Cyclopropyl dicarboxamides and analogues that present anti-cancer and anti-proliferative activities

摘要

A compound of Formula I, or a pharmaceutically acceptable salt, enantiomer, stereoisomer, or tautomer thereof, wherein X is halogen; Z1 and Z2 are CR2; Z3 is CH; each R1 is independently and individually halogen, H, C1-C6 alkyl, branched C3-C7 alkyl, C3-C7 cycloalkyl, or -CN; each R2 is individually and independently H, halogen, C1-C6 alkyl, or cyano; R3 is -C (O) R4, -C (O) -C6-C10-aryl, -C (O) -C4-C6 heterocyclyl, or -C (O) -C5-C6 heteroaryl, where aryl is phenyl, naphthyl, tetrahydronaphthyl, indenyl, or indanyl; and with the proviso that when R3 is -C (O) -C4-C6 heterocyclyl, the heterocyclyl does not have an N to -C (O) binding point; R4 is C3-C8 cycloalkyl, C1-C7 alkyl, - (CH2) p-CN, - (CH2) p-OR6, - (CH2) p-NR6 (R7), - (CH2) p-SO2-C1- alkyl C6, - (CH2) p-aryl C6-C10, - (CH2) p-heteroaryl C5-C6, or - (CH2) p-heterocyclyl C4-C6, in which each alkyl or alkylene is optionally substituted with one or two C1-C6 alkyl; and aryl is phenyl, naphthyl, tetrahydronaphthyl, indenyl, or indanyl; each R6 and R7 is individually and independently H, C1-C6 alkyl, or branched C3-C8 alkyl; each cycloalkyl, aryl, heteroaryl, and heterocyclyl is independently substituted with - - (R25) m; each R25 is individually and independently C1-C6 alkyl, branched C3-C8 alkyl, halogen, - (CH2) m-CN, - (CH2) m-OR6, - (CH2) m-NR6 (R7), - (CH2) m-SO2-C1-C6-alkyl, - (CH2) mC (O) NR6 (R7), - (CH2) mC (O-heterocyclyl C4-C6, or - (CH2) m-heterocyclyl C4-C6, where each alkyl or alkylene is optionally substituted with one or two C1-C6 alkyl; each m is individually and independently 0, 1, 2 or 3; and p is 1, 2 or 3.