyl} ethynyl) benzamide 575 °FhC OH Chlral N- { (lS, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyllpropyll-4- (14- [ (IH- 462. 5 N/=\N N iInidazol1 ylacetyl) amino] phenyl} ethynyl) benzamide 576 coH ch, N- { (lS, 2R)-2-hydroxy-l- [ (hydroxyamino) carbonyllpropyl}-4- [ (4- O-a { [ (phenylamino) acetyl] amino} phenyl) ethynyl] benzamide 577 Example structure Name MH+ H, c..... N- { (lS, 2R)-2-hydroxy-l- o _, 'p-H [ (hydroxyamino) carbonyl] propyl}-4- { [4- (f [ (2- phenylethyl) amino] acetyl} amino) phenyl] ethyn yl} benzamide 578 N- { (lS, 2R)-2-hydroxy-l- U-OH [ (hYdroxyaniino) carbonyljpropyll-4-1 [4- (I [ (3- 0 C HitHe-phenylpropyl) amino] acetyl} amino) phenyl] ethy nyl} benzamide 579 H, C H OH Chlral 0) H-" a J9HF OH {[(aminoacetyl) amino] methyl} phenyl) ethynyl] 425 5 ..- ° N- { (lS, 2R)-2-hydroxy-l- 580 (hydroxyamino) carbonyl] propyl} benzamide 580 H, C H OH Chiral 4- [ (2-aminopyrimidin-5-yl) ethynyl]-N- AS {(1 S, 2R)-2-hydroxy-1-356. 4 ANm [(hydroxyamino) carbonyl] propyl} benzamide 581 581 H c L4 OH Chiral 4- [ (4-acetylphenyl) ethynyl]-N- { (1S, 2R)-2- hydroxy-l-381. 4 H3C yo [ (hYdroxYamino) carbonyl] propyl} benzamide 582 N- { (lS, 2R)-2-hydroxy-l- px,-a, o" [ (hydroxyamino) carbonyl] propyl}-4- [ (4- { [ ( {2- [4- (phenyhnethyl) piperazin-1- 613. 7 O N9~ H yl] ethyl} amino) acetyl] amino} phenyl) ethynyl] b 583 enzamide UOJ . - 4. 4. a"op°H ( { [ (aminoacetyl) amino] acetyl} amino) phenyl] e 468. 5 HjjQ <hynyl}-N- { (lS, 2R)-2-hydroxy-l- H [(hydroxyamino) carbonyl] propyl} benzamide 584 j<, c"oH °' 4- { [4- ( { [4- (2-hydroxyethyl) piperazm-l- 0 yell acetyl} amino) phenyl] ethynyl}-N-{(l S, 2R)-524 6 N 2-hydroxy-l- a [ (hydroxyamino) carbonyl] propyl} benzamide 585 O Chiral <, 901, OH hlml N-{(lS, 2R)-2-hydroxy-1- C, HN ; N [(hydroxyamino) carbonyl] propyl}-4-({4-57 1 : F [ (trifluoroacetyl) amino] pyrrolidin-1- F F F yl} acetyl) amino] phenyl} ethynyl) benzamide 586 Exam le Structure Name mp o c.,., N- { (lS, 2R)-2-hydroxy-l- 'H H » CH>OH [(hydroxyamino) carbonyl] propyl}-4-[(4-42 { [ (methylammo) acetyl] amino} phenyl) ethynyl] 425. 5 benzamide 587 o Chm N- { (lS, 2R)-2-hydroxy-1- OH [ (hydroxyanlino) carbonyllpropyll-4- (f4- H 480. 5 H H N [(piperazin1 ylacetyl) amino] phenyl} ethynyl) benzamide 588 N-{(lS, 2R)-2-hydroxy-1- OH ChlAl [(hydroxyarnino) carbonyl] propyl}-4-{[4- S [ (pyridin-2- 502. 5 g OH ylmethyl) amino] acetyl} amino) phenyl] ethynyl} Y Y)] tY}) p Y] YnY} 589 benzamide 5oM N- { ((lS, 2R)-2-hydroxy-1- o Chiral [(hydroxyamino) carbonyl] propyl}-4-{[4- p r v-r p" ( { [ (pYridin-4- 502. 5 4OH or OH ylmethyl) amino] acetyl} amino) phenyl] ethynyl} 590 benzamide oU N- { ( 1 S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl}-4- { [4- ( { [ (2- C H XN pyridin-3-5 16. 6 OH ylethyl) amino] acetyl} arnino) phenyl] ethynyl} b - Q. enzamide N- { (lS, 2R)-2-hydroxy-1- cic 0 [ (hydroxyamino) carbonyl] propyll-4-1 [4- (f [ (2- m 4 pyridin-4-516. 6 methyl) amino] acetyl} amino) phenyl] ethynyl} b 592 enzamide . c. 4- ( {4- [ ( { [ (2- N<N<oi>OH fluorophenyl) methyl] amino} acetyl) amino] phe 519 5 eF H o>_9NòH nyl} ethynyl)-N-{(lsß2R)-2-hydroxy-l- [(hydroxyamino) carbonyl] propyl} benzamide 593 Chlral 4 ( {4 [( { [(2 _ p ! _ ! °'° °"chlorophenyl) methyl] amino} acetyl) amino] phe Oa H Os « OH nyl} ethynyl)-N-{(lS, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 594 O Chlxal N-{(1S, 2R)-2-hydroxy-1- Nn4 o + SOH [(hydroxyamino) carbonyl] propyl}-4-[(4-{[({[2 531 6 °-°" (methyloxy) phenyl] methyl} amino) acetyl] amin o} phenyl) ethynyl] benzamide 595 Example Structure Name MH+ o c.... 4- ( {4- [ ( { [ (3- fluorophenyl) mefliyl] amino) acetyl) amino] phe OH o OH nyl} ethynyl)-N-{(lS, 2R)-2-hydroxy-1- 596 [(hydroxyamino) carbonyl] propyl} benzamide 596 4- (f4- [ (f [ (3- s=HN H <tOH chlorophenyl) methyl] amino} acetyl) amino] phe 536 0 (W o NOH nyl} ethynyl)-N-{(lS, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 597 Chl. 1 N- { (IS, 2R)-2-hydroxy-l- [ (hydroxyamino) carbonyl] propyl}-4- [ (4-1 [ (f [3 N-qoH (methyloxy) phenyl] methyl} amino) acetyl] amin O-°H, o} plienyl) ethynyl] benzamide 598 Chlral N- {(1 S, 2R)-2-hydroxy-1- [ (hYdroxYamino) carbonyllpropyl}-4- (f4- [ (f [ (3 °-°H methylphenyl) methyl] amino} acetyl) amino] phe nyl} ethynyl) benzamide 599 re° c. N- { (lS, 2R)-2-hydroxy-l- H r v-r v. p- a" [ (hydroxyamino) carbonyl] propyl}-4- [ (4- { [ ( { [3 569. 5 - O" (trifluoromethyl) phenyl] methyl} amino) acetyl] 600 F F amino} phenyl) ethynyl] benzamide 600 N- { (lS, 2R)-2-hydroxy-l- , N-C-1 (hYdroxYanlino) carbonyllpropyll-4-1 [4- v r F °a H (f [ ( {3- 585. 5 F [(trifluoromethyl) oxy] phenyl} methyl) amino] ac 601 etyl} amino) phenyl] ethynyl} benzamide ° , . 4- ( {4- [ ( { [ (4- fluorophenyl) methyl] amino} acetyl) amino] phe °a-a H nyl} ethynyl)-N-{(lS, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 602 ahlral N- {(1 S, 2R)-2-hydroxy-1- [ (hYdrOxYamino) carbonyllpropyll-4- (f4- [ (f [ (4 ° -°H methylphenyl) methyl] amino} acetyl) amino] phe nyl} ethynyl) benzamide 603 a. M 4- [ (4- { [ ( { [4- (dirnethylamino) phenyl] methyl} amino) acetyl] 544. 6 aminolphenyl) ethynyl]-N- { (IS, 2R)-2-hydroxy 1- [ (hydroxyamino) carbonyl] propyl} benzamide 604 Example Structure Name MH+ ., N- { (lS, 2R)-2-hydroxy-l- p-" [ (hydroxyamino) carbonyl] propyll-4- [ (4- f [ (f [4 569. 5 F (trifluoromethyl) phenyl] methyl} amino) acetyl] F F 605 amino} phenyl) ethynyl] benzamide 605 rt0 Chl. 1 4- [ (4-f [ (f [4-fluoro-2- F (trifluoromethyl) phenyl] methyl} amino) acetyl] mF o NOH amino} phenyl) ethynyl]-N- { S, 2R)-2-hydroxy 606 [ (hydroxyamino) carbonyl] propyl} benzamide 606 4- (14- [ (f [ (2, 4- difluorophenyl) methyl] amino} acetyl) amino] ph 537 5 F O OH enyl} ethynyl)-N-{(lS, 2R)-2-hydroxy-1- F 607 (hydroxyamino) carbonyl] propyl} benzamide 607 Chl. 1 4- (14- [ (1 [ (2, 4- H dichlorophenyl) methyl] amino} acetyl) amino] p v o ° a" henyl} ethynyl)-N- { (1S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 608 . 0 .. 4- { [4- ( { [ (2- OH fluorophenyl) aniino] acetyllanlino) phenyllethy F O"--O"nyl}-N- { (1S, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 609 4-f [4- (f [ (4- Ft3NH H 9o>OH fluorophenyl) amino] acetyl} amino) phenyl] ethy 50 5 H nyl}-N- { (lS, 2R)-2-hydroxy-l- [(hydroxyamino) carbonyl] propyl} benzamide 610 Chiml 4- (f4- [ ( { [ (3, 5- p' _ ! p j-°"difluorophenyl) methyl] amino} acetyl) amino] ph '"Q oH enyI} ethynyl)-N- { (lS, 2R)-2-hydroxy-l- F [ (hydroxyamino) carbonyl] propyl} benzamide 611 4- { [4- ( { [ (4- B, <=@>OH bromophenyl) amino] acetyl} amino) phenyl] ethy - nyl}-N- { (lS, 2R)-2-hydroxy-l- [ (hydroxyamino) carbonyl] propyl} benzamide 612 4- ( {4- [ ( { [4- 0 Ct) M H O'Nt3H<H <OS (dimethylamino) phenyl] amino} acetyl) amino] p H a"henyl} ethynyl)-N- { (1S, 2R)-2-hydroxy-1- 530. 6 613 [(hydroxyamino) carbonyl] propyl} benzamide 613 Example Structure Name MH+ HN Chiral N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 O ßS4N-oH oxoethyl]-4-[(4-{[(2S)-2-410 4 "" /\ pp °N amino ro ano lalmino (4hen21 eth CH niide CH mide 614 n, N ch ! N- [ (lS)-l- (ammomethyl)-2- (hydroxyamino)-2' han b-°"oxoethyl]-4- [ (4- { [ (2R)-2_ 410. 4 -v-M aminopropanoyl] amino} phenyl) ethynyl] benza mide 615 HxN Chiral ° XN-OH N- [(1 S)-1-(aminomethyl)-2-(hydroxyamino)-2 oxoethyl]-4- [ (4-1 [ (2S)-2-amino-4- 452. 5 methylpentanoyl] amino} phenyl) ethynyl] benza mide 616 o N "'''4- [ (4- { [ (2S, 3R)-2-amino-3- a-li'b-oH hydroxybutanoyl] amino} phenyl) ethynyl]-N- "''b [ (1S)-1- (ami. nomethyl)-2- (hydroxyamino)-2- 440. 5 H, C OH oxoethyl] benzamide 617 HxN b-°H 4- [ (4- { [ (2S)-2-0-4- H Ns eHN o cyanobutanoyl] amino} phenyl) ethynyl]-N-449 5 HxN - [ (lS)-l- (aminomethyl)-2- (hydroxyamuio)-2- N oxoethyl] benzamide 618 0f-6N Chl r21 N- [(1 S)-1-(aminomethyl)-2-(hydroxyamino)-2 rX , M-. H oxoethyl]-4- [ (4-f [ (2S)-2, 3- p P Y]} P Y) ynY] 425. 5 b diaminopropanoyl] amino henyl) ethynyl] benz NH2 amide 619 n, N (2S)-N- (4- { [4- ( { [ (lS)-l- (ammomethyl)-2- °, v ; p'O °" (hydroxyamino)-2_ 436. 5 zu oxoethyl] amino} carbonyl) phenyl] ethynyl} phe nyl) pyrrolidine-2-carboxamide 620 H2N c.. (2S)-N- (4- { [4- ( { [ (lS)-l- (ammomethyl)-2- W) Y (hydroxyamino)-2- 450. 5 cx N oxoethyl] amino} carbonyl) phenyl] ethynyl} phe nyl) piperidine-2-carboxamide 621 N N- (4 { [4 ( { [ (1S)-1- (aminomethyl)-2- H) Y (hydroxyamino)-2- XHN oxoethyl] amino} carbonyl) phenyl] ethynyl} phe nyl) piperidine-3-carboxamide 622 Exam le Structure Name N Chiral b-o"4- [ (4- { [ (2S)-2-amino-3- (1H-imidazol-4- yl) propanoyl] aminolphenyl) ethynyl]-N- [ (lS)- 1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl] benzamide 623 0han H 'N- [ (lS)-l- (ammomethyl)-2- (hydroxyammo)-2. -< Ht oxoethyl]-4-[(4-338. 4 0 methylphenyl) ethynyl] benzamide 624 H2N Chi2l ° b_oH N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 0 oxoethyl]-4- [ (2- 342. 3 F fluorophenyl) ethynyl] benzamide 625 H, N Chiral O H NN-OH N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 H 0 oxoethyl]-4- [ (3- 342. 3 fluorophenyl) ethynyl] benzamide F 626 o , N S)-1-(aminomethyl)-2-(hydroxyamino)-2 0 oxoethyl]-4- [ (4- 342. 3 F<} fluorophenyl) ethynyl] benzamide 627 o'y w N- [ (lS)-l- (ammomethyl)-2- (hydroxyamino)-2. oxoethyl]-4- [ (4- 358. 8 chlorophenyl) ethynyllbenzamide 628 p OH Ch, rel oH 4- [ (4- { [ (2S)-2-amino-4- o. methylpentanoyl] amino} phenyl) ethynyl]-N- HzN 467. 5 { (1S, 2R)-2-hydroxy-1- CH3 [(hydroxyamino) carbonyl] propyl} benzamide 629 ou < cyanobutanoyl] aniinolphenyl) ethynyl]-N- HiN Y Y]) P Y) YnY] f o {(lS, 2R)-2-hydroxy-l 464. 5 630 [ (hydroxyamino) carbonyl] propyl} benzamide 630 x-4- [ (4- { [ (2S)-23_ o) L wHW diaminopropanoyl] amino} phenyl) ethynyl]-N-440 5 , N 440. 5 b { (1S, 2R)-2-hydroxy-1- [ (hydroxyammo) carbonyl] propyl} bemzamide 631 Example Structure Name MH+ °Y°u 'N- [4- ( {4- [ ( { (lS, 2R)-2-hydroxy-l- fl < FN ; N-OH [(hydroxyamino) carbonyl] propyl} amino) carbo nyl] phenyl} ethynyl) phenyl] piperidine-3- carboxamide 632 coH ch N- { (lS, 2R)-2-hydroxy-l- 0 1 (hYdrOxYamino) carbonyllpropyll-4- ( (3- 481. 5 <9Nt o [(morpholin-4- "T lr [ (morpholm-4- ylacetyl) ammo] phenyl} ethynyl) benzamide 633 oH Chiral 0 r oH N- {(l S, 2R)-2-hydroxy-1- ° [(hydroxyamino) carbonyl] propyl}-4- (pyrazin- 341. 3 2-ylethynyl) benzamide 634 N 634 N- { (1S 2R)-2-hydroxy-1- OH Chal [ (Y Y) Y] P pY} ( { [ ( { [ p. b. oH h drox amino carbon 1 ro 1-4-4-3- (lH-imidazol-l-519. 6 L1 b o iNoN>NX yl) propyl] amino} acetyl) amino] phenyl} ethynyl 635) benzamide NH H N- ( (IS)-2- (hydroxyaniino)-1-1 [ (1 [3- (lH- Ho"imidazol-1-gg g yl) propyl] amino} acetyl) amino] methyl}-2- oxoethyl)-4- (phenylethynyl) benzamide 636 Chiral O : -r H, OH 4- (f4- [ (f (lS, 2R)-2-hydroxy-l- v [(hydroxyamino) carbonyl] propyl} amino) carbo 383. 4 nyl] phenyl} ethynyl) benzoic acid 637 H3CtOH Chi>31 N-(2-{[4-({4-[({(lsn2R)-2-hydroxy-l- - v i a"8p°H [ (hydroxyamino) carbonyl] propyl} amino) carbo nyl] phenyl} ethynyl) phenyl] amino}-2- b oxoethyl)-1, 3-benzodioxole-4-carboxamide 638 FhC H OH hkal H2N, gN 4-({4-[((2R)-2-{[(2R)-2, 5- diaminopentanoyl] amino}-4- H2Nw NXHt phenylbutanoyl) amino] phenyl} ethynyl)-N- 629. 7 ì (1 S, 2R)-2-hydroxy-1- 639 X3 [(hydroxyamino) carbonyl] propyl} benzamide b<jo FtO H OH Chiral -°"4- [ (4- { [ (2R)-2-amino-4- ", phenylbutanoyl] amino} phenyl) ethynyl]-N- k H {(lS, 2R)-2-hydroxy-1- i [ (hydroxyamino) carbonyl] propyl} benzamide 640 w 1 Example Structure Name MH+ 6c H OH Jf XN 4 [(4 {[(2S) 2amino3 han phenylpropanoyl] amino} phenyl) ethynyl]-N- 501. 6 i X H { (1 S, 2R)-2-hydroxy-1- A [(hydroxyamino) carbonyl] propyl} benzamide 641 w 4- { [4- ( { [ (2- H aniinoethyl) amino] acetyl} amino) phenyl] ethyn. yl)-N- { (lS, 2R)-2-hydroxy-l- H [(hydroxyamino) carbonyl] propyl} benzamide 642 v ? H3 Chlral N N- N-{(1 S)-2-(hydroxyamino)-1-[( {[methyl (l- &N- ("H H methylpiperidin-4- yl) aniino] acetyl) amino) methyl]-2-oxoethyl}-4 (phenylethynyl) benzamide 643 HtCOH mra 4- [ (4- o.-0'°" { [ (cyclobutylammo) acetyl] amino} phenyl) ethy NH_JtN nyl]-N- { (lS, 2R)-2-hydroxy-l- [ (hydroxyamino) carbonyl] propyl} benzamide 644 °Fi°-°H Chiral 4- [ (4- < NH-oH {[(cyclopentylammo) acetyl] amino} phenyl) eth q, 79. 5 a H H ynyl]-N- { (1 S, 2R)-2-hydroxy-1-. [(hydroxyamino) carbonyl] propyl} benzamide 645 oH, CrOH ChlrAl 4~ [(4~ p'li b-°" { [ (cyclohexylamino) acetyl] amino} phenyl) ethy cr nyl]-N-f (lS, 2R)-2-hydroxy-l- 493. 6 646 [(hydroxyamino) carbonyl] propyl} benzamide 646 oHCtOH OH M1. 1 4- [ (4- a'O b °" { [ (cycloheptylamino) acetyl] amino} phenyl) eth (D ynyl]-N- { (lS, 2R)-2-hydroxy-l-""° [(hydroxyamino) carbonyl] propyl} benzamide 647 H p'O b °" { [ (cyclooctylamino) acetyl] amino} phenyl) ethy 521 6 nyl]-N- { (1S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 648 .... N- { (lS, 2R)-2-hydroxy-l- > N-OH [(hydroxyamino) carbonyl] propyl}-4- [ (4- 453. 5 H2C~NHJLHe1-° {[(propylamino) acetyl] amino} phenyl) ethynyl] benzamide 649 Example structure _ Name MH+ 4- [ (4- NC OH °himl O a, _@HN4N-oH {[(hexylamino) acetyl] amino} phenyl) ethynyl]- 495. 6 HCoW N) H N-{(1S, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 650 oH, oh,,.. N- { (lS, 2R)-2-hydroxy-l- p'1rb-°" [ (hydroxyamino) carbonyl] propyl}-4-f [4- (f [ (l- tcHIi H methylethyl) amino] acetyl} amino) phenyl] ethyn yl} benzamide 651 , oH Chlral 4- { [4- ( { [ (1, 1- ; ; i p'1rb-°"dimethylethyl) amino] acetyl} amino) phenyl] eth 467. 5 % C> ( ynyl)-N-I (lS, 2R)-2-hydroxy-l- [(hydroxyamino) carbonyl] propyl} benzamide 652 M, C. OH 0.) -t-\L"' zu b-°" ( { [ethyl (methyl) amino] acetyl} amino) phenyl] et hynyl}-N- { (1S, 2R)-2-hydroxy-1- 453. 5 [(hydroxyamino) carbonyl] propyl} benzamide 653 4-r<f4- H 0 C) H Chl. 1 4- [ (4- H2C ° rigNH_OH {[(diethylamino) acetyl] amino} phenyl) ethynyl] H, CvN tN N-{(lS, 2R)-2-hydroxy-1-6. 5 [ (hydroxyamino) carbonyl] propyl} benzamide 654 H, C^, OH Chlral 4- { [4-( { [(1, 1- dimethylethyl) (Methyl) amino] acetyl} amino) ph 4 -r enyl] ethynyl}-N- { (lS, 2R)-2-hydroxy-l- [ (hydroxyamino) carbonyl] propyl} benzamide 655 °H, C OH-Chirel 4- { [4- b o p °" ( { [cyclohexyl (methyl) amino] acetyl} amino) phe 507 6 nyl] ethynyl}-N- { (1S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 656 oH, CrOH Chlral 4- { [4-( { [biS (1- mol ° °"methylethyl) amino] acetyl} amino) phenyl] ethyn -H-< yl}-N- { (lS, 2R)-2-hydroxy-l-"" [ (hydroxyamino) carbonyl] propyl} benzamide 657 4- { [4- H. O. OH mM' (f [ (cyclohexyhnethyl) amino] aretyl} aniino) phe 507. 6 O rH. JL~ts Jr nyl] ethynyl}-N-{(1S, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 658 Example structure Name MH+ 4-f [4- (f [ (2, 3- dimethyleyclohexyl) aniino] acetyllaniino) phen 521. 6 yl] ethynyl)-N-I (lS, 2R)-2-hydroxy-i- 659 CH, [(hydroxyamino) carbonyl] propyl} benzamide 659 lC OH Chiral 4-f [4- ( ( [ (IR, 2R, 4S)-bicyclo [2. 2. 1] hept-2- "° \ _ r p-b-°"ylamino] acetyl} amino) phenyl] ethynyl}-N- 505. 6 I (lS, 2R)-2-hydroxy-l- [(hydroxyamino) carbonyl] propyl} benzamide 660 4- [ (4- { [ ( { [ (1S, 2R, 5S)-6, 6- FSC OH °himl dimethylbicyclo [3. 1. 1] hept-2- yllmethyllamino) acetyl] amino} phenyl) ethynyl 547. 7 H]-N-{(lS, 2R)-2-hydroxy-1- 661 [(hydroxyamino) carbonyl] propyl} benzamide N- { (lS, 2R)-2-hydroxy-l- H, C., OH CM'-'-'-'-' F F"O-, p-b-°" [ (hydroxyamino) carbonyl] propyl}-4- { [4- ( { [4- 547. 5 (trifluoromethyl) piperidin-l- yl] acetyl} amino) phenyl] ethynyl} benzamide 662 HyN Chiml N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 0U) Y H-OH oxoethyl]-4- (f4- [ ( { [ (2- 504. 5 fluorophenyl) methyl] amino} acetyl) amino] phe nyl} ethynyl) benzamide 663 e., , N- [ (lS)-l- (ammomethyl)-2- (hydroxyamino)-2- -OH oxoethyl]-4- (14- [ ( ( [ (2- chlorophenyl) methyl] amino} acetyl) amino] phe nyl} ethynyl) benzamide 664 HaN q, , N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 _ r ° pb-°"oxoethyl]-4- ( {4- [ ( { [ (2- 500. 6 cH 9, rss-\/ H.. i. t i\, <. n. , i\. 