Granted Patent B2

US 12,466,813 · App. 17/732,124 · Granted Nov 11, 2025

Inventors: Tomasz Cierpicki (Ann Arbor, MI); Jolanta Grembecka (Ann Arbor, MI); Weijiang Ying (Ann Arbor, MI); Yiwu Yao (Ann Arbor, MI); Felicia Gray (Ann Arbor, MI); Qingjie Zhao (Ann Arbor, MI)

Assignee: The Regents of the University of Michigan

C07D403/14C07D403/04C07D405/14C07D413/14C07D417/14C07D471/04C07D471/16C07D493/10C07D498/06C07D498/16C07D513/16A61K9/0019A61K9/0053A61K45/06

Abstract

Claims (13)

1 . A method of inhibiting Polycomb Repressive Complex 1 (PRC1) in a subject suffering from cancer comprising administering to the subject a PRC1 inhibitor of Formula (II):

wherein A is a 5 or 6-member aryl or heteroaryl ring, A′ is absent or is a 5 or 6-member aryl or heteroaryl ring, E is a 5 or 6-member aryl or heteroaryl ring, and E′ is absent or is a 5 or 6-member aryl or heteroaryl ring;

wherein R 2 is a straight, branched, or cyclic alkyl group of 1-6 carbons and comprising 0-3 halogen atoms or OH;

wherein R 4 is a (CH 2 ) 0-5 COOH, (CH 2 ) 0-6 OH, tetrazole, —(CH 2 ) 0-5 C(O)NH 2 , —(CH 2 ) 0-5 C(O)NH(CH 2 ) 0-3 , C(O)O(CH 2 ) 1-4 CH 3 , —(CH 2 ) 0-5 SO 2 NH 2 , —(CH 2 ) 0-5 SO 2 CH 3 , or —NHSO 2 NH 2 wherein X is, NH, NR 5 , O, or S;

wherein R 5 , when present, is CH 3 , (CH 2 ) 1-5 CH 3 , (CH 2 ) 1-6 —COOH, (CH 2 ) 1-6 —CONH 2 , (CH 2 ) 1-6 —SO 2 NH 2 , (CH 2 ) 1-6 —OH, or NH 2 ; and

wherein R A1-5 , R A′1-5 , R E1-5 , and R E′1-5 may be absent or present, may be located at any position on A, A′, E, E′, respectively, and when present is selected from C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —OCF 3 , —OH, —O(CH 2 ) 1-4 CH 3 , CH 2 OH, (CH 2 ) 0-3 OH, (CH 2 ) 1-5 O(CH 2 ) 1-5 CH 3 , —OR 6 , OCH 3 , O(CH 2 ) 1-3 CH 3 , (CH 2 ) 0-2 CONH 2 , O(CH 2 ) 1-4 COOH, —(CH 2 ) 0-5 NHCOR 6 , —(CH 2 ) 0-5 CONHR 6 , —NH 2 , (CH 2 ) 0-2 NH 2 , —(CH 2 ) 0-6 SR 6 , —(CH 2 ) 0-4 COOH, —(CH 2 ) 0-3 SO 2 NH 2 , —(CH 2 ) 0-3 SO 2 CH 3 , —NHSO 2 NH 2 , —NHSO 2 CH 3 , —SH, —CN, —NO 2 , halogen, a 5- or 6-member heteroaryl ring, a 5-6 member cycloalkyl heteroalkyl ring, —CH 2 -cyclobuthyl, and —(CH 2 ) 0-3 —S(CH 2 ) 0-2 CH 3 ;

wherein R 6 , when present, is C 1 -C 6 alkyl, C 1 -C 5 haloalkyl, —(CH 2 ) 1-6 OH, —(CH 2 ) 1-6 COOH, —(CH 2 ) 1-5 O(CH 2 ) 1-5 CH 3 , —(CH 2 ) 1-6 CONH 2 , a 5- or 6-member heteroaryl ring, or a 5-6 member cycloalkyl or heteroalkyl ring.

2 . The method of claim 1 , wherein the PRC1 inhibitor is selected from:

3 . The method of claim 1 , wherein the subject is a human.

4 . The method of claim 1 , wherein the cancer comprises leukemia, hematologic malignancy, solid tumor cancer, breast cancer, prostate cancer, colon cancer, pancreatic cancer, ovarian cancer, liver cancer or thyroid cancer.

5 . The method of claim 1 , wherein the PRC1 inhibitor is formulated as a pharmaceutical composition with a pharmaceutically acceptable carrier.

6 . The method of claim 5 , wherein the pharmaceutical composition is formulated for oral administration to a subject.

7 . The method of claim 5 , wherein the pharmaceutical composition is formulated for administration by injection.

Assignments (2)

Continuity (3)

References Cited (119)