US 12,390,440 B2
Immunomodulating trifluoromethyl-aminal azalides
Todd M. Maddux, Kalamazoo, MI (US); and Tomasz Respondek, Kalamazoo, MI (US)
Assigned to Zoetis Services LLC, Parsippany, NJ (US)
Appl. No. 17/801,328
Filed by Zoetis Services LLC, Parsippany, NJ (US)
PCT Filed Mar. 11, 2021, PCT No. PCT/US2021/021889
§ 371(c)(1), (2) Date Aug. 22, 2022,
PCT Pub. No. WO2021/183754, PCT Pub. Date Sep. 16, 2021.
Claims priority of provisional application 62/988,492, filed on Mar. 12, 2020.
Prior Publication US 2023/0137567 A1, May 4, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/351 (2006.01); A61K 31/7048 (2006.01); A61K 31/7052 (2006.01); A61P 11/00 (2006.01); A61P 29/00 (2006.01); A61P 31/04 (2006.01); A61P 37/02 (2006.01); C07D 498/04 (2006.01); C07D 519/00 (2006.01); C07H 17/08 (2006.01)
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
 
1. A Formula (1) compound

OG Complex Work Unit Chemistry
wherein W is H or a Formula (A) compound

OG Complex Work Unit Chemistry
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.