11. oUU. b p methylphenyl) methyl] amino} acetyl) amino] phe nyl} ethynyl) benzamide 665 , N- [ (lS)-l- (anunomethyl)-2- (hydroxyammo)-2- uym-.. oxoethyl]-4- [ (4- { [ (f [2-516. 6 CNJLHv ° (methyloxy) phenyl] methyl} amino) acetyl] amm o} phenyl) ethynyl] benzamide 666 nN ct.,., N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2. F F 0 -OH oxoethyl]-4- [ (4- { [ ('1 [2- (trifluoromethyl) phenyl] methyl} amino) acetyl] amino} phenyl) ethynyl] benzamide 667 Example structure Name MH+ 0) tN Chi. 1 N- [ (IS)-l- (aminomethyl)-2- (hydroxyamino)-2. _ r ; pa-°"oxoethyl]-4- { [4- ( { [ (f 2- g-N-) 4Nlo o [(trifluoromethyl) oxy] phenyl} methyl) amino] ac 570. 5 etyl} amino) phenyl] ethynyl} benzamide 668 HiN p N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 F oxoethyl]-4- (f4- [ ( { [ (3- fluorophenyl) methyl] amino} acetyl) amino] phe nyl} ethynyl) benzamide 669 , , N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 wHNX oxoethyl]-4 ( {4- [ ( { [ (3- cblorophenyl) methyl] amino} acetyl) amino] phe nyl} ethynyl) benzamide 670 N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 oxoethyl]-4- ( {4- [ (f [ (3- 500. 6 methylphenyl) methyl] aniinol acetyl) amino] phe nyl} ethynyl) benzamide 671 H, N Chlr l N-[(1 S)-1-(aminomethyl)-2-(hydroxyamino)-2 'li oxoeth 1-4-4- 0 (methyloxy) phenyl] methyl} amino) acetyl] amin o} phenyl) ethynyl] benzamide 672 , N- [ (lS)-l- (aminomethyl)-2- (hydroxyanuno)-2 = r-pb-°"oxoethyl]-4- [ (4- f [ ( { [3- 554. 5 b (trifluoromethyl) phenyl] methyl} amino) acetyl] amino} phenyl) ethynyl] benzamide 673 N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 0 F H-OH oxoethyl]-4- { [4- ( { [ ( {3_ a-b r [ (trifluoromethyl) oxy] phenyl} methyl) amino] ac etyl} amino) phenyl] ethynyl} benzamide 674 N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 _'pN-°"oxoethyl]-4- (f4- [ ( { [ (4- 504. 5 fluorophenyl) methyl] amino} acetyl) amino] phe nyl} ethynyl) benzamide 675 ", N ,,, a, N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 _NH4K-OH oxoethyl] 4 ( {4 [( {[(4-521 0 chlorophenyl) methyl] amino} acetyl) amino] phe nyl} ethynyl) benzamide 676 Example structure Name MH+ N- [ ( 1 S)-1- (aminomethyl)-2- (hydroxyamino)-2 ow NH OH oxoethyl]-4-({4-[({[(4 500 6 methylphenyl) methyllarmnol acetyl) amino] phe nyl} ethynyl) benzamide 677 N- [ (lS)-l- (aiainomethyl)-2- (hydroxyamino)-2 "iN Chlml oxoethyl]-4- [ (4-1 [ ( [4- 516. 6 (methyloxy) phenyl] methyl} amino) acetyl] amin o} phenyl) ethynyl] benzamide 678 N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 HaN Chlral 0 M-OH oxoethyl]-4- [ (4-1 [ (1 [4- 554. 5 (trifluoromethyl) phenyl] methyl} amino) acetyl] amino} phenyl) ethynyl] benzamide 679 N- [ (lS)-l- (aminomethyl)-2- (hydroxyan-no)-2. oxoethyl]-4- [ (4- { [ ( { [4= (1, 1- H'H'MNaC'° dimethylethyl) phenyl] methyl} amino) acetyljam ino} phenyl) ethynyl] benzamide 680 N, N o. M N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2- .. - oxoethyl]-4- ( {4- [ ( { [ (lR)-l- g b phenylethyl] amino} acetyl) amino] phenyl} ethyn yl) benzamide 681 4N Chtt N-[(lS)-l-(ami-nomethyl)-2-(hydroxyamino)-2 CL NH oxoethyl]-4- ( {4- [ ( { [ (lS)-l- gg ° phenylethyl] amino} acetyl) amino] phenyl} ethyn yl) benzamide 682 Fl, N Ohl N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 0 oxoefllyl]-4-f [4-492. 6 ( { [ (cyclohexylrnethyl) aminolacetyl} aniino) phe nyl] ethynyl} benzamide 683 Hein °hlral N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 , i ° pb-°"oxoethyl]-4- [ (4_ ( [ (cyclobutylaniino) acetyl] amino} phenyl) ethy a { [ ( Y tY) tY]} p Y) Y nyl] benzamide 684 N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 i pb-°"oxoethyl]-4- [ (4- bb { [ (cyclopentylamino) acetyl] amino} phenyl) eth ynyl] benzamide 685 Exam le Structure Name N eh, , N- [ (lS)-l- (aminomethyl)-2- (hydroxyammo)-2 oxoethyl]-4- [ (4- O'b f [ (cyclohexylamino) acetyl] amino} phenyl) ethy 686 nyl] benzamide 686 o"°^ N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 :, _ a ° oxoethyl]-4- [ (4- 492. 6 1 [ (cycloheptylamino) acetyl] amino} phenyl) eth ynyl] benzamide 687 n, N ch. N- [ (lS)-l- (ammomethyl)-2- (hydroxyamino)-2' ow-YL. p-°"oxoethyl]-4- [ (4- f F (cyclooetylaniino) acetyl] amino} phenyl) ethy nyl] benzamide 688 ",",, , N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 _ r p,-b-°"oxoethyl]-4- [ (4- "°.-b-p { [ (ethylamino) acetyl] amino} phenyl) ethynyl] b 424. 5 enzamide 689 HiN qpl N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 rYN"-°"oxoethyl]-4- [ (4-.-,. [ (propylaniino) acetyl] amino} phenyl) ethynyl] '<-'-ti'" { [ (propylammo) acetyl] ammo} phenyl) emynyl] benzamide 690 °,,", N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 oxoethyl]-4- [ (4- 452. 5 HO oNHJLJ O {[(butylamino) acetyl] amino} phenyl) ethynyl] b 452. 5 enzamide 691 N- [ (lS)-l- (aminomethyl)-2- (hydroxyanmio)-2' oxoethyl]-4- [ (4- 480. 6 o Hg 4ou. b c N-pQat' {[(hexylamino) acetyl] amino} phenyl) ethynyl] b enzamide 692 n, N cti ! r. ! N- [ (lS)-l- (aminomethyl)-2- (hydroxyainino)-2- > O oxoethyl]-4 {[4-({[(1 438 5 methylethyl) amino] acetyl} amino) phenyl] ethyn yl} benzamide 693 N Chlral N- [ (1S)-l- (aminomethyl)-2- (hydroxyamino)-2 ° r ! : i a'1'b-°"oxoethyl]-4- { [4- ( { [ (l, l- 452. 5 HOtH tNHe dimethylethyl) amino] acetyl} amino) phenyl] eth ynyl} benzamide 694- Exam le Structure Name MH+ o, ,"a N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 FLN4N-OH oxoethyl] 4 {[4 ( { [ethyl (methyl) amino] acetyl} amino) phenyl] et 438. 5 hynyl} benzamide 695 HaN Chiral N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 ", ° _. NJp / p" °" { [ (diethylamino) acetyl] amino} phenyl) ethynyl] 452. 5 benzamide 696 M, N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 , %. oxoethyl]-4-f [4- ( { [ (11_ dimethylethyl) (methyl) aniinojacetyl) amino) ph enyl] ethynyl} benzamide 697 n, N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 , _, b ° oxoethyl]-4- { [4- ( { [cyclohexyl (moethyl) amino] acetyl} amino) phe nyl] ethynyl} benzamide 698 H, N ct,. N- [ S)-1-(aminomethyl)-2-(hydroxyamino)-2 p, ; _/ a'lra-°"oxoethyl]-4- ( {4- [ ( { [2- (2- fluorophenyl) ethyl] amino} acetyl) amino] pheny 1} ethynyl) benzamide 699 , N o,,., N- [ (lS)-l- (aminomethyl)-2- (hydroxyanmio)-2 ..-yO-rr"oxoethyl]-4- ( {4- [ ( { [2- (3- fluorophenyl) ethyl] amino} acetyl) amino] pheny 700 F 1} ethynyl) benzamide 700 lN N- [ (IS)-l- (aminomethyl)-2- (hydroxyarnino)-2. p J, -/ a'lra-°"oxoethyl]-4- ( {4- [ ( { [2- (4- a fluorophenyl) ethyl] amino} acetyl) amino] pheny 701 1} ethynyl) benzamide 701 n, N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 oxoethyl]-4- ( {4- [ ( { [ (IS, 2R)-2- 512. 6 a henylcyclopropyl] amino acetyl) amino] pheny p Y Y p PY]} h')] p Y 702 1} ethynyl) benzamide 702 H, tH o, ! N- [ (lS)-l- (ammomethyI)-2- (hydroxyammo)-2- . 0''°"oxoethyt]-4- ( {4- [ ( { [ (2, 4- g FaSa difluorophenyl) methyl] amino} acetyl) amtno] ph 2. enyl} ethynyl) benzamide 703 Example structure Name ~ MH+ ", N °",. a, N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 °, -' ; ° p'lo'-°"oxoethyl]-4- ( {4- [ ( { [ (2, 4- 555. 4 dichlorophenyl) methyl] amino} acetyl) amino] p henyl} ethynyl) benzamide 704 H, N , N- [ (lS)-l- (anmiomethyl)-2- (hydroxyamino)-2 0 oxoethyll-4- [ (4- [ ( { [4-fluoro-2- 572. 5 b (trifluoromethyl) phenyl] methyl} amino) acetyl] F F amino} phenyl) ethynyl] benzamide 705 ",",, ro, N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 F oxoethyl]-4- ( {4- [ ( ( [ (2, 5- 522. 5 a difluorophenyl) methyl] amino} acetyl) amino] ph enyl} ethynyl) benzamide 706 H, °",, , N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 ° =, p-°"oxoethyl]-4- ( {4- [ ( { [ (3, 4_ difluorophenyl) methyl] amino} acetyl) amino] ph enyl} ethynyl) benzamide 707 M mM N- [ (lS)-l- (aminomethyI)-2- (hydroxyammo)-2 , .. MV°" oxoethyl]-4- ( {4- [ ( { [ (3, 4- g dichlorophenyl) methyl] amino} acetyl) amino] p henyl} ethynyl) benzamide 708 N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 oxoethyl]-4- ( {4- [ ( { [ (3, 4_ yp y) y]} ty)] p 514. 6 HH c£~NSar dimethylphenyl) methyl] amino} acetyl) amino] p henyl} ethynyl) benzamide 709 N- [ ( 1 S)-1- (aminomethyl)-2- (hydroxyamino)-2 °, , p-b-°" oxoethyl]-4- ( {4- [ ( { [ (3, 5- 522. 5 difluorophenyl) methyl] amino} acetyl) amino] ph enyl} ethynyl) benzamide 710 ","°"""N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 ci M--N-OH oxoethyl]-4- (4- [ (I [ (3, 5- 555. 4 C ; l 0 dichlorophenyl) methyl] amino} acetyl) amino] p henyl} ethynyl) benzamide 711 N- [ (lS)-l- (arninoniethyl)-2- (hydroxyaniino)-2. , -V" oxoethyl]-4- [ (4- { [ ( { [3, 5- bis (trifluoromethyl) phenyl] methyl} amino) acet yl] amino} phenyl) ethynyl] benzamide 712 Exam le Structure Name MH+ mp _ H, N Chlnt N- [ S)-1-(aminomethyl)-2-(hydroxyamino)-2 , r4N-OH oxoethyl]-4-({4-[({[(4 531 5 °'-.-a-xn nitrophenyl) methyl] amino} acetyl) amino] phen yl} ethynyl) benzamide 713 o" N ch ! N- [ (lS)-l- (anmiomethyl)-2- (hydroxyammo)-2' = r : p'lrb-°"oxoethyl]-4- [ (4- { [ (pyridin-2- ylan-jino) acetyl] amino} phenyl) ethynyl] benzam ide ide 714 ide "," "m N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2 oxoethyl]-4- [ (4- f [ (pyridin-3- 473. 5 '" a-b ylamino) acetyl] amino} phenyl) ethynyl] benzam ide 715 o" N N- [ (IS)-l- (aminomethyl)-2- (hydroxyaniino)-2. b'1rb-°"oxoethyl]-4- { [4- ( { [ (2- 490. 5 fluorophenyl) amino] acetyl} amino) phenyl] ethy nyl} benzamide 716 0NN Ch (. 1 N- [ (lS)-l- (aminomethyl)-2- (hydroxyaniino)-2. : r-° bp-°"oxoethyl]-4- { [4- ( { [ (3- 490. 5 , R--N--\/..,... 11 4HU. O fluorophenyl) amino] acetyl} amino) phenyl] ethy nyl} benzamide 717 n, N o. N- [ (lS)-l- (aminomethyl)-2- (hydroxyamuio)-2- AXL o oxoethyl]-4-{[4-({[(4 490 5 b fluorophenyl) amino] acetyl} amino) phenyl] ethy nyl} benzamide 718 o" N ch ! N- [ (lS)-l- (aminomethyl)-2- (hydroxyamuio)-2 oxoethyl]-4- [ (4- f [ (pyridin-4- 473. 5 ylamino) acetyl] amino} phenyl) ethynyl] benzam ide ide 719 H, N ,, , N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 H) ym-.. oxoethyl]-4- ( [4- (I [ (2, 2, 2- 478. 4 0 trifluoroethyl) aniino] acetyl} amino) phenyl] ethy nyl} benzamide 720 N- OH (lS, 2R)-2-hydroxy-1- °FiC OH Chlral [ (hydroxyamino) carbonyl] propyl}-4- [ (4- NJLhr ° {[(pyridin-2 488. 5 "amino) acetyl] amino} phenyl) ethynyl] benzam 721 ide Example Structure Name MH+ N-{(lS, 2R)-2-hydroxy-1- H-'" [ (hydroxyamino) carbonyl] propyl}-4- [ (4- N-<" { [ (Pyridm-3- 488. 5 ylamino) acetyl] amino} phenyl) ethynyl] benzam 722 ide N- { (1S, 2R)-2-hydroxy-1- 4-. C', [ (hydroxyan-jino) carbonyl] propyl}-4- [ (4- =. p 111°fff { [ (pYndin-A.- 488. 5 amino) acetyl] amino} phenyl) ethynyl] benzam 723 ide N- OH (lS, 2R)-2-hydroxy-l- H C OH propg fN if rr- ° i. <--i oob. b phenylpiperazin-l- yl) acetyl] amino} phenyl) ethynyl] benzamide 724 4- { [4- ( { [4- (4-fluorophenyl) piperazin-1- °ro wr cnm SN\NJU N-OH yl] acetyl} amino) phenyl] ethynyl} N- { (1S, 2R)- 574. 6 2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzarnide 725 o''y°"'"4- { [4- ( { [ (1-acetylpipendin-4- YNSH HH o yl) (cyclopropyl) amino] acetyl} amino) phenyl] et ° « PNS hynyl}-N- {(lS, 2R)-2-hydroxy-1- "'° [ (hydroxyamino) carbonyl] propyl} benzamide 726 1% 0 OH Chl. 1 1 [ (butylaniino) acetyl] aniinolphenyl) ethynyl]- 467. 5 a'lra-°" { [ ( tY) tY]} p Y) YnY]-467. 5 N- { (IS, 2R)-2-hydroxy-l- [(hydroxyamino) carbonyl] propyl} benzamide 727 N- { ( 1 S, 2R)-2-hydroxy-1- H, ° OH rnirei N-CH [(hydroxyamino) carbonyl] propyl}-4-({4- [ (f [ (lR)-l- 515. 6 phenylethyl] amino} acetyl) amino] phenyl} ethyn 728 yl) benzamide N-{(lS, 2R)-2-hydroxy-1- n'gN-OH [(hydroxyamino) carbonyl] propyl}-4-({4- 0 515. 6 phenylethyl] amino} acetyl) amino] phenyl} ethyn 729 yl) benzamide °FhC OH Chiral 4- { [4- CS w"4N-OH ({[cyclopropyl (methyl) amino] acetyl} amino) ph 465 5 enyl] ethynyll-N- { (lS, 2R)-2-hydroxy-l- [ (hydroxyamino) carbonyl] propyl} benzamide 730 Example Structure Name MH+ N- { (lS, 2R)-2-hydroxy-l- ", ° °" [ (hydroxyaniino) carbonyl] propyll-4-1 [4- 515. 6 (f [methyl (phenylmethyl) amino] acetyl} amino) phenyl] ethynyl} benzamide 731 ", N Chiral N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 N. M-OH oxoethyl]-4-1 [4- 450. 5 V, N tH ({[cyclopropyl (methyl) amino] acetyl} amino) ph enyl] ethynyl} benzamide 732 H OH Ohlnì 4-[(4-{[(2S)-2- H2N ° N-C4H4N-OH aminopropanoyl] arnino} phenyl) ethynyl]-N-425. 5 CH, {(1 S, 2R)-2-hydroxy-1- 733 [(hydroxyamino) carbonyl] propyl} benzamide 733 o. .., 4- [ (4- { [ (2R)-2- f>HJY aminopropanoyl] arnino} phenyl) ethynyl]-N-425 5 C% { (lS, 2R)-2-hydroxy-l- [ (hydroxyamino) carbonyl] propyl} benzamide 734 | H, CrOH Chinl 4-[(4-{[(2S)-2-amino-3- ° r ; r b'o p °"methylbutanoyl] amino} phenyl) ethynyl]-N- -$H {(lsn2R)-2-hydroxy-l- ", °^°"' [ (hydroxyamino) carbonyl] propyl} benzamide 735 oH, CrOH Chint 4-[(4-{[(2S, 3R)-2-amino-3- -C4HY hy. droxybutanoyl] amino} phenyl) ethynyl]-N- 455. 5 H, N/N {(lS, 2R)-2-hydroxy-1- H, ° °" [ (hydroxyamino) carbonyl] propyl} benzamide 736 H, OH o"°hm (2S)-N- [4- ( {4- [ ( { (1S, 2R)-2-hydroxy-1- N-. H [ (hYdroxyamino) carbonyl] propyl} amino) carbo nyllphenyl} ethynyl) phenyl] pytrolidine-2- carboxamide 737 ", ° °" < XN-OH 4-[(4- {[(2S)-2-amino-3-(lH-imidazol-4- yl) propanoyl] amino} phenyl) ethynyl]-N- f (1 S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 738 MC c ... N- { (lS, 2R)-2-hydroxy-l- O §9HN ; HN-OH [(hydroxyamino) carbonyl] propyl}-4-[(4- H3c-o tHo~d {[(methyloxy) acetyl] amino} phenyl) ethynyl] be nzamide 739 Exam le Structure Name H2N 'm 4- [ (4_ { [ (2S)-2-amino-3- p'O'b-°H methylbutanoyl] amino} phenyl) ethynyl]-N- ", N 438. 5 b [ (1 S)-l- (aminomethyl)-2- (hydroxyamino)-2- n, ccn, oxoethyl] benzamide 740 N- [ (1 S)-1- (aminomethyl)-2- (hydroxyamino)-2 Hy M-OH oxoethyl]-4-f [4- ( { [ (3- phenylpropyl) amino] acetyl) amilio) phenyl] ethy 514. 6 p Y p pY)] tY}) p Y] Y , nyl} benzamide 741 H CHOH Chiral nez rV + NsoH N-{(lS, 2R)-2-hydroxy-1- Aj H O [(hydroxyamino) carbonyl] propyl}-4- (thien-2- 345. 4 C ylethynyl) benzamide s 742 t'H""'4- ( {4- [ ( (2S)-2- { [ (2S)-2, 5- li, 1"'°° N diaminopentanoyl] amino}-3- H, N4N$< phenylpropanoyl) amino] phenyl} ethynyl)-N- 615. 7 "' _ b ° Ff {(lS, 2R)-2-hydroxy-1- 743 [ (hydroxyamino) carbonyl] propyl} benzamide 9H ChM A, Chiral o"3, 4-dihydroxy-N- [ (2S)-3- (hydroxyamino)-3- JM oxo-2- ( { [4- prb'o" (phenylethynyl) phenyl] carbonyl} amino) propyl 460. 5 ] benzamide 744 W C 9.,, ChM 1, 1-ditnethylethyl 3- [ (2- f [ (2S)-3- (hydroxyamino)-3-oxo-2- ( { [4- (phenylethynyl) phenyllcarbonyll amino) propyl 538. 6 ] amino}-2-oxoethyl) amino] propylcarbamate 745 o N Chiral N- [ (1S)-2- (hydroxyamino)-1- ( { [ (4- kl. N 0 methylpiperazin-1-yl) acetyl] amino} methyl)-2- 464. 5 oxoethyl]-4- (phenylethynyl) benzamide 746 746 tNH 4_ {[4-({2-[(2-aminoethyl) amino]-2- b "p°"oxoethyl} oxy) phenyl] ethynyl}-N- { ( S, 2R)-2- q. 55. 5 hydroxy-1- tN fO' O [(hydroxyamino) carbonyl] propyl} benzamide 747 NHz Chiral , I NH oH N-[(1S)-l-(aminomethyl)-2-(hydroxyamino)-2 0 oxoethyl]-4-1 [3- 353. 4 (aminomethyl) phenyl] ethynyl} benzamide 748 Example structure Name MH+ H, Chiral ° H° 1, 1-dimethylethyl (2S)-3- (hydroxyamino)-2- ~ I NOH [({4-[(4-{[2-(hydroxyamino)-2-513 5 oxoethylloxylphenyl) ethynyl] phenyl} carbonyl 0, H, ¢y) amino]-3-oxopropylcarbamate 749 o NH Chiral 0 t H ¢y I NHvOH N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2 pH ° oxoethyl]-4- [ (4- { [2- (hydroxyammo)-2- 413. 4 f oX oxoethyl] oxy} phenyl) ethynyl] benzamide 750 o 750 ,,, 3, 4-dihydroxy-N- (2- { [4- ( {4- [ ( { (lS, 2R)-2- 'OH hydroxy-l- HOA < o [(hydroxyamino) carbonyl] propyl} amino) carbo 547. 5 p. J : J a nyl] phenyl} ethynyl) phenyl] amino}-2- 751 oxoethyl) benzamide KCH OH Chiral 4- (14- [ (I [ (2S)-2, 5- diaminopentanoyl] amino) acetyl) an3ino] phenyl 525. 6 HrN NsJI h, ¢r} ethynyl)-N-{(lS, 2R)-2-hydroxy-1- ° O [ (hydroxyamino) carbonyl] propyl} benzamide 752 uH ChM 4- [ (4- { [ (2- HN H OH aminoethyl) amino] carbonyl} phenyl) ethynyl]- 425. 5 N~NX N- {(1 S, 2R)-2-hydroxy-1- H2 [(hydroxyamino) carbonyl] propyl} benzamide 0 753 0 NH. Chlral N- [ (1S)-1- [ ( { [ (3- i pbOH aminopropyl) amino] acetyl} amino) methyl]-2- q, 38. 