Immunomodulating trifluoromethyl-aminal azalides

A Formula (1) compound

• wherein W is H or a Formula (A) compound
• wherein X is —Ra, —RcNR5R6, —RcOR7, —RcSR7, —RcN3, —RcCN or —RcX′;
• X′ is F, CI, I or Br;
• Ra, Rb, R1 and R2 are each independently H or C1-C6alkyl;
• or R1 is benzyl optionally substituted with at least one R9 substituent;
• or R1 is a —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;
• R5 and R6 are each independently selected from H;
• C1-C6alkyl or C1-C6alkoxy each optionally substituted with at least one hydroxy;
• 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, —S(O)pR8, —RcS(O)pR8, —RcNRaRb, —RcORa, —S(O)pR8NRaRb, —RcS(O)pNRaRb or —RcNRaS(O)pR8;
• or C0-C4alkylaryl, C0-C4alkylC3-C6cycloalkyl, C0-C4alkylheterocycle and C0-C4alkylheteroaryl;
• wherein the heterocycle and heteroaryl rings are a 5-6 membered monocyclic ring or a 9-10 membered fused ring, each containing at least one heteroatom selected from the group consisting of N, O and S;
• and wherein the aryl, cycloalkyl, heterocycle and heteroaryl rings are each 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, a 4-8 membered heterocyclic ring or a 5 membered heteroaryl ring, each optionally containing at least one additional heteroatom selected from N, O and S;
• 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, phenyl, a 5-6 membered heterocyclic ring or heteroaryl ring each containing at least one heteroatom selected from N, O and S;
• and wherein the cycloalkyl, phenyl, heterocycle and heteroaryl moieties are each 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-C4alkyIC3-C6cycloalkyl, halogen, oxo, hydroxy, cyano, —NRaRb, C1-C6haloalkyl, C1-C6aloalkoxy, —S(O)pR8, phenyl, and a 5-6 membered heterocyclic or heteroaryl ring each containing at least one heteroatom selected from the group consisting of 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, a 5-6 membered heterocyclic ring, a 5-6 membered heteroaryl ring, a 9-10 membered fused heteroaryl ring and wherein each heterocyclic and heteroaryl ring contain at least one heteroatom selected from the group consisting of N, O and S;
• and phenyl;
• and wherein the phenyl, heterocyclic and heteroaryl rings 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;
• and
• p is the integer 0, 1 or 2;
• stereoisomers thereof, and pharmaceutically acceptable salts thereof.