US 12,466,813 B2
PRC1 inhibitors and methods of treatment therewith
Tomasz Cierpicki, Ann Arbor, MI (US); Jolanta Grembecka, Ann Arbor, MI (US); Weijiang Ying, Ann Arbor, MI (US); Yiwu Yao, Ann Arbor, MI (US); Felicia Gray, Ann Arbor, MI (US); and Qingjie Zhao, Ann Arbor, MI (US)
Assigned to The Regents of the University of Michigan, Ann Arbor, MI (US)
Filed by The Regents of the University of Michigan, Ann Arbor, MI (US)
Filed on Apr. 28, 2022, as Appl. No. 17/732,124.
Application 17/732,124 is a continuation of application No. 16/434,508, filed on Jun. 7, 2019, granted, now 11,319,302.
Claims priority of provisional application 62/681,989, filed on Jun. 7, 2018.
Prior Publication US 2023/0118233 A1, Apr. 20, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 403/14 (2006.01); A61K 9/00 (2006.01); A61K 45/06 (2006.01); C07D 403/04 (2006.01); C07D 405/14 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01); C07D 471/04 (2006.01); C07D 471/16 (2006.01); C07D 493/10 (2006.01); C07D 498/06 (2006.01); C07D 498/16 (2006.01); C07D 513/16 (2006.01)
CPC C07D 403/14 (2013.01) [C07D 403/04 (2013.01); C07D 405/14 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01); C07D 471/04 (2013.01); C07D 471/16 (2013.01); C07D 493/10 (2013.01); C07D 498/06 (2013.01); C07D 498/16 (2013.01); C07D 513/16 (2013.01); A61K 9/0019 (2013.01); A61K 9/0053 (2013.01); A61K 45/06 (2013.01)] 7 Claims
OG exemplary drawing
 
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):

OG Complex Work Unit Chemistry
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 R2 is a straight, branched, or cyclic alkyl group of 1-6 carbons and comprising 0-3 halogen atoms or OH;
wherein R4 is a (CH2)0-5COOH, (CH2)0-6OH, tetrazole, —(CH2)0-5C(O)NH2, —(CH2)0-5C(O)NH(CH2)0-3, C(O)O(CH2)1-4CH3, —(CH2)0-5SO2NH2, —(CH2)0-5SO2CH3, or —NHSO2NH2 wherein X is, NH, NR5, O, or S;
wherein R5, when present, is CH3, (CH2)1-5CH3, (CH2)1-6—COOH, (CH2)1-6—CONH2, (CH2)1-6—SO2NH2, (CH2)1-6—OH, or NH2; and
wherein RA1-5, RA′1-5, RE1-5, and RE′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 C1-C6 alkyl, C1-C6 haloalkyl, —OCF3, —OH, —O(CH2)1-4CH3, CH2OH, (CH2)0-3OH, (CH2)1-5O(CH2)1-5CH3, —OR6, OCH3, O(CH2)1-3CH3, (CH2)0-2CONH2, O(CH2)1-4COOH, —(CH2)0-5NHCOR6, —(CH2)0-5CONHR6, —NH2, (CH2)0-2NH2, —(CH2)0-6SR6, —(CH2)0-4COOH, —(CH2)0-3SO2NH2, —(CH2)0-3SO2CH3, —NHSO2NH2, —NHSO2CH3, —SH, —CN, —NO2, halogen, a 5- or 6-member heteroaryl ring, a 5-6 member cycloalkyl heteroalkyl ring, —CH2-cyclobuthyl, and —(CH2)0-3—S(CH2)0-2CH3;
wherein R6, when present, is C1-C6 alkyl, C1-C5 haloalkyl, —(CH2)1-6OH, —(CH2)1-6COOH, —(CH2)1-5O(CH2)1-5CH3, —(CH2)1-6CONH2, a 5- or 6-member heteroaryl ring, or a 5-6 member cycloalkyl or heteroalkyl ring.