5 < (hydroxyamino)-2-oxoethyl]-4- (phenylethynyl) benzamide 754 Chfral , 3- ( {4- [ ( { (lS, 2R)-2-hydroxy-l- [ (hydroxyamino) carbonyl] propyl} amino) carbo 383. 4 HO<'nyl] phenyl} ethynyl) benzoic acid 755 H, O Chal 4-1 [4- (1 [ (3- XhisOH aminopropyl) amino] acetyl} amino) phenyl] ethy nyl}-N- { (lS, 2R)-2-hydroxy-l- 1 (hydroxyan) ino) carbonyl] propyl} benzamide 756 NH Chiral 0 t H I°I °"N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 ¢N< oxoethyl]-4-(pyrazin-2-ylethynyl) benzamide 757 CN 'Example structure Name MH+ Chiral 4- ( {3_ [ (4- 0 aniinobutanoyl) an-iino] phenyl) ediynyl)-N- 424. 5 H, N (N) Y [(1S)-1-(aminomethyl)-2-(hydroxyamino)-2- oxoethyl] benzamide 758 NH, Chkal chM N- [ (lS)-l- (ammomethyI)-2- (hydroxyamino)-2- vh o oxoethyl]-4-[(4-{[(2S)-2, 5-453 5 diaminopentanoyl] amino} phenyl) ethynyl] benz HzNN 759 NH, amide 759 NH2 Chiral HN O I OH 4- (f 2- [ (aminoacetyl) amino] phenyl) ethynyl)-N. O NH/i o [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2- 396. 4 oxoethyl] benzamide 760 NH Chiral I+HNg OH OH S)-l-(aminomethyl)-2-(hydroxyamino)-2 JWt oxoethyl]-4-({4-[2-(ethylamino)-2-409. 5 oxoethyl] phenyl} ethynyl) benzamide 761 NHL, Chiral 9 Jk 4- ( {4- [ (aminoacetyl) anmio]-3- Hoei HN o methylphenyl} ethynyl)-N-[(lS)-l-410 4 410. 4 (aminomethyl)-2- (hydroxyamino)-2- oxoethyl] benzamide 762 NChiral ij4HN NOH 4-( {4-[(aminoacetyl) amino] phenyl} ethynyl)-N g [(1 S)-1-(aminomethyl)-2-(hydroxyamino)-2-414. 4 H2NAN JS'oxo ethyl]-3-fluorobenzamide 763 , Chiral N_ [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 oxoethyl]-4-f [4- 435. 5 N% NJk Jr ({[(cyanomethyl) amino] acetyl} amino) phenyl] ethynyl} benzamide 764 HjCOH Chra ! [4- ( {4- [ ( { (1S, 2R)-2-hydroxy-1_ » ° [(hydroxyamino) carbonyl] propyl} amino) carbo 397. 4 nyl] phenyl} ethynyl) phenyl] acetic acid 765 tt, OH OH Clhiral "-on 4-ammo-2- ( { [4- ( {4- [ ( { (lS, 2R)-2-hydroxy-l- wi [ (hydroxyamino) carbonyl] propyl} amino) carbo H, N nyl] phenyl} ethynyl) phenyl] carbonyl} amino)-4 497. 5 COHO oxobutanoic acid 766 Example structure Name MH+ ° cx'p, °"°'a 4-amino-2- [ ( { [4- ( {4- [ ( { (1S, 2R)-2-hydroxy-1- 'p. ° [ (hydroxyamino) carbonyl] propyl} amino) carbo '527. 5 H, NNno) nyl] phenyl} ethynyl) phenyl] oxy} acetyl) amino] ° OH 4-oxobutanoic acid 767 °N Chiral o N N-((1 S)-2-(hydroxyamino)-1- { [(morpholin-4- °"ylacetyl) amixo] methyl}-2-oxoethyl)-4- 451. 5 e (phenylethynyl) benzamide 768 v t4StOHChlral NH OH N-[(lS)-1-[({[(2, 3- "dihydroxypropyl) thio] acetyl} amino) methyl]-2- q. 72. 5 ° (hydroxyamino)-2-oxoethyl]-4- (phenylethynyl) benzamide 769 f Chiral NN°'cH methyl (2S)-3-amino-2-({[4- H 0 (phenylethynyl) phenyl] carbonyl} amino) propa 323. 4 i noate 770 ~S, Chìral N- { (1S)-2- (hydroxyamino)-2-oxo-1- [ ( { [ (2- H I HN phenylethyl) amino] acetyl} amino) methyl] ethyl 485. 6 }-4- (phenylethynyl) benzamide fr 771 H, CtN 4-[(4-{2-[(2-aminoethyl) amino]-2- oxoethyl) phenyl) ethynyl]-N- { S, 2R)-2-439. 5 hydroxy-1- HiNN ( (hydroxyamino) carbonyl] propyl} benzamide 772 c-4- [ (4- { [ (6- Hha sOH aminohexyl) am'ino] carbonyl} phenyl) ethynyl]- N- { (1S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 773 SC OH Chl. 1 4- [4- (4- pp-°" { ( (ethylamino) acetyl] amino} phenyl) buta-1, 3- HCsNstHe diynyl] N {(1 S, 2R) 2hydroxy-1. [(hydroxyamino) carbonyl] propyl} benzamide 774 NO cM 4- [4- (4- { [ (cyclopropylamino) acetyl] amino} phenyl) but 475. 5 -0 ° a-l, 3-diynyl]-N- { (lS, 2R)-2-hycb-oxy-l- [(hydroxyamino) carbonyl] propyl} benzamide 775 Example Structure Name MH+ mp c o. ,., N- { (lS, 2R)-2-hydroxy-l- wht rs-oH [(hydroxyamino) carbonyl] propyl}-4- (4- {4- nNAhv (piperidin-1-ylacetyl) amino] phenyllbuta-1, 3- p- [ (P P Y t3')] p Y} diynyl) benzamide 776 ItC m,.. N- { (lS, 2R)-2-hydroxy-l- 0 [ (hydroxyan-iino) carbonyl] propyl}-4- [4- (4- { [ (phenylamino) acetyl] amino} phenyl) buta-1, 3 511. 5 diynyl] benzamide 777 H, OH .. N- { (lS, 2R)-2-hydroxy-l- p,-b-°" [ (hydroxyamino) carbonyl] propyl}-4- {4- [4- O HsL < ° ({[(phenylmethyl) arnmo] acetyl} amino) phenyl] 525. 6 buta-1, 3-diynyl} benzamide 778 o a° NHz Chiral v J_NV N-{(lS, 2R)-2-amino-1- o [ (hYdroxyamino) carbonyl] propyl}-4'-ethyl-1, 1' 342. 4 biphenyl-4-carboxamide 779 °", ° °" 4- [ (4_ °'= i p-p-°" { [ (dimethylamino) acetyl] amino} phenyl) ethyny H, C'NJQHNgsJ 1]-N- {(1 S, 2R)-2-hydroxy-1- 780 [(hydroxyamino) carbonyl] propyl} benzamide 780 c. .. N- { (lS, 2R)-2-hydroxy-l- -Nl ; o [ (hYdroxyaniino) carbonyllpropyll-4- (14- 465. 5 465. 5 \J) JL-<y [ (pyn-olidm-1- ylacetyl) amino] phenyl} ethynyl) benzamide 781 N- OH (lS, 2R)-2-hydroxy-l- ", ° °" 4N-OH [(hydroxyamino) carbonyl] propyl)-4- [ (4- 481. 6 C% NHAhNw {[(pentylamino) acetyl] amino} phenyl) ethynyl] benzamide 782 N-{(lS, 2R)-2-hydroxy-1- n gHN-OH [(hydroxyamino) carbonyl] propyl}-4- { [4- pp I ; i p'l'p-°" ,, ° ( { [ (thien-2- 507. 6 yhnethyl) amino] acetyl} amino) phenyl] ethynyl} 783 benzamide toj ", °", " 4- { [4-C { [ (iH-benzimidazol-2- ,, p,-p-°"ylmethyl) amino] acetyl} amino) phenyl] ethynyl N- { (IS, 2R)-2-hydroxy-l- 541. 6 [ (hydroxyamino) carbonyl] propyl} benzamide 784 Example structure Name MH+ 4- { [4-( { [(1-benzothien-3- °", ° °" # a-°"yhnethyl) amino] acetyl} amino) phenyl] ethynyl} ' 557. 6 -'° N- { (lS, 2R)-2-hydroxy-l- -S [(hydroxyamino) carbonyl] propyl} benzamide 785 c. . 4- (4- {4- [ ( { [ (2- 0 fluorophenyl) methyl] amino} acetyl) amino] phe 543 6 nyl) buta-1, 3-diynyl)-N-I (lS, 2R)-2-hydroxy-l- [(hydroxyamino) carbonyl] propyl} benzarnide 786 4- (4- {4- [ ( { [ (3_ fluorophenyl) methyl] amino} acetyl) amino] phe FJO NJitHNv nyl} buta-1, 3-diynyl)-N- {(lS, 2R)-2-hydroxy-1- [(hydroxyarnino) carbonyl] propyl} benzamide 787 H C W Chi. 1 4- (4-14- [ (f [ (4- ,, r pp-°"fluorophenyl) methyl] amino} acetyl) amino] phe 543. 6 . uJp' nyl} buta-1, 3-diynyl)-N- { (1S, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 788 N- { (1S, 2R)-2-hydroxy-1- ", ° oH chlmi [ (hydroxyamino) carbonyl] propyl}-4- (4- {4- pd-°" methylphenyl) methyl] amino} acetyl) amino] phe 789 nyl} buta-1, 3-diynyl) benzamide N-{(lS, 2R)-2-hydroxy-1- A Cr N-OH [(hydroxyamino) carbonyl] propyl} 4 (4 {4 ap. [ ( { [ (3- 539. 6 methylphenyl) methyl] amino} acetyl) amino] phe 790 nyl} buta-l, 3-diynyl) benzamide N-{(lS, 2R)-2-hydroxy-1- '> N-OH [(hydroxyamino) carbonyl] propyl}-4-(4- {4- yg-H SQNJL eH o [({[(539. 6 methylphenyl) methyl] amino} acetyl) amino] phe 791 nyl} buta-1, 3-diynyl) benzamide a N- {(1 S, 2R)-2-hydroxy-1- N-OH [(hydroxyamino) carbonyl] propyl}-4-{4-[4- (f [ (pyridin-2- 526. 6 H ylmethyl) amino] acetyl} amino) phenyl] buta-l, 3 792 diynyl} benzamide N- { S, 2R)-2-hydroxy-1- out gN OH [(hydroxyamino) carbonyl] propyl}-4- {4- [4- ol (f [ (pyridin-3- 526. 6 yhnethyl) amino] acetyl} amino) phenyl] buta-1, 3 793 diynyl} benzamide Example structure Name MH+ N-{(lS, 2R)-2-hydroxy-1- "° °"°"° [ (hydroxyamino) carbonyl] propyl}-4- {4- [4- No ( { [ (pyridin-4- 526. 6 methyl) amino] acetyl} amino) phenyl] buta-1, 3 794 diynyl} benzamide N-{(lS, 2R)-2-hydroxy-1- 2vC4HN OHChlMl [(hydroxyammo) carbonyl] propyl}-4- [4- (4- f [ (1 [2- 555. 6 (methyloxy) phenyl] methyl} amino) acetyl] amm 795 o} phenyl) buta-l, 3-diynyl] benzamide N- { (lS, 2R)-2-hydroxy-1- H° °H °ninl H4N-OH [(hydroxyamino) carbonyl] propyl}-4- [4- (4- , [ ( { [3- 555. 6 °H, (methyloxy) phenyl] methyl} amino) acetyl] amm 796 o} phenyl) buta-1, 3-diynyl] benzamide N- { ( 1 S, 2R)-2-hydroxy-1- gH, O gN OH [(hydroxyamino) carbonyl] propyl}-4- [4- (4- 'lrd_, °ppp ° {f ( {f4- 555. 6 (methyloxy) phenyl] methyl} amino) acetyl] amm 797 o} phenyl) buta-1, 3-diynyl] benzamide ti-'"'4- {4- [4- ( { [ (2- H O wahY fluorophenyl) amino] acetyl} amino) phenyl] buta aF a 1, 3-diynyl}-N- { (1S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 798 °H, ° °HH , . 4- {4- [4- ( { [ (3- N-OH Ngt vH o fluorophenyl) amino] acetyl} amino) phenyl] buta 529 5 1, 3-diynyl}-N- { S, 2R)-2-hydroxy-1- F [(hydroxyamino) carbonyl] propyl} benzamide 799 C c. .. 4- {4- [4- ( { [ (4- O-OH fluorophenyl) amino] acetyllaniino) phenyl] buta a 1, 3-diynyl}-N- { (lS, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 800 N-{(lS, 2R)-2-hydroxy-1- .-yH-"" [ (hydroxyamino) carbonyl] propyl}-4- [4- (4- C,-Y. f [ (pyridin-2- 512. 5 ylamino) acetyl] amino} phenyl) buta-l, 3- 801 diynyl] benzamide oU1 N-{(lS, 2R)-2-hydroxy-1- jrv'" [ (hydroxyamiiio) carboiiyl] propyl}-4- [4- (4- \ p, = ° { [ (pyridin-3- 512. 5 ylamino) acetyl] amino} phenyl) buta-1, 3- 802 diynyl] benzamide Exa le Structure Name MH+ mp N- { ( 1 S, 2R)-2-hydroxy-1- p. b-°" [ (hydroxyamino) carbonyl] propyl}-4- [4- (4- Hs ° {[(pyridin-4-512. 5 ylamino) acetyl] amino} phenyl) buta-1, 3- 803 diynyl] benzamide oUj 6C OH Chl. 1 4- [4- (4- ul M-OH [ (cyclobutylaniino) acetyl] amino} phenyl) buta -r ° l, 3-diynyl]-N- { (lS, 2R)-2-hydroxy-l- [(hydroxyamino) carbonyl] propyl} benzamide 804 H, COH Ch !,.) 4- [4- (4- _<4N-OH {[(cyclopentylamino) acetyl] amino} phenyl) but 503. 6 a-l, 3-diynyl]-N- { (lS, 2R)-2-hydroxy-1- d [(hydroxyamino) carbonyl] propyl} benzamide 805 o, cM,., 4- [4- (4- O H hHs {[(cyclohexylamtno) acetyl] amino} phenyl) buta O HNJah 1, 3-diynyl]-N- {(1 S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 806 M-oH m,., 4- [4- (4- N-OH °(cycloheptylaxnino) acetyl] amino} phenyl) but NH-L a-l, 3-diynyl]-N-{(1 S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 807 o-c en c... N- { (lS, 2R)-2-hydroxy-l- r p,-a-°" [ (hydroxyamino) carbonyl] propyl}-4- [4- (4- H c { [ (methylanmio) acetyl] anuno} phenyl) buta-l, 3 diynyl] benzamide 808 .. . N- { (lS, 2R)-2-hydroxy-l- p,-a-°" [ (hydroxyamino) carbonyl] propyl}-4- [4- (4- H, { [ (propylamino) acetyl] ammo} phenyl) buta-l, 3 diynyl] benzamide 809 H C . 4- [4- (4- _gN4N-°H { [(butylamino) acetyl] amino} phenyl) buta-1, 3-491 6 H, Cs^, Nn-¢ ; diynyl]-N- {(1 S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 810 .... N- { (lS, 2R)-2-hydroxy-l- 1 (hYdrOxYaminO) carbonyllpropyl)-4- [4- (4- "°-. d. Jp-0' : H, CwNkNv { [(pentylamino) acetyl] amtno} phenyl) buta-l, 3- diynyl] benzamide 811 Example Structure Name MH+ 4- [4- (4- N, c o11 chlni '4NOH {[(hexylamino) acetyl] amino} phenyl) buta-1, 3- ° diynyl]-N- { (1S, 2R)-2-hydroxy-1- 519. 6 [(hydroxyamino) carbonyl] propyl} benzamide 812 H, OH cht. 1 4- {4 hW ( { [ethyl (methyl) amino] acetyl} amino) phenyl] b 477. 5 S < uta-1, 3-diynyl}-N-{(lS, 2R)-2-hydroxy-1- laCN [(hydroxyamino) carbonyl] propyl} benzamide 813 N- { ( 1 S, 2R)-2-hydroxy-1- 0-1 H-OH [ (hydroxyamino) carbonyl] propyl)-4-14- [4- (11 (1- 477. 5 methylethyl) amino] acetyl} amino) phenyl] buta- 814 1, 3-diynyl} benzamide N- { (lS, 2R)-2-hydroxy-1- 0 [ (hydroxyamino) carbonyl] propyl}-4- {4- [4- (1 [ (2- 491. 6 methylpropyl) amino] acetyl} amino) phenyl] but 815 a-1, 3-diynyl} benzamide N-{(lS, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl}-4-14- [4- b'1'b oH F-/ (1 [ (2, 2, 2- 517. 5 trifluoroethyl) amino] acetyl} amino) phenyl] but 816 a-1, 3-diynyl} benzamide olb 4- {4- [4- ( { [ (2- qx,-d-°"hydroxyethyl) amino] acetyl} amino) phenyl] buta HO~NJL 1, 3-diynyl}-N- {(1 S, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 817 N-{(lS, 2R)-2-hydroxy-1- ", ° °"° [ (hydroxyamino) carbonyl] propyl}-4- (4- {4- N 5 H, -°pp'° [ ( { [2- 493. 5 (methyloxy) ethyl] amino} acetyl) amino] phenyl} 818 buta-1, 3-diynyl) benzamide olo H, C- oN Chlnl 4- (4- {4- [ ( { [2- (diinethylarriino) ethyl] amino} acetyl) amino] ph 506. 6 enyl} buta-1, 3-diynyl)-N-I (IS, 2R)-2-hydroxy- 506. 6 1- [ (hydroxyamino) carbonyl] propyl} benzamide 819 H, ; Cht. 1 4 _>-tNXN-°"cyanoethyl) amino] acetyl} amino) phenyl] buta-488 5 Nbp'' 1, 3-diynyl}-N- { (1S, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 820 Example Structure Name MH+ _ H, C OH ChlrÇl N-{(lS, 2R)-2-hydroxy-1- wh4N OH [(hydroxyamino) carbonyl] propyl}-4-(4-{4- [ (pyrrolidin- I-ylacetyl) aniino] phenyll buta-1, 3 diynyl) benzamide 821 H, O on .., 4- (4- {4- [ (azepan-l- _@ WHN oH ylacetyl) amino] phenyl} buta-1, 3-diynyl)-N-517 6 N¢r {(1 S, 2R) 2hydroxy1 [(hydroxyamino) carbonyl] propyl} benzamide 822 N-{(lS, 2R)-2-hydroxy-1- *)"°H "'hydroxyammo) carbonyl] propyl}-4- [4- (4- { [ (4 methylpiperazin-l-518. 6 yl) acetyl] amino} phenyl) buta-1, 3- 823 diynyllbenzamide 82j H, OH az l N-{(lS, 2R)-2-hydroxy-1- . f'HTf"'°" [ (hydroxyamino) carbonyl] propyl}-4- (4- {4- ONJiLhr [(morpholin-4-ylacetyl) amino] phenyl} buta-1, 3 diynyl) benzamide 824 H, OH OH Ct ! 4- {4- [4- ° , r pa °" ( { [cyclohexyl (methyl) amino] acetyl} amino) phe 531 6 ac nyl] buta-1, 3-diynyll-N-I (lS, 2R)-2-hydroxy-l- [(hydroxyamino) carbonyl] propyl} benzamide 825 N- {(1 S, 2R)-2-hydroxy-1- ° °H v4N-OH [(hydroxyamino) carbonyl] propyl}-4- (4- {4- 0-0" [ ( { [ (IR)-1- 539. 6 phenylethyl] amino} acetyl) amino] phenyl} buta- 826 1, 3-diynyl) benzamide 826 N-{(lS, 2R)-2-hydroxy-1- H, ° °H , [ (Y) Y] p PY} ( { ° NgN-OH [(hydroxyamino) carbonyl] propyl}-4-(4-{4- --'Wp ° [ ( { [ (1S)-1- 539. 6 H, phenylethyl] amino} acetyl) amino] phenyl} buta- 827 1, 3-diynyl) benzamide 827 N- {(1 S, 2R)-2-hydroxy-1- H-cH""' [ (hydroxyammo) carbonyl] propyl}-4- {4- [4- Jwb-°H r llllp ( { [ (2- 539. 6 phenylethyl) amino] acetyl} amino) phenyl] buta- 828 1, 3-diynyl} benzamide 828 c. ... N- { (lS, 2R)-2-hydroxy-l- r p,-p-°" [ (hydroxyamino) carbonyl] propyl}-4- (4- {4- NANJLhv [(lH-imidazol-1-ylacetyl) amino] phenyl} buta- p 1, 3-diynyl) benzamide 829 Example structure Name MH+ , c o. ... 4- {4- [4- ( { [ (lR, 2R, 4S)-bicyclo [2. 2. 1] hept-2- "/ g _w"4N-OH ylamino] acetyl} amino) phenyl] buta-1, 3-529 vNJLHNv diynyl}-N- {(lS, 2R)-2-hydroxy-1-. 6 [ (hydroxyamino) carbonyl] propyl} benzamide 830 H, {4- [4- N-OH ( { [ (cyclohexylmethyl) amino] acetyl} amino) phe O<NAN-nyl] buta-1, 3-diynyl}-N- {(1 S, 2R)-2-hydroxy-1- 831 [(hydroxyamino) carbonyl] propyl} benzamide 831 NH Chiral °_ , , °H N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 gH iNQ oxoethyl]-4'-ethyl-2-fluoro-1, 1'-biphenyl-4-346. 4 carboxamide 832 832 H'° OH 4- 4- [ (aminoacetyl) amino] phenyl} ethynyl)-N N Flo f (I S, 2R)-2-hydroxy- 1-441. 5 ti 441. 5 H2NJ [ (hydroxyarnino) carbonyl] propyl}-3- (methyloxy) benzamide 833 H3C H OH Chiral 0 4'-ethyl-N-I (IS, 2R)-2-hydroxy-l- 0 HN (hydroxyamino) carbonyl] propyl}-2- 373. 4 1-1HCIO (methyloxy)-1, I'-biphenyl-4-carboxamide H, cl 834 H C Li OH Chiral O H vHNX OH N-{(lS, 2R)-2-hydroxy-1- AJ [(hydroxyamino) carbonyl] propyl}-3-369. 4 (methyloxy)-4- (phenyletliynyl) benzamide /3 835 H, C, OH Chirac M. 4- [ (4-ethylphenyl) e<hynyl]-N- { (lS, 2R)-2- hydroxy-1-367. 4 H3CJA [(hydroxyamino) carbonyl] propyl} benzamide 836 836 H, C H OH Chiral p-b. OH N- { (1S, 2R)-2-hydroxy-1- H [(hydroxyamino) carbonyl] propyl}-4-[(4-355. 4 hydroxyphenyl) ethynyl] benzamide HO' 837 Chiral 0-11-S-1OH f NH ° 2-[(2- {[(2S)-3-(hydroxyamino)-3-oxo-2-( {[4- OH (phenylethynyl) phenyl] carbonyl} amino) propyl 470. 5 0-2-oxoethyl) thio] propanoic acid ] aniinol 838 Example structure Name MH+ Chiral goH2 4-amino-2-[(2-{[(2S)-3-(hydroxyamino)-3-oxo tH o 2-( { [4~ (phenylethynyl) phenyl] carbonyl} amino) propyl 496. 5 ] amino}-2-oxoethyl) amino]-4-oxobutanoic 839 acid Chlral 1, 1-dimethylethyl 4-amino-2- [ (2- { [ (2S)-3- NH"o c (hydroxyammo)-3-oxo-2- ( { [4- ° o" (phenylethynyl) phenyl] carbonyl} amino) propyl 840 amino}-2-oxoethyl) amino]-4-oxobutanoate , OH Chiral PH OUra ! 0 1NOH 2, 6-dihydroxy-N-[(2S)-3-(hydroxyamino)-3- O N oxo-2- ( { [4- (phenylethynyl) phenyl] carbonyl} amino) propyl 841] pyridine-4-carboxamide 841 NHa Chiral 0 I<HN N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 0 oxoethyl]-4- [ (4- 339. 4 aminophenyl) ethynyl] benzamide H2N 842 NH Chira) ON I NsOH N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 S oxoethyl]-4-[(4-352. 4 ethylphenyl) ethynyl] benzamide 843 NHz Chiral 0 OH N- [ (lS)-I- (aniffiomethyl)-2- (hydroxyamino)-2 o oxoethyl]-4- [ (4-ethylphenyl) ethynyl]-3- 370. 