Substituted 2,3-dihydro-1<i>H</i>-inden-1-one retinoic acid-related orphan nuclear receptor antagonists for treating multiple sclerosis

摘要

The present invention is directed to compounds, their synthesis, and their use as antagonists, inverse agonists, modulators and or inhibitors of the Retinoic acid-related orphan nuclear receptor γt (RORγt)/RORγ. The compounds of the present invention are useful for modulating RORγt)/RORγ activity and for treating diseases or conditions mediated by RORγt)/RORγ such as for example, disease states associated with immunopathology of human autoimmune diseases such as Multiple Sclerosis (MS), Rheumatoid Arthritis (RA), Inflammatory Colitis, Psoriasis, COPD, Pain, Obesity, Diabetes, Dyslipidemia, Osteoporosis, Asthma, Neurodegenerative diseases and Cancer.

主权项

1. A compound according to Formula I:or pharmaceutically acceptable salts thereof, wherein:
X is O R1 isor
R1 is C1-4alkyl optionally substituted with 1-6 independent halo substituents; or R1 is phenyl, pyridinyl, or pyrazolyl, each optionally substituted with 1-5 independent halo, trifluoromethyl, (trifluoromethyl)thio, trifluoromethoxy, 1,1,1,3,3,3,-hexafluoro-2-hydroxypropan-2-yl,substituents;
m is 0 or 1; the dotted line indicates an optional double bond when m=1; R2 is halo, —OH, —CN, —OCH3, —O—S(O)2CH2CH3, or phenyl optionally substituted with 0-5 independent halo, trifluoromethoxy substituents; R1 is n is 2 or 3 carbon chain; and R4 is H, OH, OCH3, or —O—S(O)2CH2CH3.