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 taken 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, C3-C8carbocyclyl, C6-C12 spirobicycloalkyl, adamantyl, bicyclo[2.2.1]heptanyl, bicyclo[2.2.2]octyl or a 4-8 membered heterocyclic ring, and wherein each A moiety may be further substituted with one, two, or three R3 moieties;
• W is a C5-C6heteroaryl or phenyl, and wherein each W is optionally substituted by one, two, or three R5;
• each X1 and X2 and X3 are individually and independently hydrogen, C1-C6 alkyl, or fluoro-C1-C6 alkyl wherein the alkyl chain is partially or completely fluorinated;
• Z is CX3 or N;
• Z2 is CX1 or N;
• Z3 is CH or N;
• 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, deutero-C1-C6 alkyl wherein the alkyl chain is partially or completely deuterated, branched C3-C8 alkyl, halogen, cyano, fluoro-C1-C6 alkyl wherein the alkyl chain is partially or completely fluorinated, —(CH2)m—C(O)NR8(R9), —(CH2)m—C(O)—R6, (CH2)m—C(O)R7, (CH2)m—CN, —(CH2)m—OR8, —(CH2)m—NR8(R9), or —(CH2)m—R7, wherein each alkyl or alkylene is optionally substituted with one or two C1-C6 alkyl;
• Each R6 is individually and independently hydrogen, C1-C6 alkyl, branched C3-C8 alkyl, C3-C8 cycloalkyl, —(CH2)m—CN, —(CH2)m—OR8, —(CH2)m—NR8(R9), or —(CH2)m—R7, wherein each alkyl or alkylene is optionally substituted with one or two C1-C6 alkyl;
• each R7 is independently and individually selected from the group consisting of
• and wherein the symbol (##) is the point of attachment to respective R5 or R6 moieties containing a R7 moiety;
• each R7 is optionally substituted with —(R10)p;
• each R8 and R9 is individually and independently H, C1-C6 alkyl, fluoro-C1-C6 alkyl wherein the alkyl chain is partially or completely fluorinated, or branched C3-C8 alkyl;
• each R10 is individually and independently C1-C6 alkyl, —(CH2)m—CN, (CH2)m—OR3, —(CH2)m—NR8(R9), or —(CH2)m—C(O)—R6, 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;
• each n is individually and independently 0, 1, 2, or 3;
• each p is 0, 1, 2, or 3;
• each q is 0, 1, 2, or 3;
• and with the proviso that only one of Z1 and Z2 is N.