4 fluorobenzanude 844 Ng Chiraì N- [ S)-1-(aminomethyl)-2-(hydroxyamino)-2 a ° °"oxoethyl]-4- ( {4- [ (3_ aminopropanoyl) amino] phenyl} ethynyl) benza y P p Y)] p Y} YnY) mide 845 giN N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2 b ° o"oxoethyl]-4- [ (4- 424. 5 gCD [(dimethylamino) acetyl] amino} phenyl) ethyny "'° b 1] benzamide 846 NHi Chkal 4_ ( {4_ [ (4_ b ° °"aminobutanoyl) amino] phenyl} ethynyl)-N- [ (IS)-l- (aminomethyl)-2- (hydroxyamino)-2- oxoethyl] benzamide 847 Example structure Name MH+ H Chiral N N- {(I S)-2-(hydroxyamino)-1-[( {[2- b. °H (methyloxy) phenyl] methyl} amino) methyl]-2- 444. 5 zozo oxoethyl}-4- (phenylethynyl) benzamide fT 848 tlz Chìral N°H= N9=CH2 N-[(1 S)-1-[(diprop-2-enylamino) methyl]-2- (hydroxyamino)-2-oxoethyl]-4-404. 5 ° (phenylethynyl) benzamide Y 9cHzchìral Q'CHchtra) N- [ (lS)-2- (hydroxyaniino)-J- ( { [ (f [2- b, °H (methyloxy) phenyl] methyl} amino) acetyl] amin 501. 6 o o} methyl)-2-oxoethyl]-4- (phenylethynyl) benzamide Chiral ChM ogJ NH0 N- ( (lS)-2- (hydroxyamino)-i-f [ (1 [2- (methyloxy) phenyl] thio} acetyl) amino] methyl} 504. 6 w 2-oxoethyl)-4- (phenylethynyl) benzamide 851 851' F6c NH Chiral 0'2 (2S, 3R)-3-amino-2- (f [4- o (phenylethynyl) phenyl] carbonyl} amino) butano 323. 4 852 ic acid 852 N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 i pp-"oxoethyl]-4- [4- (4- 448. 5 cA vNs4N-oH {[(inethylamino) acetyl] amino} phenyl) buta- 853 1, 3-diynyl] benzamide 853 Nu a,, , N- [ (lS)-l- (anunomethyl)-2- (hydroxyamino)-2 oxoethyl]-4- [4- (4- 448. 5 H, OJLH < H4tHs ow {[(ethylamino) acetyl] amino} phenyl) buta-l, 3- diynyl] benzamide 854 N- [ (1S)-1- (aminometlryl)-2- (hydroxyamino)-2 i p'1o b-o"oxoethyl]-4- [4- (4- b. . c clo ro la) ty]} p y) 460. 5 o-p { [ ( y p py mino ace 1 amino hen 1 but a-1, 3-diynyl] benzamide 855 , N , ra N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 p'1rb-"oxoethyl]-4- (4- {4- [ (piperidin-1- OH-0" ° ylacetyl) amino] phenyl} buta-l, 3- diynyl) benzamide 856 Example structure Name MH+ n, N Chial N- S)-l-(aminomethyl)-2-(hydroxyamino)-2 p_o, oxoethyl]-4- [4- (4- i b"'a- { [ (phenylamino) acetyl] amino} phenyl) buta-l, 3 496. 5 diynyl] benzamide 857 ","N C,, , N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 vaHk oxoethyl]-4 {4 [4 51 (f [ (phenyhnethyl) amino] acetyl} amino) phenyl] 0. 6 buta-1, 3-diynyl} benzamide 858 HiN Chiral 4 N-OH N- [ S)-1-(aminomethyl)-2-(hydroxyamino)-2 0 oxoethyl]-4- [4- (4-aniinophenyl) buta-1, 3- 363. 4 H2N diynyl] benzamide 859 N- { (lS, 2R)-2-hydroxy-l- °H 'm [ (hydroxyamino) carbonyl] propyl}-4- [ (4- Ic 0 f [ (pyrazin-2- 489. 5 NseN ylamino) acetyl] amino} phenyl) ethynyl] benzam 860 ide N- { (lS, 2R)-2-hydroxy-l- [ (hydroxyan-no) carbonyl] propyl}-4- [ (4- { [ (4- phenylpiperidin-l- yl) acetyl] amino} phenyl) ethynyl] benzamide 861 4-f [4- (f [4- (2-fluorophenyl) piperazin-1- H OH inl p--a-°H yl] acetyl} amino) phenyl] ethynyl}-N- { (1S, 2R)- 2-hydroxy-l-574. 6 [(hydroxyamino) carbonyl] propyl} benzamide 862 H. c on c., 4- { [4- ( { [ (lS, 4R)-bicyclo [2. 2. 1] hept-2- H ylamino] acetyl} amino) phenyl] ethynyl}-N- { (1 S, 2R)-2-hydroxy-l- [ (hydroxyamino) carbonyl] propyl} benzamide 863 N- {(1 S, 2R)-2-hydroxy-1- H, Ct, OH ChlrAl [hydroxyamino) carbonyl] propyl}-4- ( {4- lC Cit 0 [ ( { [ (IS, 2S, 3S, 5R)-2, 6, 6- 547. 7 trimethylbicyclo [3. 1. 1] hept-3- yl] amino} acetyl) amino] phenyl} ethynyl) benza 864 mide o,, N-I (IS, 2R)-2-hydroxy-l- YS-C<H~-OH [(hydroxyamino) carbonyl] propyl}-4-{[4- A H ({[(tricyclo [3. 3. 1. 1-3, 7~] dec1 559-7 Ht, H ylmethyl) amino] acetyl} amino) phenyl] ethynyl} 865 | benzamide ExampleStructureNameMH+ c on c...., N- { (lS, 2R)-2-hydroxy-l- < N OH [(hydroxyamino) carbonyl] propyl}-4-{[4-({[(4 1 507 6 methylcyclohexyl) aminolacetyllamino) phenyl "'°] ethynyl} benzamide 866 N- { S, 2R)-2-hydroxy-1- °''Y°"t) °""' [ (hydroxyamino) carbonyl] propyl}-4- { [4- p''b-o" F, ibJp ;-_ ° ( { [ (2, 2, 2- 493. 5 trifluoroethyl) amino] acetyl} amino) phenyl] ethy 867 nyl} benzamide ob/ a-% C OH H-OH Cht. 1 4- ( {4- [ ( { [2- (2- fluorophenyl) ethyl] amino} acetyl) amino] pheny I} ethynyl)-N-f (lS, 2R)-2-hydroxy-l- [(hydroxyamino) carbonyl] propyl} benzamide 868 OH 4- ( {4- [ ( { [2- (3- 9 S4N-OH fluorophenyl) ethyl] amino} acetyl) amino] pheny F_O-Ilethynyl)-N- { (lS, 2R)-2-hydroxy-l- 533. 6 [(hydroxyamino) carbonyl] propyl} benzamide 869 . H.... 4- ( {4- [ ( { [2- (4- H fluorophenyl) ethyl] amino} acetyl) amino] pheny a 1} ethynyl)-N- { (1S, 2R)-2-hydroxy-l- [ (hydroxyamino) carbonyl] propyl} benzamide 870 N- { (1 S, 2R)-2-hydroxy-1- °"'°p-°"°'"° [ (hydroxyamino) carbonyl] propyl}-4- ( {4- v H9tH O vH [({[(1S, 2R) 2 527. 6 W phenylcyclopropyl] amino} acetyl) amino] pheny 871 l} ethynyl) benzamide Of1 oH, ch... N- { (lS, 2R)-2-hydioxy-l- pa-°" [ (hydroxyamino) carbonyl] propyl)-4- ( {4- [ (f [ (2 515. 6 tNHNw methylphenyl) methylamino} acetyl) amino] phe nyl} ethynyl) benzamide 872 H. coH cM... N- { (lS, 2R)-2-hydioxy-l- b'o p °" [ (hydroxyamino) carbonyl] propyl}-4- [ (4- { [ ( { [2 569. 5 Fr HN (trifluoromethyl) phenyl] methyl} amino) acety, l] F-F F amino} phenyl) ethynyl] benzamide 873 N- { (lS, 2R)-2-hydroxy-l- H, C, OH Ch. ra. ''-' <--S-..-IH-oH [ (hydroxyanmio) carbonyl] propyl}-4- { [4- ( ( [ ( {2- 585. 5 O>FF [(trifluoromethyl) oxy] phenyl} methyl) amino] ac 874 etyl} amino) phenyl] ethynyl} benzamide Example Structure Name MH+ 4- ( {4- [ ( { [ (4- H. C. OH Ct. M' L'. tL\ 0 chlorophenyl) methyl] amino} acetyl) amino] phe nyll ethynyl)-N-f (I S, 2R)-2-hydroxy- I- [(hydroxyamino) carbonyl] propyl} benzamide 875 H, o.... N- { (lS, 2R)-2-hydroxy-l- px,-b-°H [ (hydroxyamino) carbonyl] propyl}-4- [ (4- { [ ( { [4 531. 6 (methyloxy) phenyl] methyl} amino) acetyl] amin o} phenyl) ethynyl] benzamide 876 H, ° °H aro 4- [ (4- { [ ( { [4- (1, 1- it. dirnethylethyl) phenyl] methyl} amino) acetyl) am NH HN ino} phenyl) ethynyl]-N-{(l S, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 877 N- { (lS, 2R)-2-hydroxy-l- O-OH [ (hYdroxyamino) carbonyl] propyl}-4-({4-[({[(4 546 5 o'r r-46. 5 nitrophenyl) methyl] amino} acetyl) amino] phen yl} ethynyl) benzamide 878 N- { (lS, 2R)-2-hydroxy-l- "°-°H ^_ [ (hydroxyamino) carbonyl] propyl}-4- { [4- 0, Nx ; ° ( { [ ( {4- 585. 5 [ (trifluoromethyl) oxy] phenyl} methyl) amino] ac 879 etyl} amino) phenyl] ethynyl} benzamide o. . N- { (lS, 2R)-2-hydroxy-l- 0 [ (hYdroxYamino) carbonyllpropyll-4- [ (4-1 [ (1 [4 mNHJLNv O (methylthio) phenyl] methyl} amino) acetyl] amin o} phenyl) ethynyl] benzamide 880 N- { (lS, 2R)-2-hydroxy-l- F+F vNXN-OH [(hydroxyamino) carbonyl] propyl}-4- { [4- k1-°H pp ° (f [ ( {4-601. 6 [(trifluoromethyl) thio] phenyl} methyl) amino] a 881 cetyl} amino) phenyl] ethynyl} benzamide N- { (lS, 2R)-2-hydroxy-1- _ . p. a-°H [ (hydroxyamino) carbonyl] propyl}-4- [ (4- { [ ( { [4 Y Y) p Y] Y}) ty] 579. 6 ° T3 NH bta-r ° (methylsulfonyl) phenyl] methyl} amino) acetyl] a. 6 mino} phenyl) ethynyl] benzamide 882 , c cH c... 4- ( {4- [ ( { [ (2, 5- F difluorophenyl) methyl] amino} acetyl) amino] ph fjLfj-t enyl} ethynyl)-N- { (lS, 2R)-2-hydroxy-l- F [(hydroxyamino) carbonyl] propyl} benzamide 883 Example Structure Name MH+ Name NM+ -4- ( {4- [ ( { [ (2, 6- F difluorophenyl) methyll amino) acetyl) arnino] ph 537 5 cm-, enyl} ethynyl)-N- { (1S, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 884 4- ( {4- [ ( { [ (3, 4- Sa4N-OH difluorophenyl) methyl] amino} acetyl) amino] ph 537. 5 enyl} ethynyl)-N-I (IS, 2R)-2-hydroxy-l- [(hydroxyamino) carbonyl] propyl} benzamide 885 4- ( {4- [ ( { [ (3, 4- H. COH atM' L\t. L' H dichlorophenyl) methyl] amino} acetyl) amino] p 570. 4 henyllethynyl)-N-f (IS, 2R)-2-hydroxy-l- [ (hydroxyamino) carbonyl] propyl} benzamide 886 4- ( {4- [ ( {I (3, 4_ 0 ; , M-O- dimethylphenyl) methyl] amino} acetyl) amino] p 529 6 H, CmNtNHe ° henyl} ethynyl)-N-{(lS, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 887 4-({4-[({[(3, 5- M, C., OH ChM"L\t. t. \J dichlorophenyl) methyl] amino} acetyl) amino] p 570 4 a@NHJiL< O henyl} ethynyl)-N-{(lS, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 888 4-[(4-{[({[3, 5- F ° °"_ °"°°l bis (trifluoromethyl) phenyl] methyl} amino) acet F F - FFAH-JQ vg a O yl] amino} phenyl) ethynyl]-N-{(lS, 2R)-2-637. 5 F hydroxy-l- 889 [(hydroxyamino) carbonyl] propyl} benzamide 88 N- { S, 2R)-2-hydroxy-1- oH, gH Chlml [(hydroxyamino) carbonyl] propyl}-4-({4- -O- K { [ (3, 4- 555. 5 F trifluorophenyl) methyl] amino} acetyl) amino] p 890 henyl} ethynyl) benzamide uoU N-{(lS, 2R)-2-hydroxy-1- "'° °"°""° [ (hydroxyamino carbonyl] propyl}-4- ( {4- [ ( { [ (2, 4, 5- 555. 5 F trifluorophenyl) methyl] amino} acetyl) amino] p 891 henyl} ethynyl) benzamide N-{(lS, 2R)-2-hydroxy-1- 2 Y NH [(hydroxyamino) carbonyl] propyl}-4-({4- zazou F \ aaa [ ( { [ (3, 4, 5- 555. 5 trifluorophenyl) methyl] amino} acetyl) amino] p 892 henyl} ethynyl) benzamide Example structure Name MH+ N- [ (1 S)-1- (aminomethyl)-2- (hydroxyamino)-2 H p-°H oxoethyl]-4- [ (4- 466. 6 , O<aSaC {[(pentylamino) acetyl] amino} phenyl) ethynyl] benzamide 893 HzN Chi l N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 ° pp-°H oxoethyl]-4- { [4- ( { [ (thien-2- 4g2. 6 ylmethvl) amino] acetyllamino) phenyl] ethynyl} benzamide 894 lion N o.. ! N- [ (lS)-l- (aminomethyl)-2- (hydroxyammo)-2- oxoethyl]-4- [ (4-1 [ (4-phenylpiperidin-l- 540. 6 yl) acetyl] amino} phenyl) ethynyl] benzamide 895 °) NH N-[(l S)-1-(aminomethyl)-2-(hydroxyamino)-2 p-OH 0 oxoethyl]-4- [ (4-f [ (4-phenylpiperazin-l- 541. 6 yl) acetyl] amino} phenyl) ethynyl] benzamide 896 N- [ (lS)-l- (aminomethyl)-2- (hydroxyammo)-2 C M) YN-O. oxoethyl]-4-1 [4- ( ( [4- (2- 559. 6 fluorophenyl) piperazin-l- 897 yl] acetyl} amino) phenyl] ethynyl} benzamide 897 N- N Chlml N-[(1 S)-1-(aminomethyl)-2-(hydroxyamino)-2 oxoethyl]-4- { [4- ( { [4- (4- fluorophenyl) piperazin-l- 559. 6 898 yl] acetyl} amino) phenyl] ethynyl} benzamide 898 NN 4-f [4- (f [ (l-acetylpiperidin-4- I ? Yl) (cyclopropyl) amino] acetyl} amino) phenyl] et hynyl}-N- [ (lS)-I- (aminomethyl)-2- 561. 7 (hydroxyamino)-2-oxoethyl] benzamide 899 o"1 "'N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 'I-OH m-, W-N-0 oxoetliyl]-4-f [4- (f [ (2, 3- 506. 6 dimethylcyclohexyl) amino] acetyl} amino) phen yl] ethynyl} benzamide 900 N- S)-1-(aminomethyl)-2-(hydroxyamino)-2 FN °""a'oxoethyl]-4- { [4- (f [ (lR, 2R, 4S)- bicyclo [2. 2. 1] hept-2- 490. 6 H ylamino] acetyl} amino) phenyl] ethynyl} benzam 901 ide Example Structure Name MH+ N- [ ( 1 S)-1- (aminomethyl)-2- (hydroxyamino)-2- 'l. Mc oxoethyl]-4- [ (4- { [ ( { [ (lS, 2R, 5S)-6, 6- p'l°r dimethylbicyclo [3. 1. 1] hept-2- 532. 7 H H yl] methyl} amino) acetyl] amino} phenyl) ethynyl 902] benzamide N-[(1 S)-l-(aminomethyl)-2-(hydroxyamino)-2 Y'"'oxoethyl]-4- { [4- ( { [ (lS, 4R)-bicyclo [2. 2. 1] hept 2-490. 6 ylamino] acetyl} amino) phenyl] ethynyl} benzam 903 ide N- N ( 1 S)-1- (aminomethyl)-2- (hydroxyamino)-2 H, N p, , s 14C c oxoethyl]-4- (14- [ (I [ (lS, 2S, 3S, 5R)-2, 6, 6- trimethylbicyclo [3. 1. 1] hept-3- 532. 7 yllamino} acetyl) amino] phenyl} ethynyl) benza 904 mide ) N N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 oxoethyl]-4-1 [4- ( { [ (tricyclo [3. 3. 1. 1-3, 7-] dec- 1-544. 7 Ha, ylinethyl) amino] acetyl} amino) phenyl] ethynyl} 905 benzamide n, N o. . N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2 oxoethyl]-4- (f4- [ (I [ (2, 6- 522. 5 a difluorophenyl) methyl] amino} acetyl) amino] ph F enyl} ethynyl) benzamide 906 N- [ ( 1 S)-1- (aminomethyl)-2- (hydroxyamino)-2 YN oxoethyl]-4- [ (4-f [ (1 [4- ck- (methylthio) phenyllmethyllamino) acetyl] amin o} phenyl) ethynyl] benzamide 907 N- [ (lS)-l- (ammomethyl)-2- (hydroxyamino)-2 "'os i, : : N'lop-°H oxoethyl]-4- [ (4- { [ ( { [4_ (methylsulfonyl) phenyl] methyl} amino) acetyl] a mino} phenyl) ethynyl] benzamide 908 N- [ (lS)-l- (an) momethyl)-2- (hydroxyammo)-2- r"a, nm 0 M-OH oxoethyl]-4-1 [4- (f [ ( {4- [ (trifluoromethyl) thio] phenyl} methyl) amino] a 586. 6 cetyl} amino) phenyl] ethynyl} benzamide 909 F F H, N Chlrol N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 H-OH oxoethyl]-4- { [4- (f [ (f4- 570. 5 [ (trifluoromethyl) oxy] phenyl} methyl) aniino] ac etyl} amino) phenyl] ethynyl} benzamide 910 ExampleStructureNameMH+ H, N a.... N- [ (lS)-l- (amiiiomethyl)-2- (hydroxyamino)-2- F oxoethyl]-4- (f4- [ (f [ (2, 4, 5- SooNSa trifluorophenyl) methyl] amino} acetyl) amino] p F henyl} ethynyl) benzamide 911 H, N mM N- [ (lS)-l- (aminomethyl)-2- (hydroxyammo)-2- p'lrp-°"oxoethyl]-4- ( {4- [ ( { [ (2, 3, 4- 9 NSaw trifluorophenyl) methyl] amino} acetyl) amino] p F henyl} ethynyl) benzamide 912 H, N Chlral N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 F P-OH oxoethyl]-4- (f4- [ (f [ (3, 4, 5- FmN Lat ° trifluorophenyl) methyl] amino} acetyl) amino] p henyl} ethynyl) benzamide 913 o" N Chlnl N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 yH-oH oxoefhyl]-4- (4- {4- [ (pyn-olidin-l- CNNHv ylacetyl) amino] phenyl} buta-1, 3- diynyl) benzamide 914 H, N Ohinl N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 0 oxoetflyl]-4- (4- {4- [ (azepan-l- 502. 6 ylacetyl) amino] phenyl} buta-1, 3- 915 diynyl) benzamide 915 H, N ChiRl N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 Xa4N-OH oxoethyl-4-(4- {4-[(piperazin-1-489 ylacetyl) amino] phenyl} buta-1, 3- diynyl) benzamide 916 H, N Chl, l N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 o_ta4NH-OH oxoethyl]-4-[4-(4-{[(4-methylpiperazin-1- NONAaY ° yl) acetyl] amino} phenyl) buta-1, 3-503. 6 diynyl] benzamide 917 H, N Chlral N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 oxoethyl]-4- (4- {4- [ (morpholin-4- 0-JL ylacetyl) amino] phenyl} buta-l, 3- diynyl) benzamide 918 ""^ N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 . Y--''" oxoethyl]-4- {4- [4- 0'"'a ' ( { [cyclohexyl (methyl) amino] acetyl} ammo) phi nyl] buta-1, 3-diynyl} benzamide 919 Example structure Name H, N Chlml N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2 ;, i ; ° p'lo'p-°"oxoethyl]-4- (4- {4- [ ( { [ (2_ WHJL m-fluorophenyl) methyl] amino} acetyl) amino] phe nyl} buta-1, 3-diynyl) benzamide 920 H, N N- [ (IS)-l- (aniinomethyl)-2- (hydroxyarnino)-2. _ r p-p-°"'oxoethyl]-4- (4- {4- [ ( { [ (3_ FJONJLar fluorophenyl) methyl] amino} acetyl) amino] phe nyl} buta-1, 3-diynyl) benzamide 921 H, N Chlel N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 F 4-OH oxoethyl]-4- (4-14- [ (I [ (4- 528. 6 fluorophenyl) methyllamino) acetyl) amino] phe nyl} buta-1, 3-diynyl) benzamide 922 x, Han N- [ S)-1-(aminomethyl)-2-(hydroxyamino)-2 0 oxoethyl]-4- (4-14- [ (I [ (2- 524. 6 methylphenyl) methyl] amino} acetyl) amino] phe nyl} buta-1, 3-diynyl) benzamide 923 N- [ ( 1 S)-l- (aminomethyl)-2- (hydroxyamino)-2 H-OH oxoethyl]-4- (4-14- [ (I [ (3- 524. 6 methylphenyl) methyl] amino} acetyl) amino] phe nyl} buta-1, 3-diynyl) benzamide 924 N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 21 oxoethyl]-4- (4-14- [ (f [ (4- meth 1 hen 1 meth 1 amino ace 1 amino he 524. 6 p Yp Y) Y]} tY)] P nyl} buta-1, 3-diynyl) benzamide 925 ", N ,, ro, N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 Hy M-OH oxoethyl]-4-14- [4- (f [ (pyridin-2- 511. 6 ° ylmethyl) amino] acetyl} amino) phenyl] buta-1, 3 diynyl} benzamide 926 NN N- [ (IS)-l- (aminomethyl)-2- (hydroxyaniino)-2. - yP.-. H oxoethyl]-4-14- [4- (I [ (pyridin-3- Nt NJLar yhmethyl) amino] acetyl} amino) phenyl] buta-l, 3 p Y Y)] tY}) p Y] diynyl} benzamide 927 eh, N- [ (lS)-l- (aminomethyI)-2- (hydroxyamino)-2- oxoethyl]-4-14- [4- ( { [ (pyridin-4- anzac ylmethyl) amino] acetyl} amino) phenyl] buta-1, 3 p Y Y)] tY}) p Y] diynyl} benzamide 928 Egam le Structure Name MH+ fN N- [ (IS)-I- (aniinomethyl)-2- (hydroxyamino)-2. b-ON a o oxoethyl]-4- [4- (4- { [ ( { [2- 540. 6 OICE (methyloxy) phenyl] methyl} amino) acetyl] amin 929 o) phenyl) buta-1, 3-diynyl] benzamide 929 H, N Chlol N- [ S)-1-(aminomethyl)-2-(hydroxyamino)-2 aa-°"oxoethyl]-4- [4- (4- { [ ( { [3_ (Y Y) p Y) Y}) ty] 540. 