Cyclopropyl dicarboxamides and analogs exhibiting anti-cancer and anti-proliferative activities

A compound of Formula I,

• or a pharmaceutically acceptable salt, enantiomer, stereoisomer, or tautomer thereof,
• wherein
• X is halogen;
• Z1 and Z2 are independently CR2 or N;
• Z3 is CH or N;
• and wherein one or two of Z1, Z2 and Z3 is N;
• 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, wherein
• 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 a N bonding hand to —C(O);
• R4 is C3-C8 cycloalkyl, C1-C7 alkyl, —(CH2)p—CN, —(CH2)p—OR6, —(CH2)p—NR6(R7), —(CH2)p—SO2—C1-C6-alkyl, —(CH2)p—C6-C10-aryl, —(CH2)p—C5-C6-heteroaryl, or —(CH2)p—C4-C6-heterocyclyl, wherein
• 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 C3-C8 branched 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)m—C(O)NR6(R7), —(CH2)m—C(O)—C4-C6-heterocyclyl, or —(CH2)m—C4-C6-heterocyclyl, wherein 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.