PRC1 inhibitors and methods of treatment therewith

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 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.