6 H'ba meth lox hen 1 meth 1 amino ace 1 ami. n o} phenyl) buta-1, 3-diynyl] benzamide 930 R. N MT. 1 N- [ S)-1-(aminomethyl)-2-(hydroxyamino)-2 ,. , <-H\"-""oxoethy !]-4- [4- (4- { [ ( { [4- g g (methyloxy) phenyl] methyl) amino) acetyl] amm o} phenyl) buta-l, 3-diynyl] benzamide 931 lN Chl. 1 N- [ (IS)-l- (aminomethyl)-2- (hydroxyamino)-2. , ;-r ap-'oxoethyl]-4- {4- [4- ( { [ (2- 514. 5 con fluorophenyl) amino) acetyl} amino) phenyl] buta 1, 3-diynyl} benzamide 932 ,--\, M °""N- [ (lS)-l- (aminomeihyl)-2- (hydroxyammo)-2- p, _p'lr oxoethyl)-4- {4- [4- ( { [ (3- fluorophenyl) amino] acetyl} amino) phenyl] buta F 1, 3-diynyl} benzamide 933 H, N o, M N- [ (lS)-l- (amuiomethyl)-2- (hydroxyammo)-2- b-N a,, ; _ a o oxoethyl]-4- {4- [4- ( { [(4 514 fluorophenyl) amino] acetyl} amino) phenyl] buta 1, 3-diynyl} benzamide 934 H, N mr. ! N- [ (lS)-l- (aminoniethyl)-2- (hydroxyamino)-2' H) YH-CM oxoethyl]-4- [4- (4-1 [ (pyridin-2- a ylamino) acetyl] amino} phenyl) buta-1, 3- diynyl] benzamide 935 HN N-[(1 S)-l-(aminomethyl)-2-(hydroxyamino)-2 0 oxoethyl]-4- [4- (4-1 [ (pyridin-3- ylamino) acetyl] amino} phenyl) buta-1, 3-497. 5 diynyl] benzamide 936 " « N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 r 'li'b_, oxoethyl]-4- [4- (4- { [ (pyridin-4- 497. 5 N ylamino) acetyl] amino} phenyl) buta-1, 3- N diynyl] benzamide 937 Example structure Name MH+ H, N ch.,.. N- [ (lS)-l- (aimnomethyI)-2- (hydroxyammo)-2- p'lrb-°"oxoethyl]-4- [4- (4- r-T-'- (j { [ (cyclobutylanmio) acetyl] amino} phenyl) buta' a f [ ( Y h') tY]} p Y) 1, 3-diynyl] benzamide 938 HiNl °hlrel N- [ (1S)-1- (aminomethyl)-2- (hydroxyami. no)-2 0 0N. fl-OH oxoetllyl]-4- [4- (4- 488. 6 c clopentylamino) acetyl] amino henyl) but { [ ( Y P tY) tY]} P Y) a-1, 3-diynyl] benzamide 939 N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 C'oxoethyl]-4- [4- (4- 502. 6 502. 6 ooN$< {[(cyclohexylamino) acetyl] amino} phenyl) but 1, 3-diynyl] benzamide 940 H, N a, M N- [ (lS)-l- (aminomethyl)-2- (hydroxyammo)-2- oxoethyl]-4- [4- (4- 516. 6 us C {[(cycloheptylamino) acetyl] amino} phenyl) but a-1, 3-diynyl] benzamide 941 N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 i pb-°"oxoethyl]-4- [4- (4- H, oNAHN~ ° {[(methylamino) acetyl] amino} phenyl) buta-1, 3 diynyl] benzamide 942 a N- [ (lS)-l- (aminomethyl)-2- (hydroxyanuno)-2- : - oxoetliyl]-4- [4- (4- ~hHQaao ~ ° {[(propylamino) acetyl] amino} phenyl) buta-1, 3 diynyl] benzamide 943 HH q N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 oxoethyl]-4- [4- (4- 476. 5 H, 5, NJLaY {[(butylamino) acetyl] amino} phenyl) buta-l, 3- diynyl] benzamide 944 fun N- [ S)-1-(aminomethyl)-2-(hydroxyamino)-2 oxoethyl]-4- [4- (4- 490. 6 , unCuNvahU { [(pentylamino) acetyl] amino} phenyl) buta-1, 3- diynyl] benzamide 945 N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2- oxoethyl]-4- [4- (4- 504. 6 ( [ (hexylaniino) acetyl] aniino) phenyl) buta-1, 3- diynyl] benzamide 946 Exam le Structure Name HyN Chlrel N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 , p'1ra-°"oxoethyl]-4- {4- [4- 462. 5 HC_Ns% N_< O ({[ethyl (methyl) amino] acetyl} amino) phenyl] b 947 uta-1, 3-diynyl} benzamide 947 H, N Chlal N- S)-1-(aminomethyl)-2-(hydroxyamino)-2 , a'p-°H oxoethyl]-4- {4- [4- ( { [ (1- 462. 5 methylethyl) amino] acetyl) amino) phenyl] buta- 1, 3-diynyl} benzamide 948 H, [ ( 1 S)-1- (aminomethyl)-2- (hydroxyamino)-2 NH_°HChlrel oxoethyl]-4- {4- [4- ( { [ (2_ methylpropyl) aminolacetyl} amino) phenyl] but a-1, 3-diynyl} benzamide 949 N- [ (1 S)-1- (aminomethyl)-2- (hydroxyamino)-2 -H-o. oxoethyl]-4- {4- [4- ( { [ (2- g g HO~NH> hydroxyethyl) amino] acetyl} amino) phenyl] buta 1, 3-diynyl} benzamide 950 N- [ ( 1 S)-1- (aminomethyl)-2- (hydroxyamino)-2 ,, nra-°"' oxoethyl]-4- (4- {4- [ ( { [2_ H, c O~NJEav (methyloxy) ethyl] amino} acetyl) amino] phenyl} buta-1, 3-diynyl) benzamide 951 HN N- [ (lS)-l- (anlinomethyl)-2- (hydroxyamino)-2. a4N-OH b''p-°"oxoethyl]-4- (4- {4- [ ( { [2_ ,, NCH vEht (dimethylamino) ethyl] amino} acetyl) amino] ph enyl} buta-1, 3-diynyl) benzamide 952 H, N Chlnl N-[(1 S)-l-(aminomethyl)-2-(hydroxyamino)-2 oxoethyl]-4- {4- [4- ( { [ (2_ N r-yanoethyl) aniino] acetyl) arnino) phenyl] buta- 1, 3-diynyl} benzamide 953 N- [ ( 1 S)-1- (aminomethyl)-2- (hydroxyami. no)-2 oxoethyl]-4-f4- [4- ( { [ (thien-2- 516. 6 Yhnethyl) aniino] acetyllamino) phenyl] buta-1, 3. a Y Y)] tY}) p Y] diynyl} benzamide 954 1 N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 oxoethyl]-4- (4- {4- [ (f [ (JR)-I- 524. 6 a phenylethyl] amino} acetyl) amino] phenyl} buta- 1, 3-diynyl) benzamide 955 ExampleStructureNameMH+ H, N chM N- [ (lS)-l- (anunomethyl)-2- (hydroxyamino)-2- oxoethyl]-4- (4-14- [ ( ( [ (lS)-i- nu phenylethyl] amino} acetyl) amino] phenyl} buta- 1, 3-diynyl) benzamide 956 oH, N N Chlml N- [ S)-1-(aminomethyl)-2-(hydroxyamino)-2 oxoethyl]-4-f4- [4- (f [ (2- phenylethyl) amino] acetyl} amino) phenyl] buta- 1, 3-diynyl} benzamide 957 N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2 eHNk H-cH oxoethyl]-4- (4- {4- [ (lH-imidazol-l- N/=\NgtHv ylacetyl) amino] phenyl} buta-1, 3- diynyl) benzamide 958 N-[(1 S)-1-(aminomethyl)-2-(hydroxyamino)-2 oxoethyl]-4- {4- [4- ( { [ (1R, 2R, 4S)- H r 'lr'p bicyclo [2. 2. 1] hept-2- 514. 6 ylamino] acetyl} amino) phenyl] buta-1, 3- 959 diynyl} benzamide M, N M.. N- [ (lS)-l- (ammomethyl)-2- (hydroxyamino)-2' pb-n oxoethyl]-4- {4- [4- OwNJL ( {[(cyclohexylmethyl) amino] acetyl} amino) phe 516. 6 nyybuta-1, 3-diynyl} benzamide 960 1-LCOH Chiral -c'N- { (lS, 2R)-2-hydroxy-l- r < H o [(hydroxyamino) carbonyl] propyl}-4-[(6-423. 5 N piperidin-1-ylpyridin-3-yl) ethynyl] benzamide 961 H, oH , m N- { (1S, 2R)-2-hydroxy-1- e Hs [(hydroxyamino) carbonyl] propyl}-4-{[6-(4- methylpiperazin-1-yl) pyridin-3- yl] ethynyl} benzamide 962 FIC OH Chlral x'p-oH N- { (1S, 2R)-2-hydroxy-1- _</HN o [(hydroxyamino) carbonyl] propyl}-4- [ (6- 424. 5 HN N N--piperazin-l-ylpyridin-3-yl) ethynyl] benzamide 963 H3C~_OH Chlral HH4NH-OH 4-[(6-azepan-1-ylpyridin-3-yl) ethynyl]-N- /Nr O {(lS, 2R)-2-hydroxy-1-437. 5 964 [ (hYdroxyamino) carbonyllpropyl) benzamide 964 Exam le Structure Name MH+ ° gN OH 4-{[6-(cyclobutylarniino) pyridin-3-yl] ethynyl}- N-OH w H N-{(l S, 2R)-2-hydroxy-1-409. 5 N [ (hydroxyaliiino) carbonyl] propyl} benzamide 965 liC OH Chi.] 0 4- { [6- (cyclohexylamino) pyridin-3-yllethynyll- N- { (lS, 2R)-2-hydroxy-l- 437. 5 o-b" [ (hydroxyamino) carbonyl] propyl} benzamide 966 r : gHH ChlgI 4-{[6-(butylammo) pyridm-3-yl] ethynyl}-N- \ ° NN-oH Ir-\, r { (IS, 2R)-2-hydroxy-l- 411. 5 , [(hydroxyamino) carbonyl] propyl} benzamide [ (Y Y) Y] p PY} 967 g N-OH 4-( {6- [(2-hydroxyethyl) amino] pyridin-3- HO, - yl) ethynyl)-N-f (IS, 2R)-2-hydroxy-l- 399. 4 [ (hydroxyamino) carbonyl] propyl} benzamide 968 0 4- [ (6- { [2- (dimethylamino) ethyl] amino} pyridin H C'3 f HH o 3-yl) ethynyl]-N- {(l S, 2R)-2-hydroxy-1-426. 5 "' Np, N\ ,-a Y) YnY]- { ( )-Y y-_ , NH N [(hydroxyamino) carbonyl] propyl} benzamide 969 H, C OH ChlG, I N-{(lS, 2R)-2-hydroxy-1- H [ (hydroxyamino) carbonyl] propyl}-4- ( {6- q. 45. 5 OH N [(phenyhmethyl) arnino] pyridin-3- yl} ethynyl) benzamide 970 lC OH Chl. 1 r] gHN-OH-4-[(6-{[(4-uorophenyl) methyl] amino} pyridin 3-yl) etliynyl]-N-I (IS, 2R)-2-hydroxy-l- 463. 5 [ (hydroxyamino) carbonyl] propyl} benzamide 971 o, o oH °nm N- { (1S, 2R)-2-hydroxy-1- wHJY [(hydroxyamino) carbonyl] propyl}-4-{[6-432 4 'CVN""N (pyndin-4-ylammo) pyndm-3- yl] ethynyl} benzamide 972 HC OH Chiral b-oH 4- [ (6-chloropyridin-3-yl) ethynyl]-N- { (lys, 2R)- 2-hydroxy-1-374. 8 N- [ (hydroxyamino) carbonyl] propyl} benzamide 973 ExampleStructureNameMH+ H, CH, ChM o « sso nu 1, 1-dimethylethyl (2S)-2- [ ( {4- [ (4- M, OH ethylphenyl) ethynyl] phenyl} carbonyl) amino]- 452. 5 3- (hydroxyamino)-3-oxopropylcarbamate 974"° 974 H, Csj40 (p, N- [ (1S)-1- (aminomethyl)-2- (hydroxyamnno)-2 °"oxoethyl]-4- {4- [4- ( { [ (1S)-1- (aminomethyl)-2- HN < (hydroxyamino)-2-493. 5 HN I 1t oxoethyl] arnino} carbonyl) phenyl] buta-1, 3- 975 H, N diynyl} benzamide NsoH N- {(1 S, 2R)-2-hydroxy-1- J9HE [(hydroxyarnino) carbonyl] propyl}-4-{[4-438 5 '/ T JO. O (morpholin-4- yhnethyl) phenyl] ethynyl} benzamide 976 N 4- [(4- { [(2- HHNi° aminoethyl) amino] methyl} phenyl) ethynyl]-N-411 5 NH fY {(lS, 2R)-2-hydroxy-1- H2N~ [(hydroxyamino) carbonyl] propyl} benzamide 977 Ne Chiral H XNvOH 4-({4-[((2S)-2-amino-5- HN f [amino (imino-) methyl] amino} pentanoyl) amin o] phenyl} ethynyl)-N- [ (1S)-1- (aminomethyl)-2 "N (hydroxyamino)-2-oxoethyl] benzamide 978". H-COH (2S)-6-amino-2- ( { [4- ( {4- [ ( { (1 S, 2R)-2- hydroxy-1- "° ° [ (hydroxyamino) carbonyl] propyl} amino) carbo 511. 5 ° nyl] phenyl} ethynyl) phenyl] carbonyl} amino) he 979 NH2 xanoic acid H2C^ì, oH airal (2S)-6-amino-2-( {[4-({4-[( {(1 S, 2R)-2- NH 0 H'OH hydroxy-l- is v [(hydroxyamino) carbonyl] propyl} amino) carbo 525. 6 -J<i nyl] phenyl} ethynyl) phenyl] acetyl} amino) hexa 980 noic acid --- 0 5- { [ (2S)-3- (hydroxyamino)-3-oxo-2- ( { [4- o" (phenylethynyl) phenyl] carbonyl} amino) propyl 438. 4 iiv] amino}-5-oxopentanoic acid ' 981 0 Chiral 0n NH2 N-(2-aminoethyl)-N'-[(2S)-3-(hydroxyamino)- 3-oxo-2- ( { [4- 480. 5 (phenylethynyl) phenyl] carbonyl} amino) propyl ] pentanediamide 982, ExampleStructureNameMH+ Chiral 0=' N N- [ (IS)-l- [ (2, 6-dioxopiperidin-1-yl) methyl]-2. (hydroxyamino)-2-oxoethyl]-4-420. 4 983 (phenylethynyl) benzamide 983 N, N'-bis [ (2S)-3- (hydroxyamino)-3-oxo-2-4 (phenylethynyl) phenyl] carbonyl} amino) propyl 743. 8 ] pentanediamide 984 Choral °YT'0 N- ( (lS)-2- (hydroxyamino)-2-oxo-l- { [ ( { [ (lS)- o 1 1- HX OH phenylethyl] amino} acetyl) amino] methyl} ethyl 985 (phenylethynyl) benzamide 985 C oh N- { (1S)-2-hydroxy-1- 0 [ (hydroxyamino) carbonyl]-2-methylpropyl)-4- 353. 4 (phenylethynyl) benzamide I 986 HN Chiral ii XN-OH N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 oxoethyl]-4- [ (6-piperidin-1-ylpyndin-3- 408. 5 . J"yl) ethynyl] benzamide 987 HzN Chiral pl b_°H N- [ (1S)-1- (arninomethyl)-2- (hydroxyamino)-2 H H oxoethyl]-4-[(6-morpholin-4-ylpyridin-3-410. 4 oJN N yl) ethynyl] benzamide 988 HN o N- [ (lS)-l- (ammomethyl)-2- (hydroxyamino)-2' HC-N N'yl) pyridin-3-yl] ethynyl} benzamide 9 9 989 p b-OH N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 0 oxoethyl]-4- [ (6-piperazin-1-ylpyridin-3- 409. 5 " N yl) ethynyl] benzamide 990 HN Chiral pp-OH N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 /d o oxoethyl]-4-[(6-azepan-1-ylpyridin-3-422. 5 JAN yl) ethynyl] benzamide 991 ExampleStructureNameMH+ HzN Chiral _ N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 4N 0 oxoethyl]-4-f [6- (cyclobutylaniino) pyridin-3- 394. 4 O-HN N yl] ethynyl} benzamide 992 HzN Chiral 1 b-OH N- [ (1S)-l- (aminomethyl)-2- (hydroxyamino)-2 eJ H oxoethyl]-4-{[6-(cyclohexylamino) pyndin-3-422. 5 yl] ethynyl} benzamide 993 r N OH h N-[(lS)-l-(arnmomethyl)-2-(hydroxyamino)-2 H2CHwH o oxoethyl]-4 {[6-(butylamino) pyridin3 396. 5 N yl] ethynyl} benzamide 994 HzN N chM N- [ (lS)-l- (aminomethyl)-2- (hydroxyammo)-2 NM-OH oxoethyl]-4- [ (6-f [2- tfr-S 0 t \, lL 1-.. ..- JMO. 4 H, (methyloxy) ethyl] amino} pyridin-3- 398. 4 995 yl) ethynyl] benzamide 995 Y N N- { (1 S, 2R)-2-hydroxy-1- . b. b"o °H [ (hydroxyamino) carbonyl] propyl}-4- { [4- 436. 5 (piperidin-1- N'yhnethyl) phenyl] ethynyl} benzamide 996 ° H °H Chkal 'OH 4- [ (4- f [ (2, S)-2-amino-3- (4- J3/aminophenyl) propanoyl] amino} phenyl) ethyn ]-N-I (IS, 2R)-2-hydroxy-l- 997 1 (hYdroxYamino) carbonyl] propyl} benzamide 997 Ha ° H °H ChGal . rM 4- ( (2S)-2-ammo-3- { [4- ( {4- [ ( { (lS, 2R)-2- p H ° hydroxy-1- HiN$HJU [(hydroxyamJino) carbonyl] propyl} amino) carbo 545. 6 nyllphenyl} ethynyl) phenyl] amino}-3- 998 oH oxopropyl) benzoic acid H30tH Ch ral O p b°H H lo 573. 6 r"on OH 999 H, c"oH M N- { (lS, 2R)-2-hydroxy-l- _¢NiNOH [(hydroxyamino) carbonyl] propyl}-4-( {4-[( {[1- (hydroxymethyl)-2-497. 6 methylpropyl] aniino} acetyl) aminoJphenyl} eth HO 1000 ynyl) benzamide Example Structure Name MH+ HC H OH Chiral 0 j H iHHi 4-[4-(3-aminophenyl) buta-1, 3-diynyl]-N- < { (lS, 2R)-2-hydroxy-l- 378. 4 1001 H2Nsg [(hydroxyamino) carbonyl] propyl} benzamide 1001 HC d OH , 1- [4- (3- { [ (2_ H2N °"ammoethyl) amino] methyl} phenyl) buta-l, 3-..-- NH-diynyl]-N- {(1 S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 1002 5- [ (4- { [4- ( { [ (lS)-l- (ammomethyl)-2- vH OH (hydroxyamino)-2-453 5 0 { v oxoethyl] amino} carbonyl) phenyl] ethynyl} phe nyl) amino]-5-oxopentanoic acid 1003 ° J °""N- (2-ammoethyl)-3- {4- [4- ( { [ (lS)-l- ßH (aminomethyl)-2-(hydroxyamino)-2-434 5 434. 5 oxoethyl] aniino) carbonyl) phenyl] buta-l, 3- diynyl} benzamide 1004 NH2 Chiral p j H H°H N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 oxoethyl]-4- {4- [3- (aminomethyl) phenyl] buta- 377. 4 H2N v 1, 3-diynyl} benzamide 1005 NH2 Chiral boH N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2 oxoethyl]-4- {4- [3- 416. 4 (trifluoromethyl) phenyl] buta-1, 3- diynyl} benzamide 1006 NH Chiral O H OH ° °"N- [ ( S)-1- (aminomethyl)-2- (hydroxyamino)-2- oxoethyl]-4-buta-1, 3-diynylbenzamide zu H 1007 NH2 Chiral 0) H ) ! TM' °"N- [ (lS)-l- (aminomethyl)-2- (hydroxyammo)-2. 0 CH, oxoethyl]-4- [4- (2-methylphenyl) buta-1, 3- 362. 4 diynyl] benzamide 1008 H, C H OH Chlral T p, °" 4_ (4- {4_ [ (3_ aminopropanoyl) amino] phenyl} buta-1, 3-449 5 'diynyl)-N- { (1S, 2R)-2-hydroxy-1- 449. 5 [ (hydroxyamino) carbonyl] propyl} benzamide 1009 Example structure Name MH+ tN 4-[4-(3- i ; a"Op" { [ (aminoacetyl) amino] methyl} phenyl) buta-l, 3 449 5 H2NJIs diynyl]-N-{(lS, 2R)-2-hydroxy-1- ' [ (hydroxyamino) carbonyl] propyl} benzamide 1010 H20 H oH Chiral ejJt iNHsoH 4-(4- {3-[(aminoacetyl) amino] phenyl} buta-1, 3- diynyl)-N- { (1S, 2R)-2-hydroxy-1- 435. 4 h drox H2Nt [ (hydroxyammo) carbonyl] propyl} benzamide 0 1011 H c U OH Chiral ow 4- [4- (4- { [ (2S)-2- aminopropanoyl] amino} phenyl) buta-1, 3-449 5 °, ¢S diynyl]-N-{(l S, 2R)-2-hydroxy-1- H, b [ (hydroxyamino) carbonyl] propyl} benzamide 1012 NH ; Q ; M o Chiral XNgNHsoz 4-(4- {4-[(aminoacetyl) amino] phenyl} buta-1, 3- diynyl)-N- [ (lS)-l- (aminomethyl)-2- 40. 4 FNj N (hydroxyamino)-2-oxoethyl] benzamide b 1013 NH= q4a1 0 4-4-3 { [ (aminoacetyl) amino] methyl} phenyl) buta-1, 3 434. 5 diynyll-N- [ (lS)-I- (aminomethyl)-2- (hydroxyamino)-2-oxoethyl] benzamide 1014 NH, Chkal M, OH N- [ (lS)-l- (aminomethyl)-2- (hydroxyarnino)-2. oxoethyl]-4- (4- {4- [ (3- 434. 5 O < aminopropanoyl) amino] phenyl} buta-l, 3- H N4HM diynyl) benzamide 1015 NH Chiral d gNHaoH 4-(4- {3-[(aminoacetyl) amino] phenyl} buta-1, 3- diynyl)-N- [ (lS)-I- (aminomefliyl)-2- 420. 4 H2NAo v (hydroxyamino)-2-oxoethyl] benzamide ° 1016 Hic Chiral o C-oH -rH'OH 4- [ (4- { [ (2S)-2-amino-3- (4- hydroxyphenyl) propanoyl] amino} phenyl) ethy H N 517. 6 HJ nyl]-N- { (lS, 2R)-2-hydroxy-l- Jr [(hydroxyamino) carbonyl] propyl} benzamide 1017 HO H P L H ¢f tNHsoH 4-(4- {4-[(aminoacetyl) amino] phenyl} buta-1, 3- /diynyl)-N- {(1 S, 2R)-2-hydroxy-1-435. 4 H, NAN) C [(hydroxyamino) carbonyl] propyl} benzamide 1018 Example structure Name MH+ H2N Chirru N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 SN4N-OH oxoethyl] 4 ( {4 [ (butylamino) methyl] phenyl} ethynyl) benzami de 1019 /\H2 -hiral N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 oxoethyl]-4-1 [4- (piperidin-l- 421. 5 methyl) phenyl] ethynyl} benzamide 1020 M ; N Ch) ! a ! N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2 O--0 oxoethyl]-4- [ (4- 352. 4 formylphenyl) ethynyl] benzamide 1021 H, C OH Chìral N-{(lS, 2R)-2-hydroxy-1- _o~4N4N~OH [(hydroxyamino) carbonyl] propyl}-4-({4-5 ", °-s-H [ (methylsulfonyl) amino] phenyl} ethynyl) benza 432. 5 I- mide 1022 oH2N Chiral N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 H) Y oxoethyl]-4- (f4- 417. 5 0 ", ° o-p ° [ (methylsulfonyl) amino] phenyl} ethynyl) benza mide 1023 HzN Chiral N- [ (lS)-l- (aniinomethyl)-2- (hydroxyamino)-2. X XN-OH oxoethyl]-4 ({4 [ (Phenylsulfonyl) amino] phenyl) ethynyl) benza mide 1024 H, N N N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 a9 0 oxoethyl]-4- (4-f4- 503. 