N-acyl-N′-(pyridin-2-yl) ureas 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 selected from the group consisting of C1-C6 alkyl, deutero-C1-C6 alkyl wherein the alkyl chain is partially or completely deuterated, branched C3-C8alkyl, fluoroC1-C6alkyl wherein the alkyl is fully or partially fluorinated, and C3-C8carbocyclyl, and wherein each A moiety may be further substituted with one, two, or three R3 moieties;
• W is —NHC(O)R5, —NHC(O)R6, —NHC(O)N(R7)R8 or —C(O)N(R7)R8;
• X1 and X2 are individually and independently hydrogen, C1-C6 alkyl, fluoro-C1-C6 alkyl wherein the alkyl chain is partially or completely fluorinated;
• each R1 and R2 is individually and independently H, C1-C6 alkyl, fluoroC1-C6alkyl wherein the alkyl is fully or partially fluorinated, hydroxyl, C1-C6 alkoxy, fluoroC1-C6alkoxy wherein the alkyl group is fully or partially fluorinated, or cyano;
• each R3 is individually and independently H, halogen, C1-C6 alkyl, fluoro-C1-C6 alkyl wherein the alkyl chain is partially or completely fluorinated, branched C3-C8 alkyl, C3-C8 cycloalkyl, C1-C6 alkoxy, fluoro-C1-C6 alkoxy wherein the alkyl chain is partially or completely fluorinated, branched C3-C6 alkoxy, hydroxyl, or cyano;
• each R4 is individually and independently hydrogen, C1-C6 alkyl, or branched C3-C8 alkyl;
• each R5 is individually and independently hydrogen, C1-C6 alkyl, branched C3-C8 alkyl, C3-C8 cycloalkyl, —(CH2)m—CN, —(CH2)m—OR7, —(CH2)m—NR7(R8), or —(CH2)m—R6, wherein each alkylene of R5 may be further substituted with one or more C1-C6alkyl;
• each R6 is independently and individually selected from the group consisting of
• and wherein the symbol (##) is the point of attachment to respective R5 or W moieties containing a R6 moiety;
• each R6 is optionally substituted with —(R9)p;
• each R7 and R8 is individually and independently H, C1-C6 alkyl, fluoro-C1-C6 alkyl wherein the alkyl chain is partially or completely fluorinated, branched C3-C8 alkyl, —(CH2)m—CN, —(CH2)m—OR7, —(CH2)m—NR7(R8), or —(CH2)m—R6,
• each R9 is individually and independently C1-C6 alkyl, —(CH2)m—CN, —(CH2)m—OR3, —(CH2)m—NR7(R8), or —(CH2)m—C(O)—R5, wherein each alkyl or alkylene is optionally substituted with one or two C1-C6 alkyl;
• each R10 is H, 4-(C1-C4alkyl)-piperazin-1-yl, morpholinyl, piperidinyl, pyrrolidinyl or azetidinyl;
• each m is individually and independently 0, 1, 2, or 3;
• each n is individually and independently 0, 1, 2, or 3;
• each p is 0, 1, 2, or 3;
• and
• each q is 0, 1, 2, or 3.