公开(公告)号：US20250026748A1

公开(公告)日：2025-01-23

申请号：US18696850

申请日：2022-09-29

Applicant: Repare Therapeutics Inc.

Inventor： Bingcan LIU ,  Alexander PERRYMAN ,  Philippe MOCHIRIAN ,  Michel GALLANT ,  David BENDAHAN ,  Simon SURPRENANT ,  Janek SZYCHOWSKI ,  Evelyne DIETRICH ,  Boubacar SOW ,  Monica BUBENIK

IPC: C07D417/14 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/497 ,  A61K31/4985 ,  A61K31/501 ,  A61K31/506 ,  A61K31/517 ,  A61K31/5355 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/55 ,  A61K31/551 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07D491/107

Abstract: Disclosed are compounds of formula (I), wherein V is N or CR; W is optionally substituted alkylene, alkenylene, alkynylene, cycloalkylene, or arylene; X is optionally substituted heterocyclylene, heteroarylene, arylene, wherein X may be substituted with -L1-Rx, wherein L1 is —O—, —NRX1—, optionally substituted heterocyclylene, heteroarylene, or cycloalkylene, Rx is optionally substituted alkyl, heteroalkyl, heterocyclyl, heteroaryl, cycloalkyl C1-6 alkyl, or heteroaryl C1-6alkyl, and RX1 is hydrogen or optionally substituted alkyl; Y is optionally substituted heterocyclyl, heteroaryl, or aryl; Z is a H, optionally substituted alkyl, alkynyl, alkoxy, cycloalkyl, heterocyclyl, heteroaryl, or aryl; and R is hydrogen, halogen, optionally substituted alkyl, CN, cycloalkyl, alkoxy, cycloalkoxy, N(R1)2, or C(O)NHz, wherein each R1 is hydrogen alkyl, or cycloalkyl. The compounds of formula (I) are useful for inhibiting human Polymerase Theta (Polθ) and for treating cancers, such as carcinoma, sarcoma, adenocarcinoma, leukemia, lymphoma, and melanoma.