5 <D s° H r [(phenylsulfonyl) amino] phenyl} buta-1, 3-, diynyl) benzamide 1025 HzN Chiral N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 oxoefliyl]-4-1 [4- (moipholin-4- 423. 5 yhnethyl) phenyl] ethynyl} benzamide 1026 0han Chlral N_ [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 'N ZD O) ym-. H oxoethyl]-4- (f4- [ (4-methylpiperazin-l- 436. 5 yl) methyl] phenyl} ethynyl) benzamide 1027 Example structure Name MH+ ch. ra N- [ (lS)-l- (ammomethyl)-2- (hydroxyammo)-2. oxoethyl]-4- [ (4- { [ (2- 3g7. 4 hydroxyethyl) amino] methyl} phenyl) ethynyl] b enzamide 1028 H2N Chlrr2 N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 H-OH oxoethyl]-4- { [4- (f [2- H3Co~NHo</° (methyloxy) ethyl] amino} methyl) phenyl] ethyn yl} benzamide 1029 N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 ; i '10" °"oxoethyl]-4- ( { _ [ (cyclohexylamino) methyl] phenyl} ethynyl) ben zamide 1030 H2N Chl.] N- [ (IS)-l- (aniinomethyl)-2- (hydroxyamino)-2. 0 M-OH oxoethyl]-4- [ (4- 443. 5 1 [ (phenyhnediyl) aniinolmedlyl} phenyl) ethyny 443. 5 Ijbenzamide 1031 °) HN N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 _ <Ht oxoethyl]-4-[(6-chloropyridin-3-359. 8 Cl N yl) ethynyl] benzamide 1032 N-{(lS, 2R)-2-hydroxy-1- [ (hydroxyaniino) carbonyl] propyl} (4- {4- 0 o [6- (methyloxy) pyridin-3- 542. 6 H, C-O yl] amino} acetyl) amino] phenyl} buta-l, 3- 1033 diynyl) benzamide H, °Y°" °", b 4- {4- [4- ( { [ (6-chloropyridin-3- O 3vHW yl) amino] acetyl} amino) phenyl] buta-1, 3- diynyl)-N-f (lS, 2R)-2-hydroxy-l- 547. 0 [(hydroxyamino) carbonyypropyl} benzamide 1034 H3C OH Chiral N- { (1S, 2R)-2-hydroxy-1- fT'°" [ (hydroxyammo) carbonyl] propyl}-4- { [4- C) \ Y (pyrrolidin-l- yhnethyl) phenyl] ethynyl} benzamide 1035 H, C OH Chiral + NsOH 4-({4-[(ethylamino) methyl] phenyl} ethynyl)-N- A {(lS, 2R)-2-hydroxy-1-396. 5 , icr [ (hydroxyamino) carbonyllpropyllbenzamide 1036 Example structure Name MH+ r HN 4- ( {4 . a. "o °H [ (dimethylamino) methyl] phen 1 eth 1-N- Y} YnY) ICH, j< {(lS, 2R)-2-hydroxy-1- H3C-Nw [(hydroxyamino) carbonyllpropyl} benzarr. iide 1037 Y HN N- {(1 S, 2R)-2-hydroxy-1- JNt OH [(hydroxyamino) carbonyl] propyl}-4- ( {4- [ (4- methylpiperazin-l- yl) methyl] phenyl) ethynyl) benzamide 1038 N- { (lS, 2R)-2-hydroxy-l- o C OH Chifa) p. a. oH [ (hydroxyamino) carbonyl] propyl}-4- { [4- ( { [3- H. (lH-irnidazol-l-476. 5 yl) NJSi 1 ro 1 amino meth 1 hen 1 eth 1 benz Y) P PY]} Y) p Y] YnY} 1039 amide NH Chiral oh O °H N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 'oxoethyl]-4- (4-thien-2-ylbuta-1, 3- 354. 4 1040 diynyl) benzamide 1040 o. N, N, N-tnethyl-2- { [4- (4- {4- [ ( { (lS, 2R)-2- NH , @Hi hydroxy1 cH6 [ (hydroxyamino) carbonyl] propyl} amino) carbo 520. 6 He~7SHbi nyl] phenyl} buta-l, 3-diynyl) phenyl] amino}-2- 1 oxoethanaminium 1041 H, C H OH Chlral HM, OH 4- [4- (2-aminophenyl) buta-1, 3-diynyl]-N- . ° { (lS, 2R)-2-hydroxy-l- 378. 4 [ (hydroxyamino) carbonyl] propyl} benzamide 1042 .. "4- [4- (3- { [ (2- o b 6 a°H aminoethyl) amino] methyl} phenyl) buta-1, 3-420 5 420. 5 diynyl]-N- [ (IS)-I- (aminomethyl)-2- (hydroxyamino)-2-oxoethyl] benzamide 1043 H3C^, OH Chiral jfjM'"°"4-buta-l, 3-diynyl-N- { (lS, 2R)-2-hydroxy-l- / [(hydroxyamino) carbonyl] propyl} benzamide i 1044" H-c""4- [4- (4- { [ (2S)-2-ammo-4- , a-aH ° A/H o methylpentanoyl] amino} phenyl) buta-1, 3- N. p r _ diynyl]-N- { (IS, 2R)-2-hydroxy-l- [ (hydroxyamino) carbonyl] propyl} benzamide 1045 Exam le Structure Name MI3+ gN-OH ch,, (2S)-N- [4- (4- {4- [ ( { (lS, 2R)-2-hydroxy-l- 0MI p [ (hydroxyamino carbonyl] propyl} amino) carbo [ (Y Y) Y] p pY}) 475. 5 nyllphenyl} buta-1, 3-diynyl) phenyl] pyrrolidine 2-carboxamide 1046 , c on c.. (2S)-N- [4- (4- {4- [ ( { (lS, 2R)-2-hydroxy-l- - ; y [ (hYdroxyamino) carbonyl] propyl} amino) carbo -489. 5 nyllphenyl) buta-1, 3-diynyl) phenyl] piperidine- 2-carboxamide 1047 c.., 4- [4- (4- { [ (2S)-2, 3- 0 HI diaminopropanoyl] amino} phenyl) buta-1, 3-464 5 Z. $HN~/diynyl]-N- {(1 S, 2R)-2-hydroxy-1- '" [(hydroxyamino) carbonyl] propyl} benzamide 1048 0 H, O OH ehlral p-° 4- [4- (4- { [ (2S)-2-amino-3- (lH-imidazol-4- H2NaHNr yl) propanoyl] amino} phenyl) buta-l, 3-diynyl]-515 5 N- { (1 S, 2R)-2-hydroxy-1- 1049 (hydroxyamino) carbonyl] propyl} benzamide 1049 M % N-11-1 (hYdrOxYanlino) carbonyl]-2- XN NOH (propylammo) propyl]-4-[(4-494 6 HNoA < {[(propylamino) acetyl] amino} phenyl) ethynyl] benzamide 1050 cY, 4- [ (4- H- ; 0-. H 1 [ (cyclobutylamino) acetyl] amino} phenyl) ethy 518 6 v nyl]-N-{2. (cyclobutylamino)-l- NoA v [(hydroxyamino) carbonyl] propyl} benzamide 1051 J Chim) o °x"'" N- { (1S, 2R)-2-amino-1- 1 (hYdroxYamino) carbonyl] propyl}-4- [ (4- { [ (cyclopropylamino) acetyl] amino} phenyl) eth 1052 H ynyl] benzamide 1052 H, q. NNHch) 1- [ (1R, 2S)-2- [ ( {4- [ (4- i. ° pb. °" { [ (cyclopropylamino) acetyl] amino} phenyl) eth ° ynyl] phenyl} carbonyl) amino]-3- 477. 5 VoNJ (nJa (hydroxyamino)-l-methyl-3-oxopropyl] triaza- 1053 1, 2-dien-2-ium M = N- { (lS, 2R)-2-ammo-l- , J@H o OH [(hydroxyamino) carbonyl] propyl}-4- ( {4- [ ( { [ (4 518. 6 m-, 2, jcr fluorophenyl) methyl] amino} acetyl) amino] phe 1054 nyl} ethynyl) benzamide 1054 Example structure Name MH+ zou c.,.., N- { (lS, 2R)-2-amino-l- j0"''°" [ (hydroxyammo) carbonyl] propyl}-4- ( {4- [ (I [ (3 518. 6 NJ7s Jr fluorophenyl) methyl] amino} acetyl) amino] phe nyl} ethynyl) benzamide 1055 o" ""N- { (lS, 2R)-2-amino-l- < N [(hydroxyamino) carbonyl] propyl) 4- [ (4- 452. 5 { [ (propylamino) acetyl] amino} phenyl) ethynyl] benzamide 1056 1056 ° NN N {(lS, 2R) 2amino1 vHN oH [(hydroxyamino) carbonyl] propyl}-4-{[4-500 {NJk v ({[(phenyhmethyl) amino] acetyl} amino) phenyl]. 6 ethynyl} benzamide 1057 o ° N=NH 1- ( (1R, 2S)-3- (hydroxyamino)-1-methyl-3-oxo- 0 2-1 [ (4-1 [4- ° ( { [ (phenylinethyl) amino] acetyl} amino) phenyl] 527. 6 ethynyl} PhenYl) carbonyllaminolpropyl) triaza- 1058 1, 2-dien-2-ium NH2 Chl. 1 N"H N- { (lS, 2R)-2-amino-l- j ! f1'V'°" [ (hydroxyammo) carbonyl] propyl}-4- [ (4-.. NHs m {[(cyclobutylamino) acetyl] amino} phenyl) ethy Gr H nyl] benzatnide 1059 H, N&NHchM 1- [ (1R, 2S)-2- [ ( {4- [ (4- e JYHN {[(cyclobutylamino) acetyl] amino} phenyl) ethy p nyl] phenyl} carbonyl) amino]-3-491. 5 jNAHNJtJ (hydroxyamino)-1-methyl-3-oxopropyl] triaza- 1060 1, 2-dien-2-ium H, c cH, cnira H X NH 4 _ [(4-ethylphenyl) ethynyl]-N- { (1 S)-1- [ (hydroxyamino) carbonyl]-2- 365. 4 methylpropyl} benzamide 1061 H, C OH Chiral 4- (4-14- [ (ethylamino) methyl] phenyl} buta-1, 3- ,/diynyl)-N- {(1 S, 2R)-2-hydroxy-1-420. 5 [ (hydroxyamino) carbonyl] propyl} benzamide 1062 Chlral o j H N40'oH N- [ (lS)-l- (aminomethyl)-2- (hYdroxyamino)-2. H2N oxoethyl]-4- [4- (3-aniinophenyl) buta-1, 3- 363. 4 diynyl] benzamide I 1063 Example Structure Name MH+ H, C_oH Chlrr2 N) ?'OH 4- (4-f 3- [ (4-aminobutanoyl) aniino] phenyllbuta H, i~ 1, 3-diynyl)-N- { S, 2R)-2-hydroxy-1-463. 5 ""p'i [ (hydroxyamino) carbonyl] propyl} benzamide 1064 H3C !/°H Chiral fTH'°"N- { (lS, 2R)-2-hydroxy-l- HO [ (hydroxyamino) carbonyllpropyll-4- [4- (3- 379. 4 hydroxyphenyl) buta-1, 3-diynyl] benzamide 1065 HC OH Chlral 0] n H2N ; @ eNHooH 4-(4- {2-[(aminoacetyl) amino] phenyl} buta-1, 3- O " ° diynyl)-N- { (lS, 2R)-2-hydroxy-l- 435. 4 [ (hydroxyamino) carbonyl] propyl} benzamide 1066 rNHx Cttral p'O p'"N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 , CH oxoethyll-4- {4- [2, 4-bis (methyloxy) pyrimidin- 410. 4 H2Co1S 5-yl] buta-1, 3-diynyl} benzamide 1067 1067 0H (2S)-6-aniino-2-f [ (4-f4- [4- (f [ (lS)-i- , + (aminomethyl)-2-(hydroxyammo)-2-520 H, N. o, xNX oxoethyl] ammo} carbonyl) phenyl] buta-l, 3- H° ° ° diynyl} phenyl) carbonyl] amino} hexanoic acid 1068 NHZ Chiral P J M Yj""o"N- [ (lS)-l- (ammomethyl)-2- (hydroxyammo)-2 oxoethyl]-4- [4- (2-aminophenyl) buta-1, 3- 363. 4 diynyl] benzamide 1069 NH, Chirel rX p, 4- [4- (4- {2- [ (2-aminoethyl) amino]-2- oh oxoethyl} phenyl) buta-1, 3-diynyl]-N-[(1S)-1-448 (aminomethyl)-2- (hydroxyamino)-2- HiN"v ( 1070 oxoethyl] benzamide 1070 NH2 Chiral /N N-[(1S)-1-(aminomethyl)-2-(hydroxyamino)-2 oxoethyl]-4- [4- (2-aminopyrimidin-5-yl) buta- 365. 4 N 1, 3-diynyl] benzamide 1 071 H2N N HAN N 1071 NH, a, M 4- (4-f 3- [ (4-arninobutanoyl) an-jino] phenyl} buta 1, 3-diynyl)-N- [ (lS)-1- (aminomethyl)-2- 448. 5 H2N f X, (hydroxyamino)-2-oxoethyl] benzamide 1072 Exarnple Structure Name MH+ NH Chiral H H, (, OH 4- (4- f2- [ (aminoacetyl) aniino] phenyllbuta-1, 3- .)-NIH diynyl)-N- [ (lS)-I- (aminomethyl)-2- 420. 4 (hydroxyamino)-2-oxoethyl] benzamide 1073 -. H 4- [4- (4- {2- [ (2-oethyl) amino]-2- 0 0 oxoethyl) phenyl) buta-1, 3-diynyl]-N-{(lS, 2R)-463 5 < < 4oo. o 2-hydroxy-l- Na [ (hydroxyamino) carbonyl] propyl} benzamide 1074 4- [4- (4- { [ (2, 3- dihydroxypropyl) amino] methyl} phenyl) buta- 466. 5 °I H rV 1, 3-diynyl]-N-{(1 S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 1075 r OH ('hlrsl N- { (1S, 2R)-2-hydroxy-1- XH/> OH [(hydroxyamino) carbonyl] propyl}-4- (4- {4- , v [({[2-51 2. 6 (methyloxy) phenyl] methyl} amino) methyl] phe 1076 nyl} buta-1, 3-diynyl) benzamide 1076 H, C oH Chlral N- { (lS, 2R)-2-hydroxy-l- [ (hydroxyamino) carbonyllpropyl}-4- (4-14- NH Jg [(pyridin-2-ylamino) methyl] phenyl} buta-1, 3-u. z 1077 fjS diynyl) benzamide 1077 ""4- [4- (4- { [ (2- aminoethyl) amino] methyl} phenyl) buta-1, 3-435 5 diynyl]-N- { (1S, 2R)-2-hydroxy-1- i HiN [ (hydroxyamino) carbonyl] propyl} benzamide 1078 S CH3iShlraì JoH 4- [ (4-ethyIphenyl) ethynyl]-N- [ (lR)-l- [ (ethylthio) methyl]-2- (hydroxyamino)-2- 397. 5 oxoethyl] benzamide 1079 r s S CH, Chlral 4- [ (4- { [ (2S)-2- aminopropanoyl] amino} phenyl) ethynyl]-N- q55. 5 "N i [ (1R)-1- [ (ethylthio) methyl]-2- (hydroxyamino) CH2 2-oxoethyl] benzamide 1080 Nix choral o) H . N'*T on N- [ (lS)-l- (ammomethyl)-2- (hydroxyamino)-2- oxoethyl]-4- [4- (3-chlorophenyl) buta-1, 3- 382. 8 diynyl] benzamide 1081 ExampleStructureNameMH+ NHz Chiral 9 i M OH N- [ (IS)-I- (aminomethyl)-2- (hydroxyamino)-2. oxoethyl]-4- {4- [3- (methyloxy) phenyl] buta-1, 3 378. 4 diynyl} benzamide 1082 H, C OH Chlral oH N- { (lS, 2R)-2-hydroxy-l- it [(hydroxyamino) carbonyl] propyl}-4- (4- {4- meth lsulfon 1 amino hen 1 buta-1 3-456. 5 H, C-Fj-H diynyl) benzamide 1083 H, C OH Chlral o"'N- { (lS, 2R)-2-hydroxy-l- H 0 [ (hydroxyamino) carbonyllpropyll-4- (4-13- 456. 5, °O N v [(methylsulfonyl) amino] phenyl} buta-1, 3-56. 5 \ H coss W diynyl) benzamide 1084 NH2 Chiral P J H .. NTT"o"N- [ (lS)-l- (ammomethyl)-2- (hydroxyamino)-2- iK oxoethyl]-4-(4-pyrazin-2-ylbuta-1, 3-350. 3 diynyl) benzamide 1085 iN H30 OH Chiral eHN) > OH N-{(lS, 2R)-2-hydroxy-1- o % [ (hydroxyamino) carbonyl] propyl}-4- [4- (3- 408. 4 nitrophenyl) buta-1, 3-diynyl] benzamide 1086 O XH N-{(lS, 2R)-2-hydroxy-1- R, C, I H 0 [ (hydroxyamino) carbonyl] propyl}-4-[(3-446 5 "S-I [ (methylsulfonyl) aminolmethyllphenyl) ethyn I yl] benamide 1087 OH, C OH Chiral O x' H ° e XN>OH 4-[(2-formylphenyl) ethynyl]-N-{(lS, 2R)-2- hydroxy-1-367. 4 [ (hydroxyamino) carbonyl] propyl} benzamide 1 088 1088 X N- { (l R, 2R)-2-hydroxy-1- o" [ (hydroxyamino) carbonyl] propyl}-4- [ (3- Ha Ó<NY {[(methylsulfonyl) amino] methyl} phenyl) ethyn yl] benzamide 1089 H, C OH Chiral OH 4- (12- [ (aniinoacetyl) aniino] phenyl) ethynyl)-N. 1 A {(lS, 2R)-2-hydroxy-1-411. 4 [ [(hydroxyamino) carbonyl] propyl} benzamide 1 090 1090 Example structure Name ME+ hic OH Chiral OH N- {(1 S)-2-hydroxy-1- o 1 (hydroxyaniino) carbonyl] propyl}-4-f 4- [3-462. 5 |N/ (morpholin-4-yltnethyl) phenyl] buta-1, 3- diynyl} benzamide 1091 HzN Chiral N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2 HHX-OH oxoethyl]-4-({4-367 4 H3C-0 1 (metl'Ylamino) metllyllphenylletliynyl) benzam ide 1092 HiN Chiral N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 i ° pb-°"oxoethyl]-4- ( {4- 381. 4 HCv Nsr/O [(ethylamino) methyl] phenyl} ethynyl) benzami de 1093 N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 HH4N-oH oxoethyl]-4-({4-395 5 H, C~N t O [(propylamino) methyl] phenyl} ethynyl) benzam ide 1094 N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 =, v ° pb-°H oxoethyl]-4- ( {4_ H, Cw Ne/O [(pentylamino) methyl] phenyl} ethynyl) benzam ide 1095 N- [ (lS)-l- (ammomethyl)-2- (hydroxyammo)-2- I,. ° pb-°H oxoethyl]-4- ( {4_ M. Ir \r- o hex lamino meth 1 hen 1 eth 1 benzami 437. 6 [ (Y) Y] P Y} YnY) de 1096 H, N, ChS ral N- [ S)-1-(aminomethyl)-2-(hydroxyamino)-2 vHX oxoethyl]-4-[(4- { [(1-395 5 methylethyl) aminolmethyllphenyl) ethynyl] ben en.-j zamide 1097 H, N Chlral N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 SH4N-oH oxoethyl]-4 [(4 { [(2 H CtN</o methylpropyl) amino] methyl} phenyl) ethynyl] b 409. 5 enzamide 1 098 1098 H, N Chirsl N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 H3C M 0 oxoethyl]-4- [ (4- f [ (1, 1-409. 5 HaCxc dirnethylethyl) amino] methyl} phenyl) ethynyl] b enzamide 1099 Example structure Name M1 I+ H2N Chiral N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 , \ oxoetllyl]-4- (14- H CNt/O [(dimethylarnino) methyl] phenyl} ethynyl) benz amide 1100 HzN Chpal N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 fN\"°"oxoethyl]-4- [ (4- HCvNt O {[ethyl (methyl) amino] methyl} phenyl) ethynyl] benzamide 1101 N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 X, XN H oxoethyl] 4-{[4 ({[2 424 5 OH, C (dimethylammo) ethyl] arnino} methyl) phenyl] et hynyl} benzamide 1102 N- [ ( 1 S)-1- (aininomethyl)-2- (hydroxyamino)-2 r oxoetliyl]-4-f [4- (f [4- 'CH, C (dimethylamino) butyl] amino} methyl) phenyl] et hynyl} benzarnide 1103 "iN p N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 N -OH oxoethyl]-4- [ (4-1 [ (2- 406. 5 cyanoethyl) amino] methyl) phenyl) ethynyl] ben zamide 1104 . . 4- { [4- ( { [2- SH4N-OH (acetylarnmo) ethyl] amino} methyl) phenyl] ethy 438. 5 nyll-N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2-oxoethyl] benzamide 1105 H, c.,., 4- [ (4- { [ (2- f-. JH-oH ammoethyl) amino] methyl} phenyl) ethpyl]-N- 396. 5 "zN-. [ (1 S)-1- (aminomethyl)-2- (hydroxyamino)-2- oxoethyl] benzamide 1106 HiN ChIrdI N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 oHX oxoethyl]-4-[(4-{[(3-41 1 5 hydroxypropyl) amino] methyl} phenyl) ethynyl] benzamide 1107 HiN Chirel N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 H-OH oxoethyl]-4-1 [4- (f [3-425. 5 ° (methyloxy) propyl] amino} methyl) phenyl] ethy nyl} benzamide 1108 ExampleStructureNameMH+ H2N Chlml N- S)-1-(aminomethyl)-2-(hydroxyamino)-2 q4s 4N-OH oxoethyl]-4- { [4-( {methyl [2-42 5 5 HC o~Nt/H o (methyloxy) ethyl] amino} methyl) phenyl] ethyn yl} benzamide 1109 N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 °,, ; ° pb-°"oxoethyl]-4- { [4- ( { [3- (2-oxopyrrolidin-1- 47g, 6 yl) propyllaminolmethyl) phenyl] ethynyl} benz amide 1110 N- [ ( 1 S)-1- (aminomethyl)-2- (hydroxyamino)-2 M-OH oxoethyl]-4- [ (4-f [ (3-morpholin-4- 480. 6 ylpropyl) amino] methyl} phenyl) ethynyl] benza mide 1111 HiN Chiral N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 m. M-OH oxoethyl]-4- ( (4- 393. 5 c [ (cyclopropylamino) methyl] phenyl} ethynyl) be [ (Y p pY) Y] P Y} YnY) nzamide 1112 HzN Chiral N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 b-°"oxoethyl]-4- ( {4- [ (cyclobutylamino) methyl] phenyl} ethynyl) ben d zamide 1113 HEIN Chiral N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 = i pp °"oxoethyl]-4- ( {4_ [ (cyclopentylamino) methyl] phenyl} ethynyl) be 421. 5 nzamide 1114 Chiral N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2 oxoetliyl]-4- (14- 449. 6 [ (cycloheptylamino) methyl] phenyl} ethynyl) be 449. 6 nzamide 1115 H,NN Chlral N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 oxoethyl]-4- ( {4- 463. 6 [ (cyclooctylamino) methyl] phenyl} ethynyl) ben zamide 1116 o 2 XN-[(1 S)-l-(aminomethyl)-2-(hydroxyamino)-2 C < o oxoethyl]-4-{[4-(pylrolidin-1-407. 