SUBSTITUTED TRICYCLIC ACID DERIVATIVES AS S1P1 RECEPTOR AGONISTS USEFUL IN THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISORDERS

摘要

The present invention relates to certain substituted tricyclic acid derivatives of Formula (I) and pharmaceutically acceptable salts thereof, which exhibit useful pharmacological properties, for example, as agonists of the S1P1 receptor. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the treatment of S1P1-associated disorders, for example, psoriasis, rheumatoid arthritis, Crohn's disease, transplant rejection, multiple sclerosis, systemic lupus erythematosus, ulcerative colitis, type I diabetes, acne, myocardial ischemia-reperfusion injury, hypertensive nephropathy, glomerulosclerosis, gastritis, polymyositis, thyroiditis, vitiligo, hepatitis, biliary cirrhosis, microbial infections and associated diseases, viral infections and associated diseases, diseases and disorders mediated by lymphocytes, auto immune diseases, inflammatory diseases, and cancer.;

主权项

1. A compound selected from compounds of Formula (I) and pharmaceutically acceptable salts, solvates, and hydrates thereof: wherein:
m is 1 or 2;n is 1 or 2;Y is N or CR1;Z is N or CR4;W is N or CR5;Ra is H or C1-C6 alkyl;R1, R2, R3, and R4 are each independently selected from the group consisting of H, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkylsulfonyl, C1-C6 alkylthio, carboxamide, cyano, C3-C7 cycloalkoxy, C3-C7 cycloalkyl, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heteroaryl, and heterocyclyl, wherein said C1-C6 alkyl and C1-C6 alkoxy are each optionally substituted with one C3-C7 cycloalkyl group; andR5 is selected from the group consisting of H, C1-C6 alkyl, C1-C6 alkylsulfonyl, cyano, C3-C7 cycloalkyl, C1-C6 haloalkyl, halogen, heteroaryl, and heterocyclyl.