| CPC A61K 31/351 (2013.01) [A61K 31/7048 (2013.01); A61K 31/7052 (2013.01); A61P 11/00 (2018.01); A61P 29/00 (2018.01); A61P 31/04 (2018.01); A61P 37/02 (2018.01); C07D 498/04 (2013.01); C07D 519/00 (2013.01); C07H 17/08 (2013.01)] | 20 Claims |
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1. A Formula (1) compound,
 wherein W is H or Formula (A)
 wherein X is —Ra, —RcNR5R6, —RcOR7, —RcSR7, —RcN3, —RcCN or —RcX′;
X′ is F, Cl, I or Br;
Ring C is phenyl, naphthyl, a 5-6 membered monocyclic heteroaryl ring or a 9-11 membered fused heteroaryl ring; wherein the heteroaryl rings each contain at least one heteroatom selected from the group consisting of N, O and S; and wherein Ring C is optionally substituted with at least one R10 substituent;
Ra, Rb, R0 and R1 are each independently H or C1-C6alkyl;
or R1 is benzyl optionally substituted with at least one R9 substituent;
or R1 is —CH2Het wherein Het is a 5-6 membered heteroaryl ring containing at least one heteroatom selected from N, O and S; and wherein the heteroaryl ring is optionally substituted with at least one R9 substituent;
Rc is C1-C4alkyl;
R2 is H, C1-C6alkyl, C0-C3alkylC3-C6cycloalkyl or —C(O)NR3R4;
or R2 is C1-C3alkylaryl, a saturated or partially saturated 5- to 6-membered C1-C3alkylheterocycle ring or a 5- to 6-membered C1-C3alkylheteroaryl ring; and wherein the heterocycle ring and the heteroaryl ring each contain at least one heteroatom selected from N, O and S; and
wherein each of the cycloalkyl, aryl, heterocyclic and heteroaryl rings are optionally substituted with at least one R9 substituent;
R3 and R4 are each independently H, C1-C6alkyl, C0-C3alkylC3-C6cycloalkyl, —RcNRaRb, C0-C3alkylaryl, a saturated or partially saturated 5- to 6-membered C0-C3alkylheterocycle ring, a 5- to 6-membered monocyclic C0-C3alkylheteroaryl ring or a 9- to 11-membered fused heteroaryl ring; and wherein the heterocycle ring and the heteroaryl rings each contain at least one heteroatom selected from N, O and S; and wherein each of the cycloalkyl, aryl, heterocyclic and heteroaryl rings are optionally substituted with at least one R9 substituent;
or R3 and R4 taken together with the nitrogen atom to which they are attached form Ring A that is a 4- to 8-membered heterocyclic ring or a 5-membered heteroaryl ring, each optionally containing at least one additional heteroatom selected from N, O and S; and
wherein each ring is optionally substituted with at least one R10 substituent; and wherein each ring is optionally fused with Y;
R5 and R6 are each independently H;
or R5 and R6 are each independently C1-C6alkyl or C1-C6alkoxy each optionally substituted with at least one hydroxy;
or R5 and R6 are each independently cyano, C1-C6haloalkyl, C1-C6haloalkoxy, —C(O)R8, —C(O)NRaR8, —C(O)RcNRaRb, —C(O)ORcR8, —C(O)ONRaRb, —RcNRaC(O)R8, —RcC(O)OH, —RcC(O)NRaRb, —RcNRaC(O)H, —RcS(O)pR8, —RcNRaRb, —RcORa, —S(O)pR8, —S(O)pR8NRaRb, —RcS(O)pNRaRb or —RcNRaS(O)pR8;
or R5 and R6 are each independently C0-C4alkylaryl, C0-C4alkylC3-C6cycloalkyl, a C0-C4alkylheterocycle or C0-C4alkylheteroaryl; wherein the heterocycle and heteroaryl rings are each a 5- to 6-membered monocyclic ring or a 9- to 10-membered fused ring, and wherein each heterocyclic and heteroaryl ring contains at least one heteroatom selected from N, O and S; and wherein each of the aryl, cycloalkyl, heterocycle and heteroaryl rings are optionally substituted with at least one R10 substituent;
or R5 and R6 taken together with the nitrogen atom to which they are attached form Ring B that is a 4- to 8-membered heterocyclic ring or a 5-membered heteroaryl ring, each optionally containing at least one additional heteroatom selected from N, O and S; and
wherein each ring is optionally substituted with at least one R9 substituent; and wherein each ring is optionally fused with Y;
R7 is H, C1-C6alkyl, —RcNRaRb, —RcORa, —RcS(O)pRa, —RcNRaC(O)Rb, —RcC(O)NRaRb, —RcNRaC(O)NRaRb or —RcNRaC(O)ORb;
R8 is C1-C6alkyl, C1-C6haloalkyl, C0-C4alkylC3-C6cycloalkyl, —NRaRb or phenyl;
or R8 is a 5- to 6-membered heterocyclic ring or heteroaryl ring each containing at least one heteroatom selected from N, O and S; and wherein each of the cycloalkyl, phenyl, heterocycle and heteroaryl rings are optionally substituted with at least one substituent selected from C1-C4alkyl, halogen, C1-C4alkoxy, C1-C4haloalkyl and C1-C4haloalkoxy;
R9 is independently selected from the group consisting of C1-C6alkyl, C1-C6alkoxy, C0-C4alkylC3-C6cycloalkyl, halogen, oxo, hydroxy, cyano, —NRaRb, C1-C6haloalkyl, C1-C6haloalkoxy, —S(O)pR8, phenyl or a 5- to 6-membered heterocyclic or heteroaryl ring each containing at least one heteroatom selected from N, O and S;
R10 is independently selected from the group consisting of C1-C3alkyl, C1-C3alkoxy, C1-C3haloalkyl, C1-C3haloalkoxy, C0-C4alkylC3-C6cycloalkyl, halogen, —NRaRb, —S(O)pR8, nitro, oxo, cyano, —C(O)H, —C(O)R8, —C(O)ORa, —OC(O)ORa, —NHRcC(O)Ra, —C(O)NRaRb, hydroxy, phenyl, a 5- to 6-membered heterocyclic ring, a 5- to 6-membered heteroaryl ring or a 9- to 10-membered fused heteroaryl ring; and wherein each heterocyclic and heteroaryl ring contains at least one heteroatom selected from N, O and S; and wherein the heterocyclic ring, the heteroaryl ring and phenyl are each optionally substituted with at least one R9 substituent;
Y is phenyl, pyridinyl, pyrimidyl, pyrazolyl, thienyl, thiazolyl, triazolyl, isothiazolyl, pyrrolyl, oxazolyl, oxadiazolyl, imidazolyl, furanyl, indolyl, benzothienyl or naphthyl;
n is the integer 0, 1, 2, or 3; and
p is the integer 0, 1, or 2; stereoisomers thereof, and pharmaceutically acceptable salts thereof.
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