5 Dimethyl) phenyl] ethynyl} benzamide 1117 ExamDle structure Name MlI+ Sl H °""'N- [ (lS)-l- (ammomethyl)-2- (hydroxyammo)-2- 0 oxoethyl]-4-1 [4- (azepan-l- 435. 5 yhnethyl) phenyl] ethynyl} benzamide 1118 N- [ (lS)-l- (aminomethyl)-2- (hydroxyami. no)-2 oxoethyl]-4- [ (4- { [ (3R)-3- 450. 6 = r b °N 450. 6 (dimethylamino) pyrrolidin-l- yl] methyl} phenyl) ethynyl] benzamide 1119 N- N C l S)-l- (aminomethyl)-2- (hydroxyamino)-2 "'°'H°"'r ° . b-°"°hl oxoethyl]-4- [ (4- { [ (3S)-3- 450. 6 tNw O (dimethylamino) pyrrolidin-l- yl] methyl} phenyl) ethynyl] benzamide 1120 HzN 4- [ (4- { [ (3R)-3- (acetylamino) pyrrolidin-1- . -N°" yl] methyl} phenyl) ethynyl]-N- [ (lS)-l-. (aminometllyl)-2- (hydroxyamino)-2- oxoethyl] benzamide 1121 ° H2N Chlml 4-[(4-{[(3S)-3-(acetylamino) pylrolidin-1- oO-OH yl] nletliyl} phenyl) ethynyl]-N- [ (l S)-1- (aniinomethyl)-2- (hydroxyamino)-2- 464. 5 oxoethyl] benzamide 1122 °" N- [ (lS)-l- (ammomethyl)-2- (hydroxyammo)-2. oxoethyl]-4-f [4- (1, 4'-bipiperidin-11- 504. 6 yhnethyl) phenyl] ethynyl} benzamide 1123 H2N Chiral N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2 J'°"oxoe&yl]-4- [ (4- O N\< O {[(cyclohexyhmethyl) amino] methyl} phenyl) eth ynyl] benzamide 1124 H2N Chln} N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 .--W-oxoethyl]-4- [ (4- g g O'"r { [cyclohexyl (methyl) amino] methyl} phenyl) eth ynyl] benzamide 1125 HsN °hlral N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 eHk oxoethyl]-4- { [4-( { [(1 R)-1-457 5 phenylethyl] amino} methYl) phenyl] ethynyl} be nzamide 1126 Example structure Name MH+ N-j (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 = N OH oxo ethyl] 4 { [4- ( { [ (1S)-1_ phenylethyl] amino) methyl) phenyl] ethynyllbe ° P Y Y]} Y) p Y] YnY} nzamide 1127 N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 -M oxoethyl]-4- [ (4-1 [ (thien-2- 449. 5 , Nxr O yhmethyl) amino] methyl} phenyl) ethynyl] benza mide 1128 N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2 ay-oH oxoethyl]-4- [ (4-1 [ (2- 457. 5 phenylethyl) amino] methyl} phenyl) ethynyl] ben zamide 1129 H2N Chlml .- ?, L, R-oH N- [ (lS)-l- (ammomethyl)-2- (hydroxyammo)-2- oxoethyl]-4- (f4- [ (piperidin-3- 436. 5 ylamino) methyl] phenyl} ethynyl) benzamide 1130 HzN XN-oH N-[(1 S)-l-(aminomethyl)-2-(hydroxyamino)-2 N tH o oxoethyl]-4-({4-[(piperidin-4-436. 5 ylamino) methyl] phenyl} ethynyl) benzamide 1131 N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 0 M-OH oxoethyl]-4- [ (4- { [ (piperidin-2- 450. 6 yhnethyl) amino] methyl} phenyl) ethynyl] benza mide 1132 H3N °hiral N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 H yJM-oH oxoethyl]-4- [ (4- { [ (pipendin-3-. aNo 5/0 ylmethyl) amino] methyl} phenyl) ethynyl] benza mide 1133 N- [ (lS)-I- (aniinomethyl)-2- (hydroxyarnino)-2. 0ny M-CH oxoethyl]-4-1 [4- ( [ (2R)-pyrrolidin-2- 436. 5 yhnethyl] aniino) mefllyl) phenyl] ethynyl} benza mide 1134 "iN Chlral N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2 0 oxoethyl]-4-f [4- (f [ (2S)-pyrrolidin-2- 436. 5 yhnethyl] amino) methyl) phenyl] ethynyl} benza mide 1135 Example Structure Name MH+ HN Chipai 0N-OH N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2. b r ° oxoethyl]-4- ( {4- [ (pyrrolidin-3- 422. 5 amino) methyl] phenyl} ethynyl) benzamide 1136 HiN °htral N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 H-OH oxoethyl]-4-1 [4- ( { [ (2_ ° fluorophenyl) methyl] amino} methyl) phenyl] euh F ynyl} benzamide 1137 child N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2 r ° . b-°H oxoethyl]-4- { [4- ( { [ (3- F fluoroPhenyl) methyllani*mo) methyl) phenyl] eth ynyl} enzamide 1138 Han N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 n"-"oxoethyl]-4- { [4- ( { [ (4- fluorophenyl) methyl] amino} methyl) phenyl] eth ynyl} benzamide 1139 O N Chiral N- [ (lS)-i- (aminomethyl)-2- (hydroxyamino)-2 = r pb °H oxoethyl]-4- { [4- ( { [ (2- 457. 5 methylphenyl) methyl] ammo} methyl) phenyl] et CH hynyl} benzamide 1140 N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 r p. a-°" oxoethyl]-4- { [4- ( { [ (3- H, °-a r : ° methylphenyl) methyl] amino} methyl) phenyl] et hynyl} benzamide 1141 N- [ ( 1 S)-l- (aminomethyl)-2- (hydroxyamino)-2 pb-°Hm oxoethyl]-4- { [4- ( { [ (4- 457. 5 methylphenyl) methyl] amino} methyl) phenyl] et hynyl} benzamide 1142 H N Chiral N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 b r = r ° pb-°H oxoethyl]-4- ( {4- [ (f [2- methyloxy) phenyl] methyl amino methyl] phe 'nyl} ethynyl) benzamide 1143 N- [ ( 1lS)-1- (aminomethyl)-2- (hydroxyaxnino)-2 0-'"oxoethyl]-4- ( {4- [ ( { [3- gg methyloxy) phenyl] methyl} amino) methyl] phe (Y Y) p Y] Y}) Y] P nyl} ethynyl) benzamide 1144 ExampleStructureNameMH+ mp H2N Chinl ( 1 S)-1- (aminomethyl)-2- (hydroxyamino)-2 --o."oxoethyl]-4- ( {4- [ ( { [4- (methyloxy) phenyl] methyl} amino) methyl] phe nyl} ethynyl) benzamide 1145 H2N N ch ! N- [ (lS)-l- (ammomethyl)-2- (hydroxyamino)-2- oym-.. oxoethyll-4- (14- C [(phenylamino) methyl] phenyl} ethynyl) benzam ide 1146 HaN N viral N- [ S)-1-(aminomethyl)-2-(hydroxyamino)-2 oxoethyl]-4- [ (4- ( [ (pyridin-3- 444. 5 yhnethyl) aniino] methyllphenyl) ethynyl] benza mide 1147 f''1 °'""N- [ (lS)-l- (ammomethyl)-2- (hydroxyammo)-2. N r., _ r ° a''b-°"oxoethyl]-4- ( {4- [ (4-phenylpiperidin-1- 497. 6 yl) methyl] phenyl} ethynyl) benzamide 1148 " "°"' 'N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2 oxoethyl]-4- (14- [ (4-phenylpiperazin-l- 498. 6 yl) methyl] phenyl} ethynyl) benzamide 1149 H3N ChimI N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 "-°"oxoethyl]-4- [ (4- { [ (lR, 2R, 4S)- 447. 5 G-C bicyclo [2. 2. 1] hept-2- ylamino] methyl} phenyl) ethynyl] benzamide 1150 N- S)-1-(aminomethyl)-2-(hydroxyamino)-2 HO CH, N, N Chlal oxoethyl]-4- ( {4- [ ( { [ (1S, 2R, 5S)-6, 6- AN HH O dimethylbicyclo [3. 1. 1] hept-2- 489. 6 yl] methyl} amino) methyl] phenyl} ethynyl) benz 1151 amide FLN Chlral p-° N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 F8_HNY/N o oxoethyl]-4-[(4- { [(1 S, 4R)-bicyclo [2. 2. 1] hept- 447. 5 IF 2-ylamino] methyl} phenyl) ethynyl] benzamide 1152 "aN Chnal N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 HC C6 oxoethyl]-4-f [4- (f [ (lS, 2S, 3S, 5R)-2, 6, 6- trimethylbicyclo [3. 1. 1] hept-3- 1 amino meth 1 hen 1 eth 1 benzamide 1153 1153 Exa le Structure Name MH mp H _ T7=N=N". I 1- ( (lR, 2S)-3- (hydroxyamino)-l-methyl-3-oxo- "-°"2- { [ (4- { [4- ( { [ (pyridin-4- ° ylnethyl) amino] acetyl} amino) phenyl] ethynyl} 528. 6 , HNglNg phenyl) carbonyl] amino} propyl) triaza-1, 2-dien 1154 2-ium H. NHChl. 1 1- ( (IR, 2S)-3- (hydroxyaniino)-l-methyl-3-oxo- 2- { [ (4- { [4- ( { [ (pyridm-3- N ~ o yhmethyl) amino] acetyl} amino) phenyl] ethynyl} 528. 6 phenyl) carbonyl] amino} propyl) triaza-1, 2-dien 1155 2-ium NH3 Chiral N- { S, 2R)-2-amino-1- N [ (hydroxyamino) carbonyl] propyl}-4- { [4- N o < ({[(pyridin-4-501. 6 _, Y, mo ylmethyl) mlino] acetyl} amino) phenyl] ethynyl} 1156 benzamide nob 0c c, N- { (lS, 2R)-2-ammo-l- NHi N OH [ (hydroxyamino) carbonyl] propyl}-4- { [4- (1 [ (pyridin-3- 501. 6 p ylmethyl) amino] acetyl} amino) phenyl] ethynyl} 1157 benzamide H ° g HH3 N- [1- [(hydroxyamino) carbonyl]-2- JO (methylamino) propyl]-4- { [4- g g (f [ (phenylmethyl) amino] acetyl} amino) phenyl] "''fj' m'i b ethynyl} benzamide 1158 Hoch 0) ; H. XNOH {[(cyclobutylamino) acetyl] amino} phenyl) ethy 478. 6 nyl]-N-[l-[(hydroxyamino) carbonyl]-2- 1-7'N (methylamino) propyl] benzamide 1159 4- [ (4- { [ (2S)-2- S OH gN aminopropanoyl] amino} phenyl) ethynyl]-N- _AS H ° [(lR)-l-{[ethyl (hydroxy)-lamBda~4N-473. 6 TNJN sulfanyllmethyl}-2- (hydroxyamino)-2- 1160 CHS oxoethyl] benzamide 0 N'OH _) H 4-[(4-ethylphenyl) ethynyl]-N- H, C hydroxybenzainide H3Cu/+ 1161 NH, chira) 0) H po"N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 F oxoethyl]-4- [4- (2, 4-difluorophenyl) buta-1, 3- 384. 4 'diynyl] benzamide F 1162 Example Structure Name MH+ NH Chiral 0 ! H OH N- [ (lS)-l- (an-iinomethyl)-2- (hydroxyaniino)-2. NHz ° ° oxoethyl]-4- [ (2- 339. 4 aminophenyl) ethynyl] benzamide 1163 4>N^oH N-[(1 S)-l-(aminomethyl)-2-(hydroxyamino)-2 0 oxoethyl]-4- [4- (3- H, _, _ ° oxoethyl]-4- [4- (3- 455. 5 op, H [ (methylsulfonyl) amino] methyl} phenyl) buta- 455. 5 1, 3-diynyl] benzamide 1164 NH, N- [ (lS)-I- (aminomethyl)-2- (hydroxyaniino)-2. H3CS} oxoethyl]-4- [4- (3- ótt, {[(methylsulfonyl) amino] methyl} phenyl) buta-455. 5 1, 3-diynyl] benzamide 1165 o Chiral N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 p ° °"oxoethyl]-4- ( {3- [ (methylsulfonyl) amino] phenyl} ethynyl) benza o mide 1166 Chiral JC' 4- [ (4- { [ (2S)-2- o S aminopropanoyl] amino} phenyl) ethynyl]-N- 324. 4 HN hydroxybenzamide 1167 cH3 H c."''- /p-N_ HN OH aminoethyl) amino'jmethyl} phenyl) ethynyl]-N-411 5 { (lS, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 1168 O aC NH2 Chiral e H if OH N- { (l R, 2R)-2-amino-1- o [ (hydroxyamino) carbonyl] propyl}-4- 338. 4 ° (phenylethynyl) benzamide I 1169 C NH Chiral OH N- { (lS, 2R)-2-amino-l- ° [ (hydroxyamino) carbonyl] propyl}-4- [4- (4- 377. 4 F6N aminophenyl) buta-1, 3-diynyl] benzamide H, N 1170 NH, cHr.. N- [ (lS)-l- (ammomethyl)-2- (hydroxyamino)-2- OH oxoethyl]-4- [4- (3-hydroxyphenyl) buta-1, 3- 364. 4 diynyl] benzamide 1171 Example Structure Name MH+ N- [ (lS)-l- (aniinomethyl)-2- (hydroxyaniino)-2. 0\-P oxoethyl]-4-f 4- [3- (morpholin-4- 447. 5 yhnethyl) phenyl] buta-1, 3-diynyl} benzamide 1172 N-{(lS, 2R)-2-hydroxy-1- , 6C OH [ (hy (froxyamino) carbonyllpropyl}-4- (f4- [ (1 [2- O (methyloxy) phenyl] methyl} amino) methyl] phe nyl} ethynyl) benzamide 1173 4- [ (4- { [ (2, 3- p, _ ° p Y a\°"°h dihydroxypropyl) amino] methyl} phenyl) ethyny 442. 5 I]-N-f (1 S, 2R)-2-hydroxy-l- [ (hydroxyamino) carbonyl] propyl} benzamide 1174 cHg ch. 4- ( {2- Ci [ (dimethylamino) methyl] phenyl} ethynyl)-N- 6 » HCHN 8 sOH {(lS, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 1175 HtC OH Chiml N-{(lS, 2R)-2-hydroxy-1- o M-OH [ (hydroxyairiino) carbonyl] propyl}-4- ( {4- 382. 4 [ (methylamino) methyl] phenyl} ethynyl) benzam ide 1176 N- { (lS, 2R)-2-hydroxy-1- - °" [ (hydroxyamino) carbonyl] propyl}-4- ( {4- 410. 5 H, ~HNX [(propylamino) methyll, phenyl} ethynyl) benzam ide 1177 H C OH chl'. 1 4- (f4- [ (butylamino) methyl] phenyl} ethynyl)-N. a o p °" { (1S, 2R)-2-hydroxy-1- 424. 5 [ (hydroxyamino) carbonyl] propyl} benzamide 1178 OH OH ( 1 S, 2R)-2-hydroxy-1- H, ° orf c, arei p b-°H [ (hydroxyamino) carbonyl] propyl}-4- ( {4- q. 38. 5 n. f-ss"S,, . 11 n i\i 4oo. o H, Cm [(pentylamino) methyl] phenyl} ethynyl) benzam ide 1179 4- ( {4- [ (hexylamino) methyl] phenyl} ethynyl)-N f (1 S, 2R)-2-hydroxy- I-452. 6 [(hydroxyamino) carbonyl] propyl} benzamide 1180 Example Structure Name AM+ H, OH Chins N- { (lS, 2R)-2-hydroxy-1- , i pb-°" [ (hydroxyamino) carbonyl] propyl}-4- [ (4-f [ (I- H, o, 4'c methylethyl) amino] methyl} phenyl) ethynyl] ben zamide 1181 N-I (IS, 2R)-2-hydroxy-l- _, pb-°" [ (hydroxyamino) carbonyl] propyl}-4-[(4-{[(2-424 5 H, C) » tJ methylpropyl) amino] methyl} phenyl) ethynyl] b enzamide 1182 ", ° °"°hm 4- [ (4- { [ (1, 1- diniethylethyl) aminolmethyllphenyl) ethynyl]- N- { (lS, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 1183 H, C OH Chhal 4-[(4- _ r b-°" { [ethyl (methyl) amino] methyl} phenyl) ethynyl] 410 5 H, CV N _W N- { (l S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 1184 H3C OH Chl. 1 4-1 [4- (1 [2- __ r p,-b-°" (dimethylamino) ethyl] amino} methyl) phenyl] et hynyl}-N-f (1 S, 2R)-2-hydroxy- 1- CF6 [ (hydroxyamino) carbonyl] propyl} benzamide 1185 ) tC OH Chl. 1 4-1 [4- (f [4- Y H-OH (dimethylamino) butyl] amino} methyl) phenyl] et 'cH, hynyl}-N- {(1 S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 1186 HZC OH Chlal 4-[(4-{[(2- hYdroxYethyl) aminolmethyllphenyl) ethynyl]- HO~HNX N- {(1 S, 2R)-2-hydroxy-1- HO [(hydroxyamino) carbonyl] propyl} benzamide 1187 N- { (1S 2R)-2-hydroxy-1- HC °H Chlal , ° pb-°" [ (hydroxyamino) carbonyl] propyl}-4- [ (4-1 [ (3- 426. 5 HO-hydroxypropyl) amino] methyl} phenyl) ethynyl] 6. benzamide 1188 N-{(lS, 2R)-2-hydroxy-1- o, ° x°'"_ °° [ (hydroxyamino) carbonyl] propyl}-4- { [4- ", °. N",, : r a o p °" ( {methyl [2- 440. 5 (methyloxy) ethyl] amino} methyl) phenyl] ethyn 1189 yl} benzamide Example Structure Name MH+ H, C oH ChlRI N- {(1 S, 2R)-2-hydroxy-1- , v ° p. b-°H [ (hydroxyamino) carbonyl] propyl}-4- { [4- ( { [2- 426. 5 , 0, 4-0-- (methyloxy) ethyl] amino} methyl) phenyl] ethyn yl} benzamide 1190 N- { (lS, 2R)-2-hydroxy-l- , pb-°H [ (hydroxyamino) carbonyl] propyl}-4- { [4- ( { [3- ^, C O N4 ; O (methyloxy) propyl] amino} methyl) phenyl] ethy Y Y) P FY]} Y) p Y] Y nyl} benzamide 1191 H, OH Chiral 4-[(4-{[(2 0 cyanoethyl) amino] methyl} phenyl) ethynyl]-N-421. 5 ° { (lS, 2R)-2-hydroxy-l- [ (hydroxyamino) carbonyl] propyl} benzamide 1192 4- { [4- ( { [2_ H-OH (acetylamino) ethyl] amino} methyl) phenyl] ethy 453. 5 nyl}-N-f (1 S, 2R)-2-hydroxy- I- [ (hydroxyamino) carbonyl] propyl} benzamide 1193 N- { ( 1 S, 2R)-2-hydroxy-1- O n'X7HN~°H [(hydroxyamino) carbonyl] propyl}-4-1 [4- (1 [3- ° pd-°N (2-oxopyrrolidin-l-493. 6 \NNy yl) propyl] amino} methyl) phenyl] ethynyl} benz 1194 amide N- { ((lS, 2R)-2-hydroxy-l- ? ° °" [ (hydroxyamino) carbonyl] propyl}-4- [ (4- { [ (3- CN N>< H morpholin4 495. 6 ylpropyl) amino] methyl} phenyl) ethynyl] benza 1195 mide Hi OH Chcn m 4- ( {4- i p-b-°H [ (cyclopropylamino) methyl] phenyl} ethynyl)-N { (1 S, 2R)-2-hydroxy-1- 408. 5 d [(hydroxyamino) carbonyl] propyl} benzamide 1196 °H, C OH Chlral 4- ( {4- i p-b-°" [ (cyclobutylamino) methyl] phenyl} ethynyl)-N- J </ {(lS, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 1197 H, OH Chiral 4~ ({4~ N [ (cyclopehtylamino) methyl] phenyl} ethynyl)-N 0 tJ {(lS, 2R)-2-hydroxy-1-6. [(hydroxyamino) carbonyl] propyl} benzamide 1198 ExampleStructureNameMH+ H, C OH Chiral 4- ( {4- b'O'b-°" [ (cyclohexylamino) methyl] phenyl} ethynyl)-N- C { S, 2R)-2-hydroxy-l- 450. 5 [(hydroxyamino) carbonyl] propyl} benzamide 1199 H oH : C OH Chiral 4-({4- p' i'I-°" [ (cycloheptylamino) methyl] phenyl} ethynyl)-N 4. 64. 6 18 {(1 S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 1200 H, OH Chl. 1 4- (f4- , r b-°" [ (cyclooctylamino) methyl] phenyl} ethynyl)-N- 0 » {(1 S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 1201 H, '"'4- { [4- (azepan-l-yImethyl) phenyl] ethynyl}-N- lf b-oH : ° { (1S, 2R)-2-hydroxy-1- 450. 5 [(hydroxyamino) carbonyl] propyl} benzamide 1202 PH3 c OH Chiral 4- [ (4-1 [ (3R)-3- (dimethylaniino) pyrrolidin-l- H, C-N r \-r pp-°H yl] methyl} phenyl) ethynyl]-N- { (1S, 2R)-2- i/r---ss-. "a j, 4bo. b N hydroxy-l- [ (hydroxyamino) carbonyl] propyl} benzamide 1203 ", ° °", 4- [ (4- { [ (3S)-3- (dimethylamino) pyrrolidin-1- pb-°H yl] methyl} phenyl) ethynyl]-N- { (1S, 2R)-2- (1 fr-s&-"&.,. 00. 0 hydroxy-1-465. hydroxy-l- 1204 (hydroxyamino) carbonyl] propyl} benzamide 1204 ° c OH Chiral 4- [ (4-f [ (3R)-3- (acetylaniino) pyrrolidin-l- H, Yllmethyl} phenyl) etliynyl]-N-I (lS, 2R)-2- N hydroxy-l- 1205 [(hydroxyamino) carbonyl] propyl} benzamide 1205 ° H, C OH Chiral 4-[(4-{[(3S)-3-(acetylamino) pyrrolidin-1- "' r°"yl] methyl} phenyl) ethynyl]-N- { (1S, 2R)-2- N hydroxy-l- 1206 [(hydroxyamino) carbonyl] propyl} benzamide 1206 4- { [4- (1, 4'-bipiperidin-1'- H, C CH Chiral 0 ylmethyl) phenyl] ethynyl}-N- { (lS, 2R)-2- Ti <r--s''o i.) i 0) M. < N hydroxy-l- [(hydroxyamino) carbonyl] propyl} benzamide 1207 Example Structure Name MH+ H, C OH Chiral 4-[(4 0, M-OH 1 [ (cyclohexylmethyl) amino] methyl} phenyl) etc ynyl]-N- ( (IS, 2R)-2-hydroxy-l- 464. 6 [ (hydroxyamino) carbonyl] propyl} benzamide 1208 N- OH (lS, 2R)-2-hydroxy-l- FiC OH Chiral NA VHNX<HN-OH [(hydioxYamino) carbonyl] propyl}-4-({4-[(4-513 6 phenylpiperazin-1- yl) methyl] phenyl} ethynyl) benzamide 1209 H, OH OH Chiral N-{(lS, 2R)-2-hydroxy-1- N >HXf ~°H [(hydioxYamino) carbonyl] propyl)-4- [ (4- ( [ (2- phenylethyl) amino] methyl} phenyl) ethynyl] ben zamide 1210 N- {(1 S, 2R)-2-hydroxy-\1- H, C CH Chtral v T p-°H [ (hydroxyamino) carbonyl] propyl}-4- { [4- 472. 