Pyridone amides 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:
• A is
• wherein the “*” is connected to the R1-substituted phenyl ring and the “#” is connected to the amide carbonyl;
• W is —(CH2)m-pyrazole optionally substituted with —(R25)m;
• X1 is halogen or C1-C6 alkyl;
• X2 is halogen or C1-C6 alkyl;
• each R1 is individually and independently halogen, H, C1-C6 alkyl, C3-C8 branched alkyl, C3-C8 cycloalkyl, C1-C6 alkoxy, branched C3-C6 alkoxy, or cyano;
• Z1 and Z2 are independently and individually CR2 or N;
• Z3 is CR3 or N;
• with the proviso that ring B is a monocyclic ring which is not a tetrazine;
• each R2 is individually and independently H, halogen, C1-C6 alkyl, C3-C8 branched alkyl, C3-C8 cycloalkyl, C1-C6 alkoxy, branched C3-C6 alkoxy, or cyano;
• R3 is —NHR4, H, —NR6(R7), C1-C8 alkyl, C2-C3 alkynyl, C3-C8 cycloalkyl, C1-C6-alkoxy-C1-C6-alkyl-, hydroxy-C1-C6-alkyl-, cyano, cyano-C1-C6-alkyl-, C1-C6-SO2—C1-C6-alkyl-, (R7)R6N—C1-C6-alkyl-, C4-C6-heterocyclyl, C4-C6-heterocyclyl-C1-C6-alkyl-, C6-C10 aryl, C5-C6-heteroaryl, or C5-C6-heteroaryl-C1-C6-alkyl-, wherein
• aryl is phenyl, naphthyl, tetrahydronaphthyl, indenyl or indanyl;
• and
• each alkyl or alkylene is optionally substituted with one or two C1-C6 alkyl;
• R4 is H, C1-C8 alkyl, C3-C8 cycloalkyl, —(CH2)m—C(O)R5, —(CH2)p—OR6, —(CH2)p—NR6(R7), —(CH2)p—CN, —(CH2)p—SO2—C1-C6-alkyl, C6-C10 aryl, —(CH2)m—C5-C6-heteroaryl, —(CH2)m—C4-C6-heterocyclyl, —(CH2)m—C(O)N(R6)-C4-C6-heterocyclyl, or —(CH2)m—C(O)N(R6)-C5-C6-heteroaryl, wherein each alkyl or alkylene is optionally substituted with one or two C1-C6 alkyl;
• R5 is C1-C7 alkyl, branched C3-C8 alkyl, C3-C8 cycloalkyl, —(CH2)m—OR6, —(CH2)m—NR6(R7), C6-C10 aryl, —(CH2)m—C5-C6-heteroaryl, or —(CH2)m—C4-C6-heterocyclyl, wherein
• aryl is phenyl, naphthyl, tetrahydronaphthyl, indenyl or indanyl;
• and
• each alkyl or alkylene is optionally substituted with one or two C1-C6 alkyl;
• each R6 and R7 is individually and independently H, C1-C6 alkyl, or branched C3-C8 alkyl;
• each R8 is individually and independently C1-C6 alkoxy, H, halogen, C1-C6 alkyl, C3-C8 branched alkyl, C3-C8 cycloalkyl, branched C3-C6 alkoxy, or cyano;
• each alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is independently and optionally 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;
• n is 0, 1, or 2;
• and
• each p is individually and independently 1, 2, or 3.