Title:
NOVEL THIADIAZOLYL DERIVATIVES OF DNA POLYMERASE THETA INHIBITORS
Document Type and Number:
WIPO Patent Application WO/2023/060573
Kind Code:
A1
Abstract:
Poly theta inhibitor (I), X is -N-or -C-; ring A is phenyl or a five to ten membered heteroaryl ring containing, inclusive of X, one to four heteroatoms independently selected from nitrogen, oxygen, or sulfur, Ar1 is phenyl, heteroaryl, heterocyclyl, bicyclic heterocyclyl, bridged heterocyclyl, or spiroheterocyclyl, wherein each of the aforementioned ring is substituted with Ra, Rb, and/or Rc,wherein Ra and Rb are independently selected from hydrogen, alkyl, halo, haloalkyl, alkoxy, haloalkoxy, cycloalkyloxy, acyl, acylamino, monoalkylamino, dialkylamino, alkylsulfonyl,cyano, and hydroxy; or Ra and Rb, when on adjacent ring vertices, combine to form a C3-6 cycloalkyl, or Ra and Rb, when on the same ring vertex, combine to form oxo, and Rc is selected from hydrogen, alkyl, halo, haloalkyl, alkoxy, haloalkoxy, hydroxy, hydroxyalkyl, alkoxyalkyl, aminoalkyl, heterocyclylalkyl, heterocyclyloxy, aminocarbonyl; Ar2 is phenyl, heteroaryl, or cycloalkyl, wherein said phenyl and heteroaryl are substituted with Rd, Re and/or Rf, wherein Rd and Re are independently selected from hydrogen, alkyl, halo, haloalkyl, alkoxy, haloalkoxy, hydroxy, and cyano and Rf is selected from hydrogen, alkyl, cycloalkyl, halo, haloalkyl, alkoxy, haloalkoxy, hydroxy, cyano, cyanomethyl, aminocarbonylmethyl, heteroaryl, and heterocyclyl, wherein said heteroaryl and heterocyclyl of Rf are unsubstituted or substituted with one, two, or three substituents independently selected from alkyl, halo, haloalkyl, and hydroxy; R1 is hydrogen, alkyl, halo, haloalkyl, haloalkoxy, alkoxy, hydroxy, cyano, cyanoalkyl,carboxy, alkoxycarbonyl, acylamino, aminocarbonyl optionally substituted heteroaryl, hydroxyalkyl, cycloalkyl, hydroxyalkynyl, alkoxyalkyl, aminoalkyl, aminocarbonylalkyl,sulfonylalkyl, aminosulfonylalkyl, optionally substituted heteroaralkyl, or optionally substituted heterocyclylalkyl; and R2 is hydrogen, alkyl, halo, haloalkyl, haloalkoxy, or cyano; Y is O or S or NH or NRg, Rg is a C1 to C3 aliphatic group; R3 and R4 are H, C1-6 aliphatic group.
Inventors:
LI HELEN (CN)
Application Number:
PCT/CN2021/124155
Publication Date:
April 20, 2023
Filing Date:
October 15, 2021
Export Citation:
Assignee:
BEIJING DANATLAS PHARMACEUTICAL CO LTD (CN)
International Classes:
C07D285/02; A61K31/433; A61P35/00; C07D285/04; C07D417/12
Domestic Patent References:
| WO2008104524A1 | 2008-09-04 | |||
| WO2013074059A2 | 2013-05-23 | |||
| WO2010086551A1 | 2010-08-05 |
Other References:
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AN, YUE; WEI, WEI; MU, PING PING; JIA, JINYING; LÜ, JIANZHOUB; CHEN, XIN: "Synthesis and Biological Activities of N-(5-Substituted-1,3,4-thiadiazole-2-yl)-1,4-disubtituted-3-phenyl-1H-pyrazole Acylamides", YOUJI HUAXUE, vol. 30, no. 11, 31 December 2010 (2010-12-31), CN , pages 1726 - 1731, XP009545291, ISSN: 0253-2786
PATRICK MOUGENOT; CLAUDIE NAMANE; EYKMAR FETT; FLORENCE CAMY; ROMMEL DADJI-FAHUN; GWLADYS LANGOT; CATHERINE MONSEAU; BNDICTE ONOFR: "Thiadiazoles as new inhibitors of diacylglycerol acyltransferase type 1", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 22, no. 7, 2 February 2012 (2012-02-02), Amsterdam NL , pages 2497 - 2502, XP028471752, ISSN: 0960-894X, DOI: 10.1016/j.bmcl.2012.02.006
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AN, YUE; WEI, WEI; MU, PING PING; JIA, JINYING; LÜ, JIANZHOUB; CHEN, XIN: "Synthesis and Biological Activities of N-(5-Substituted-1,3,4-thiadiazole-2-yl)-1,4-disubtituted-3-phenyl-1H-pyrazole Acylamides", YOUJI HUAXUE, vol. 30, no. 11, 31 December 2010 (2010-12-31), CN , pages 1726 - 1731, XP009545291, ISSN: 0253-2786
PATRICK MOUGENOT; CLAUDIE NAMANE; EYKMAR FETT; FLORENCE CAMY; ROMMEL DADJI-FAHUN; GWLADYS LANGOT; CATHERINE MONSEAU; BNDICTE ONOFR: "Thiadiazoles as new inhibitors of diacylglycerol acyltransferase type 1", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 22, no. 7, 2 February 2012 (2012-02-02), Amsterdam NL , pages 2497 - 2502, XP028471752, ISSN: 0960-894X, DOI: 10.1016/j.bmcl.2012.02.006
WANG XICUN, LI ZHENG, DA YUXIA: "A new route to 2-(5-aryl-2-furoylamido)-5 -aryloxymethyl-1, 3, 4-thiadiazoles", SYNTHETIC COMMUNICATIONS, vol. 32, no. 7, 1 January 2002 (2002-01-01), US , pages 1105 - 1111, XP093057210, ISSN: 0039-7911, DOI: 10.1081/SCC-120003160
Attorney, Agent or Firm:
BEIJING LEPATENT INTELLECTUAL PROPERTY AGENCY (GENERAL PARTNERSHIP) (CN)
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