6 phenylethyl] amino} methyl) phenyl] ethynyl} be 1211 nzamide N- { (lS, 2R)-2-hydroxy-l- oH, ° oH °htrai p-°H [ (hydroxyamino) carbonyl] propyl}-4- { [4- p r = b o ( { [ (1S)-1- 472. 6 CH, phenylethyl] amino} methyl) phenyl] ethynyl} be 1212 nzamide N- { S, 2R)-2-hydroxy-1- SNX N-OH [(hydroxYamino) carbonyl] propyl}-4- [ (4- f [ (thien-2- 464. 6 ylmethyl) amino] methyl} phenyl) ethynyl] benza 1213 mide Y°"'N- { (lS, 2R)-2-hydroxy-l- NH_ {<H ° [(hydroxYaZino) carbonyl] propyl}-4- {4-451. 5 Çy [(piperidrn-3- ylamino) methyl] phenyl} ethynyl) benzamide 1214 H X ; N N- { (1 S, 2R)-2-hydroxy-1- NTm-o, i [ (hydroxyamino) carbonyl] propyl}-4- ( {4- ry'-U' [ (piperidin-4- HN ylamino) methyl] phenyl} ethynyl) benzamide 1215 N- { ( 1 S, 2R)-2-hydroxy-1- C OH Chiral [ (hydroxyamino) carbonyl] propyl)-4- [ (4- N'N-OH CCN SH Y {[(PiPeridin2 465. 6 methyl) amino] methyl} phenyl) ethynyl] benza 1216 mide Example Structure Name MH+ N- { S, 2R)-2-hydroxy-1- 0 [ (hydroxyamino) carbonyl] propyl)-4- [ (4- a ° { [ (piperidin-3- 465. 6 ylmethyl) amino] methyl} phenyl) ethynyl] benza 1217 mide N- { ( 1 S, 2R)-2-hydroxy-1- 0 [ (hydroxyamino) carbonyl] propyl}-4- { [4- (f [ (2R)-pyrrohdin-2- 451. 5 H yhmethyl] amino} methyl) phenyl] ethynyl} benza 1218 mide N- { ( 1 S, 2R)-2-hydroxy-1- ° "H°g, °""' [ (hydroxyamino) carbonyl] propyl}-4- { [4- (1 [ (2S)-pyrrolidin-2- 451. 5 yhnethyl] amino} methyl) phenyl] ethynyl} benza 1219 mide H. ; N N- {(1 S, 2R)-2-hydroxy-1- ul 1 (hydroxyamino) carbonyl] propyl}-4- ( {4- [ (pyrrolidin-3- ylamino) methyl] phenyl} ethynyl) benzamide 1220 FC OH Chiral 4-1 [4- (1 [ (2- fluorophenyl) methyl] amino} methyl) phenyl] eth F ynyl}-N- {(1 S, 2R)-2-hydroxy-1- F [(hydroxyamino) carbonyl] propyl} benzamide 1221 Ha CH Chiral 4 { [4 ( { [(3 0 fluorophenyl) methyl] amino} methyl) phenyl] eth F hHv ° ynyl}-N-{(lS, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 1222 °", ° °", 4- { [4- ( { [ (4_ 0-r OH chl. 1 4 F I p r \ _ r p. b-°" fluorophenyl) methyl] amino} methyl) phenyl] eth N v ynyl}-N-{(lS, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 1223 oHXCSCH Chiral N- {(1 S, 2R)-2-hydroxy-1- N Hs HN_oH [(hydroxyamino) c arb onyl] propyl} 4 { [4 ( { [ (2 472 6 methylphenyl) methyl] amino} methyl) phenyl] et hynyl} benzamide 1224 , ,. N- { (lS, 2R)-2-hydroxy-l- -. H [ (hydroxyaniino) carbonyl] propyl}-4- { [4- ( { [ (3- H, c tJ methylphenyl) methyl] amino} methyl) phenyl] et hynyl} benzamide 1225 Example Structure Name MH+ c..... N- { (lS, 2R)-2-hydroxy-l- t3, b-°" [ (hydroxyamino) carbonyl] propyl)-4-1 [4- (f [ (4- methylphenyl) methyl] amino} methyl) phenyl] et hynyl} benzamide 1226 c. . N- { (lS, 2R)-2-hydroxy-l- H-OH [ (hydroxyamino) carbonyl] propyl}-4- [ (4- HN_W o {[(phenyhmethyl) amino] methyl} phenyl) ethyny 1] benzamide 1227 OH, OH N- { (lS, 2R)-2-hydroxy-l- N H~HN_oH [(hydroxyamino) carbonyl] propyl}-4-({4-444 5 [ (phenylamino) methyl] phenyl} ethynyl) benzam ide 1228 N- { (1S, 2R)-2-hydroxy-1- 8A@NX '"" [ (hydroxyamino) carbonyl] propyl}-4- [ (4- f [ (pyridin-3- 459. 5 ylmethyl) amino] methyl} phenyl) ethynyl] benza 1229 mide H, oH Chinl 4-[(4-{[(lR, 2R, 4S)-bicyclo [2. 2. 1] hept-2- YlaminOlmethyllphenyl) ethynyl]-N-I (lS, 2R)- 462. 6 2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 1230 Chiral ° NHH-°H (3R)-N-hydroxy-3- ( { [4- < H t (phenylethynyl) phenyl] carbonyl} amino) piperi 364. 4 dine-3-carboxamide 1231 H N 0 4- (1 [4- NH (phenylethynyl) phenyl] carbonyl} amino) piperi 349. 4 dine-4-carboxylic acid 1232 HN Chiral O j\ N- {(1 S)-2-(hydroxyamino)-2-oxo-1-[(2S)- 0 0 M-OH pyrrolidin-2-yhnethyl] ethyl)-4- 378. 4 zu (phenylethynyl) benzamide 1233 Chiral o b-oH (3R)-3- { [ (4'-ethyl-1, 1'-biphenyl-4- I yl) carbonyl] amino}-N-hydroxypiperidine-3-368. 4 0 carboxamide 1234 Example Structure Name MH+ HCt°H, c'1, 1-dimethylethyl3- (4- {4- [ ( { (1S, 2R)-2- hydroxy-1- HN>= c4HN [(hydroxyamino) carbonyl] propyl} amino) carbo 'li. b. --p o °"nyl] phenyl} buta-1, 3-diynyl) phenylcarbamate 1235 HxN c o"°"'° 4- [4- (3-amino-4-methylphenyl) buta-1, 3- H3C 21 H NX (Ns H diynyl]-N- {(1 S, 2R)-2-hydroxy-1-392. 4 [(hydroxyarnino) carbonyl] propyl} benzamide 1236 H2N NHZ cmm N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 tizzy H3C 0M, OH oxoetllyl]-4- [4- (3-amino-4-metllylphenyl) buta- 377. 4 1, 3-diynyl] benzamide 1237 4-(4- {4-[(aminoacetyl) amino]-3- NHz h, e ,.. f, ""methylphenyl} buta-l, 3-diynyl)-N- [ (lS)-l- H O (aminomethyl)-2-(hydroxyamino)-2- oxoethyl] benzamide 1238 Chtral vN@NoH N-{(lS, 2R)-2-amino-1- H 0 1 (hydroxyamino) carbonyllpropyl}-4- (2- 340. 4 phenylethenyl) benzamide 1239 O Chiral XLN N-[(2R)-2-amino-3-(hydroxyamino)-3- oxopropyl]-4'-ethyl-l, l'-biphenyl-4- 328. 4 H3Czv carboxamide 1240 O Chiraì A vLHN a-oH N- [ (2R)-2-amino-3- (hydroxyamino)-3- o oxopropyl]-4- (phenylethynyl) benzamide 324. 4 1241 1241 b, N- [ (2R)-2-amino-3- (hydroxyamino)-3- H NJ''yb-o"oxopropyl]-4- (4- 340. 8 o chlorophenyl) cyclohexanecarboxamide 1242 O Chiral --n N- [ (2S)-2-amino-3- (hydroxyammo)-3- oxopropyl]-4- (4- 340. 8 ci chlorophenyl) cyclohexanecarboxamide 1243 ExampleStructureNameMH+ n, N ch) ) N- [ (lS)-l- (ammomethyl)-2- (hydroxyamino)-2 oxoethyl]-4- [2- (4- 342. 4 methylphenyl) ethyl] benzamide 1244 HaN Chiral N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2. oxoethyl] 4- [4- (4- 371. 4 H2N aminophenyl) butyl] benzamide 1245 N-{(lS, 2R)-2-hydroxy-1- niOX N-O"Ohlnl [(hydroxyam-ino) carbonyl] propyl}-4-{[4- my a ° ( { [methyl (pyridin-2- 516. 6 ylmethyl) amino] acetyl} amino) phenyl] ethynyl} 1246 benzamide . H <.... 4- { [4- ( { [ [ (2- fluorophenyl) methyll (methyl) amino] acetyl} am 533 6 -N ino) phenyl] ethynyl}-N- {(1 S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 1247 H, <. .. 4- { [4- ( { [ [ (3- , ° pa- fluorophenyl) methyls (methyl) amino] acetyl} am ino) phenyl] ethynyl}-N-{(l S, 2R)-2-hydroxy-1- [(hydroxyamino) carbonyl] propyl} benzamide 1248 °", ° °"°h.. 4- { [4- ( { [ [ (4- H, C. OH Ch) ra) \t. LL\ 0 H-oH fluorophenyl) methyl] (methyl) amino] acetyl} am 'IOL. H-0 ino) phenyl] ethynyl}-N- { (lS, 2R)-2-hydroxy-l- [(hydroxyam-ino) carbonyl] propyl} benzamide 1249 HN N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2. oxcethyl]-4- { [4- ( { [ [ (2- gg fluorophenyl) methyl] (methyl) amino] acetyl} am F ino) phenyl] ethynyl} benzamide 1250 N- N ( 1 S)-1- (aminomethyl)-2- (hydroxyamino)-2 oxoethyl]-4- { [4- ( { [ [ (3- N fluorophenyl) methyl] (methyl) amino] acetyl} am ino) phenyl] ethynyl} benzamide 1251 N- [ ( N-[(1 S)-1-(aminomethyl)-2-(hydroxyamino)-2 H, N °nirm F ° ° I, ; ° pa-°"oxoethyl]-4- { [4- ( { [ [ (4- 518. 6 N fluorophenyl) methyl] (methyl) amino] acetyl} am mo) phenyl] ethynyl} benzamide 1252 ExampleStructureNameMH+ 1 N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 y oxoethyl]-4- (f4- [ (Imethyl [ (2- F"'p r ° 514. 6 N HN methylphenyl) methyl] amino} acetyl) amino] phe nyl} ethynyl) benzamide 1253 N- Chiral ( 1 S)-1- (aminomethyl)-2- (hydroxyamino)-2 p a-OH oxoethyl]-4- ( {4- [ ( {methyl [ (4- 514. 6 methylphenyl) methyl] amino} acetyl) amino] phe nyl} ethynyl) benzamide 1254 N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 -b-°H oxoethyl]-4- { [4- 500. 6 N (I [methyl (phenyhnethyl) amino] acetyl) aniino) phenyl] ethynyl} benzamide 1255 H, o OH Chiral N-{(lS, 2R)-2-hydroxy-1- p-b-OH [ (hydroxyamino) carbonyl] propyl}-4- { [4- ç g. O ({[methyl (propyl) amino] acetyl} amino) phenyl] ethynyl} benzamide 1256 4- { [4- H) C. OH Ch) ra)"'- M-OH (f [butyl (methyl) amino] acetyl} amino) phenyl] et 481. 6 H, O NSaV ° hynyl}-N-{(1S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 1257 N- OH (lS, 2R)-2-hydroxy-l- HtCOH Chim)"''' b-°H [ (hydroxyamino) carbonyl] propyl}-4- { [4- (I [methyl (pentyl) amino] acetyl} amino) phenyl] ethynyl} benzamide 1258 4- { [4- vX>-OH ({[hexyl (methyl) amino] acetyl} amino) phenyl] e lCN thynyl}-N-f (IS, 2R)-2-hydroxy-l- [(hydroxyamino) carbonyl] propyl} benzamide 1259 N-{(lS, 2R)-2-hydroxy-1- S NX ; N-O H [(hydroxyamino) c arb onyl] prop yl}-4- { [4 y p i ;-'° ( { [methyl (1- 467. 5 methylethyl) amino] acetyl} amino) phenyl] ethyn 1260 yl} benzamide N- { ( 1 S, 2R)-2-hydroxy-1- Y°"u'"""' [ (hydroxyammo) carbonyl] propyl}-4- { [4- 'toc, ( { [methyl (2- 481. 6 "'°Np methylpropyl) amino] acetyl} amino) phenyl] eth 1261 ynyl} benzamide Example Structure. Name MH+ N-{(lS, 2R)-2-hydroxy-1- M-OH [ (hydroxyamino) carbonyl] propyl}-4- ( {4- [ (Imetliyl [ (2- 529. 6 methylphenyl) methyl] amino} acetyl) amino] phe 1262 nyl} ethynyl) benzamide N-{(lS, 2R)-2-hydroxy-1- NO OH Chiral [ (hydroxyamino) carbonyl] propyl}-4- ( {4- S2 JL {<H [({methY1 [(4 529. 6 methylphenyl) methyl] amino} acetyl) amino] phe 1263 nyl} ethynyl) benzamide lbo n, N Chiral N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 zu oxoethyl]-4- { [4- HC~N>HW H ° ({[methyl (propyl) amino] acetyl} amino) phenyl] ethynyl} benzamide 1264 N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 o p-b-°"oxoethyl]-4- { [4- ", °NJp r ° ( { [butyl (methyl) amino] acetyl} amino) phenyl] et 466. 6 hynyl} benzamide 1265 H, N Chiral N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 0N-H-OH oxoethyl]-4- { [4- 480. 6 N (I [methyl (pentyl) amino] acetyl} amino) phenyl] 480. 6 ethynyl} benzamide 1266 H, N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2 r pb-°"oxoethyl]-4- { [4_ HsOA-2>awl a o ({[hexyl (methyl) amino] acetyl} amino) phenyl] e 494. 6 thynyl} benzamide 1267 H, N Chiral N-[(1 S)-l-(aminomethyl)-2-(hydroxyamino)-2 , C H, r x HM °H OXO ethyl]-4 { [4 ( { [methyl (l- H, CrN9HAJ methylethyl) amino] acetyl} amino) phenyl] ethyn yl} benzaniide 1268 HzN Chiral N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 -yI-H-oH oxoethyl]-4- { [4- ( { [methyl (2- °II 466. 6 methylpropyl) an3ino] acetyl} amino) phenyl] eth ynyl} benzamide 1269 HiN Chiral N-[(lS)-l-(aminomethyl)-2-(hydroxyamino)-2 __HAN-OH oxoethyl]-4- { [4-( { [methyl (pyridin-2-501 6 yhnethyl) amino] acetyl} amino) phenyl] ethynyl} benzamide 1270 ExampleStructureNameMH+ oH3C °HH riral 4 {[4~ ({[(3, 4~ OH 0 dihydroxyphenyl) methyl] amino} methyl) pheny HO+i i< l] ethynyl}-N-{(l S, 2R)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl} benzamide 1271 H3C', OH Chiral FN 0 H ")-NH HN 4-({2-[(ammoacetyl) amino] phenyl} ethynyl)-N NH vlSj H o {(lS, 2S)-2-hydroxy-1-411. 4 1272 (hydroxyamino) carbonyl] propyl} benzamide 1272 1272 oH Chiral 4 XN 4-[(4-{[(2S)-2- b ° aminopropanoyl] amino} phenyl) ethynyl]-N- 425. 5 H, N I (lS, 2S)-2-hydroxy-l- '' [ (hydroxyamino) carbonyl] propyl} benzamide 1273 cri% NH2 Chiral 0 j H . (H5"°"N- [ (lS)-l- (ammomethyl)-2- (hydroxyammo)-2. oxoethyl]-4-1 [4- 395. 5 Ha°'\N \ (diethylamino) phenyl] ethynyl} benzamide J 1274 H3C NH2 Chiral p'o p°"N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 % oxoethyl]-4- {4- [4- (ethylamino) phenyl] buta- 391. 4 1, 3-diynyl} benzamide H c^ 1275 1275 Nt Chiral o f H OH °"N- [ (lS)-l- (ammomethyl)-2- (hydroxyaniino)-2- oxoethyl]-4- [ (4- { [(2-amino-2- oxoethyl) amino] methyl} phenyl) ethynyl] benza NH. r mide 1276 H3N O NH2 Cpral fTMT °"N- [ (lS)-l- (ammomethyl)-2- (hydroxyammo)-2 v oxoethyl]-4- {[4-({[1-(hydroxymethyl)-2- methylpropyl] amino} methyl) phenyl] ethynyl} b H, N enzamide 1277 NH, cr,, m -0" N- N- [ (lS)-1- (aminomethyl)-2- (hydroxyamino)-2 oxoethyl]-4- (14- [ (pyridin-2- 430. 5 ylaniino) mefllyl] phenyl} ethynyl) benzamide 1278 N NH2 Chiral N-O NoH N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 oxoethyl]-4-14- [3- (ethylaniino) phenyl] buta- 391. 4 HzN 1, 3-diynyl} benzamide 1279 ExampleStructureNameMH+ NH2 Chiral H 4 N N- [ (1S)-1- (aminomethyl)-2- (hydroxyamino)-2 H C N iP oxoethyl]-4-{[3-367. 4 (ethylamino) phenyl] ethynyl} benzamide 1280 N4 Chiral OH N- [ (lS)-I- (aniinomedlyl)-2- (hydroxyamino)-2. oxoethyl]-4- { [4- 354. 4 (hYclroxymethyl) phenyllethynyllbenzaniide 1281 NH Chiral N- [ (lS)-l- (aminomethyl)-2- (hydroxyamino)-2 OH b JJ oxoethyl]-4-{[3-395. 5 (diethYlanlino) phenyllethynyl) benzaniide 1282 Chiral H oH N-{(lS, 2S)-2-hydroxy-1- 0 M'OH [ (hYdroxYamino) carbonyllpropyl}-4-1 [4- 438. 5 (morpholin-4- yhnethyl) phenyl] ethynyl} benzamide 1283 ÇH3 Chiral H oH 4- ({,4- o p/'poH [ (dimethylamino) methyl] phenyl} ethynyl)-N- CH3, {(lS, 2S)-2-hy*oxy-1- CH3 i. H cN [ (hydroxyamino) carbonyl] propyl} benzamide 1284 1284 CH3 Chiral H-, OH N OH 4- [ (4-aminophenyl) ethynyl]-N-f (lS, 2S)-2- hydroxy-1-354. 4 [ (hydroxyamino) carbonyl] propyl} benzamide 1285 H2N CH3 Chiral H-, OH ; m, OH 4- [4- (4-aminophenyl) buta-1, 3-diynyl]-N- > {(1 S, 2S)-2-hydroxy-1-378. 4 < [(hydroxyamino) carbonyl] propyl} benzamide I 1286 han H, C- OH Chtral jTT°"1, 1-dimethylethyl 4- (4- {4- [ ( { (1S, 2R)-2- "hydroxy-1-478. 5 i [ (hydroxyamino) carbonyl] propyl} amino) carbo 1287 b nyl] phenyl} buta-1, 3-diynyl) phenylcarbamate 1287 "' Chiral N-qo'OH N- [ (l S)-l- (aniinomethyl)-2- (hydroxyamino)-2. H oxoethyl]-4- {4- [4- (f [1- (hydroxymethyl)-2- 463. 5 °t rH methylpropyl] amino} methyl) phenyl] buta-l, 3- j (diynyl} benzamide 1288 _ Example Structure Name MH+ rNH2 Chiral 0] H jTjK °"N- [ (lS)-l- (ammomethyl)-2- (hydroxyamino)-2. oxoethyl]-4- [4- (4-hydroxyphenyl) buta-1, 3- 364. 4 i diynyl] benzamide 1289 HO CH3 Chiral HOH 0OH 4- [ (2, 4-difluorophenyl) etliynyl]-N- { (lS, 2S)-2- F _ » N hydroxy-l-375. 3 [ (hydroxyamino) carbonyl] propyl} benzamide I 1290 NH2 Chiral o r H N- [ (lS)-I- (aniinomethyl)-2- (hydroxyan-iino)-2. oxoethyl]-4- {4- [4- (morpholin-4- 447. 5 ylmethyl) pheliyl] buta-1, 3-diynyllbenzamide 1291 Nu6 Chiral N- [ (lS)-l- (aminomethyl)-2- (hydroxyan-iino)-2- oxoethyl]-4- {4- [4- (hydroxymethyl) phenyl] buta-1, 3- 378. 4 HOs i diynyl} berizamide 1292 H Chiral HjCoH o H m 0m'OH 4- (13- [ (2-aniinoethyl) aniino] phenyl} ethynyl)- N- { (lS, 2R)-2-hydroxy-1- 397. 4 tH [(hydroxyarnino) carbonyl] propyl} benzamide 1293 H2N-F NHz Chiral O r H. I H 0N, OH N- [ (lS)-l- (aniinomethyl)-2- (hydroxyaniino)-2. > oxoethyl]-4-{[4-392. 3 I (trifluoromethyl) phenyl] ethynyl} benzamide 1294 F Chlral H3-OH OH (2S, 3R)-3-hydroxy-2-({[4- 1 0 (phenylethynyl) phenyl] carbonyl} amino) butano 324. 3 ic acid 1295 Chiral H3C OH N- ( (1S, 2R)-1- { [ (2- I, H O NHa aminoethyl) amino] carbonyl}-2- 366. 4 hydroxypropyl)-4- (phenylethynyl) benzamide 1296 "'°H Chlral Ha° a 1, 1-dimethylethyl (2S)-3-(hydroxyamino)-3- 4 XN oxo-2-({[4-(4-phenylbuta-1, 3-448 5 diynyl) phenyl] carbonyl} amino) propylcarbama te 1297 i Exam le Structure Name_ H, C H OH kat c. N- { (lS, 2R)-2-hydroxy-l- < [ (hydroxyamino) carbonyl] propyl}-4- (4- {4- [ (3- 505. 6 ','morpholin-4-ylpropyl) amino] phenyl} buta-1, 3- 1298 ovjN H diynyl) benzamide Li Chiral U.... Chira) h3c OH So 3 . Srk N- [ (lS, 2R)-2-hydroxy-l- ( { [2- (methylthio) phenyl] amino} carbonyl) propyl]-4 445. 6 (phenylethynyl) benzamide 1299 1299 Chfral H3C = OH b N N 1S 2R-2-h drox-1- - { () Y Y [ (FYndin-2- amino) carbonyl] propyl}-4- 400. 4 (phenylethynyl) benzamide 1300 . NH, Chtrai 0 r ffj""'° N- ( (lS)-l- (aminomethyl)-2- { [ (l, l- /dimethylethyl) oxy] amino}-2-oxoethyl)-4-(4-404. 5 ir phenylbuta-1, 3-diynyl) benzamide 1301 H3C", gOH Chiral P L H g H O N- {(1 S, 2S)-2-hydroxy-1- [ (hydroxyamino) carbonyl] propyl}-4- (4- 363. 4 phenylbuta-1, 3-diynyl) benzamide 1302 H3CHOH Chiral HzN fh O OH (2S, 3R)-N, 3-dihydroxy-2-({[4-(4-phenylbuta-349 4 1, 3-diynyl) phenyl] methyl} amino) butanamide i 1303 pH, Q) ! ra ! Chiral oyo NH 1, 1-dimethylethyl (2S)-3- (hydroxyamino)-3- i. pwH oxo-2- ( { [4- (4-phenylbuta-1, 3- 434. 5 1304 diyiayl) phenyl] methyl} amino) propylcarbamate 1304 1304 NH Ch) rat f h OH f (2S)-3-amino-N-hydroxy-2- ( { [4- (4-phenylbuta 334. 4 1305 1, 3-diynyl) phenyl] methyl} amino) propanamide 1305 OHO Chiral N N'N- [ (IS)-2- (hydroxyamino)-l- (hydroxymethyl). O 2-oxoethyl]-4-309. 2 O F+F [(trifluoromethyl) oxy] benzamide 1306 F ExampleStructureNameMH+ i N- {2-hydroxy-1- [ (hydroxyamino) carbonyl]-2- N, phenylethyl}-4-385. 3 OH [ (fluoromethyl) oxy] benzamide 1307 F O 1307'"