US 12,378,233 B2
Immunomodulating azalides
Mark R. Cox, Kalamazoo, MI (US); Richard Andrew Ewin, Kalamazoo, MI (US); Tomasz Respondek, Kalamazoo, MI (US); Imelda Hot, Sherman Oaks, CA (US); and Todd M. Maddux, Kalamazoo, MI (US)
Assigned to Zoetis Services LLC, Parsippany, NJ (US)
Filed by Zoetis Services LLC, Parsippany, NJ (US)
Filed on Sep. 6, 2022, as Appl. No. 17/929,777.
Claims priority of provisional application 63/241,126, filed on Sep. 7, 2021.
Prior Publication US 2023/0129040 A1, Apr. 27, 2023
Int. Cl. C07D 413/12 (2006.01); A61K 31/7052 (2006.01); A61P 11/00 (2006.01); A61P 29/00 (2006.01); A61P 37/02 (2006.01); C07D 413/14 (2006.01)
CPC C07D 413/12 (2013.01) [C07D 413/14 (2013.01)] 11 Claims
 
1. A Formula (1) compound;

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

OG Complex Work Unit Chemistry
wherein X is —(CH2)mNR5R6;
R is H, phenyl, naphthyl, a 5- or 6-member monocyclic heteroaryl ring or a 9- or 11-membered fused heteroaryl ring, wherein each of the heteroaryl rings contains at least one heteroatom selected from N, O and S; wherein each of the heteroaryl rings contains at least one heteroatom selected from N, O and S; and wherein the phenyl, naphthyl and heteroaryl rings are each substituted with (R9)n;
Ra, R0 and R1 are each independently H or C1-C6alkyl;
or R1 is benzyl optionally substituted with (R9)n;
or R1 is —CH2Het, wherein Het is a 5- or 6-membered heteroaryl ring containing at least one heteroatom selected from N, O and S; and wherein the heteroaryl ring is optionally substituted with (R9)n;
or R1 is C3-C6cycloalkyl optionally substituted with (R9)n;
Rb is H, C1-C4alkyl, C1-C4haloalkyl, C0-C3alkylphenyl, C0-C3alkylC3-C6cycloalkyl, C0-C3alkylheterocycle or C0-C3alkylheteroaryl; wherein the heterocycle is a 5- or 6-membered saturated or partially saturated monocyclic ring; the heteroaryl is a 5- or 6-membered monocyclic ring; wherein the heterocycle and heteroaryl rings each contain at least one heteroatom selected from N, O and S; and wherein the cycloalkyl, phenyl, heterocycle and heteroaryl rings are each substituted with (R9)n;
Rc is C1-C4alkyl;
R2 is H, C1-C6alkyl, —RcORb, C1-C6haloalkyl, C0-C3alkylC5-C6cycloalkyl, —RcNRaRb, —NRaRcS(O)pR8, —NRaRcC(O)NRaRc, RcCN, —RcS(O)pR8, —NRaRb, —NRbRb, C0-C3alkylaryl, C0-C3alkylheterocycle that is a 5- or 6-membered saturated or partially saturated heterocycle ring or C0-C3alkylheteroaryl, wherein the heteroaryl is a 5- or 6-membered heteroaryl ring; wherein the heterocycle and heteroaryl rings each contain at least one heteroatom selected from N, O and S; wherein the cycloalkyl, aryl, heterocyclic and heteroaryl rings are each substituted with (R9)n and wherein each ring is optionally fused with Y;
R5 and R6 taken together with the nitrogen atom to which they are attached form Ring B, wherein Ring B 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 (R9)n; and wherein each ring is optionally fused with Y;
R8 is C1-C6alkyl, C1-C6haloalkyl, C0-C4alkylC5-C6cycloalkyl, —NRaRb, phenyl, a 5- or 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 rings are each substituted with (R9)n independently selected from the group consisting of methyl, ethyl, isopropyl, methoxy, F, Cl, Br, I, oxo, cyano, —NH2, —N(CH3)2, —CF3, —CHF2 and —OCHF2;
R9 is independently selected from the group consisting of C1-C6alkyl optionally substituted with hydroxy; C1-C6alkoxy, C0-C4alkylC5-C6cycloalkyl, halo, oxo, nitro, hydroxy, —RcORb, cyano, —NRaRb, C1-C6haloalkyl, C1-C6haloalkoxy, —S(O)pR8, —SF5, phenyl; a 5- or 6-membered heterocyclic or heteroaryl ring each containing at least one heteroatom selected from the group consisting of N, O and S; and wherein the phenyl, heterocyclic and heteroaryl rings are further optionally substituted with F, Cl, cyano or —CF3;
Y is cyclopentyl, cyclohexyl, phenyl, pyridinyl, pyrimidyl, pyrazolyl, thiophenyl, thiazolyl, triazolyl, isothiazolyl, pyrrolyl, oxazolyl, oxadiazolyl, imidazolyl, furanyl or tetrahydrothiophenyl, each substituted with methyl, F, Cl, cyano, oxo or —CF3;
m is the integer 1, 2, or 3;
n is the integer 0, 1, 2 or 3; and
p is the integer 0, 1, or 2;
or a stereoisomer, or a pharmaceutically acceptable salt thereof.