Mandelamide heterocyclic compounds

摘要

Disclosed are compounds of Formula (I) or stereoisomers, salts, or prodrugs thereof, wherein: Q is, or R1 is phenyl substituted with zero to 3 substituents; and R1, R2, R3, R4, R5, and G are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.;

主权项

1. A compound of Formula (I): or a pharmaceutically acceptable salt thereof, wherein: Q is R1 is:
(i) C3-6alkyl;(ii) C3-7cycloalkyl substituted with zero to 3 substituents independently selected from halo, —CN, C1-4alkyl, C1-4alkoxy, C1-3fluoroalkyl, C1-3chloroalkyl, and/or C1-2fluoroalkoxy;(iii) phenyl substituted with zero to 3 substituents independently selected from halo, —CN, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-3fluoroalkyl, C1-3chloroalkyl, and/or C1-2fluoroalkoxy; or(iv) pyridinyl substituted with zero to 3 substituents independently selected from halo, —CN, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-3fluoroalkyl, C1-3chloroalkyl, and/or C1-2fluoroalkoxy; R2 is C1-6alkyl, C1-3fluoroalkyl, C3-7cycloalkyl, or phenyl substituted with zero to 3 substituents independently selected from halo, —CN, C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, C1-3fluoroalkyl, C1-3chloroalkyl, and/or C1-2fluoroalkoxy; n is zero, 1, or 2; each R3 is independently C1-3alkyl, F, Cl, C1-3fluoroalkyl, C1-3chloroalkyl, —CN, C1-3alkoxy, and/or C1-3fluoroalkoxy; R4 is H or —CH3; R5 is H or —CH3; and G is:
(i) H, C1-6alkyl, or C3-6cycloalkyl;(ii) C1-6alkyl substituted with —NH2, C1-6alkoxy, —C(O)OH, —C(O)O(C1-6alkyl), or —S(O)2C1-6alkyl;(iii) C1-6alkyl substituted with one or more substituents selected from —OH, —CN, and/or cyclopropyl;(iv) —(CH2)0-3—Ra, wherein Ra is C3-6cycloalkyl substituted with zero to 2 substituents independently selected from —OH, —CN, and/or —CH2OH;(v) —(CH2)0-3—Rb, wherein Rb is phenyl substituted with zero to 2 substituents independently selected from —OH, C1-3hydroxyalkyl, and/or —S(O)2NH2;(vi) —(CH2)1-3C(O)NRcRd, wherein Rc is H or —CH3; and Rd is H, C1-6-alkyl, C3-6cycloalkyl, C1-6hydroxyalkyl, —(CH2)0-2(heteroaryl), or —(CH2)0-2(heterocyclyl);(vii) —CH(CN)Re, wherein Re is phenyl, benzyl, —C(O)NH2, or —C(O)NH(C1-3alkyl);(viii) —CHRfC(O)NH(CH3), wherein Rf is C1-6alkyl, —CN, phenyl, benzyl, or —CH2CH2-phenyl;(ix) —(CH2)1-3NHC(O)Rg, wherein Rg is C1-6alkyl or —O(C1-6alkyl);(x) —CHRh—(CH2)0-3—Ri, wherein Rh is H or —CH3, and Ri is heteroaryl;(xi) —(CH2)0-3—Rj, wherein Rj is heterocyclyl; or(xii) —(CH2)1-3C(O)—Rk, wherein Rk is  and each Rx is independently selected from H, F, —OH, —CH3, —OCH3, and/or —C(O)OCH3; wherein each of said heteroaryl groups is substituted with zero to three substituents independently selected from C1-3alkyl, —OH, —NH2, phenyl, methylphenyl, benzyl, —CH2CH2-phenyl, pyridinyl, —C(O)OC1-3alkyl, and/or —CH2OCH3; and wherein each of said heterocyclyl groups is substituted with zero to three substituents independently selected from C1-3alkyl, —OH, —NH2, phenyl, methylphenyl, benzyl, —CH2CH2-phenyl, pyridinyl, —C(O)OC1-3alkyl, ═O, and/or —CH2OCH3.