N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4, 5, 6, 7-tetrahydrobenzofuran-2-sulfonamide derivatives and related compounds as nlpr3 modulators for the treatment of multiple sclerosis (ms)

Abstract

Described herein are N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl) carbamoyl)-4,5,6,7-tetrahydrobenzofuran-2-sulfonamide derivatives and related compounds of formula (I) wherein R1 is formulae (II), (III), (IV), (V), (VI), (VII), (VIII) or (IX) and R2 is formulae (X) or (XI) as NLRP3 (pyrin domain-containing protein 3) modulators for the treatment of e.g. metabolic diseases (e.g. type 2 diabetes or obesity), liver diseases (e.g. NAFLD or cirrhosis), lung diseases (e.g. asthma or CORD), central nervous system diseases (e.g. Alzheimer's disease or multiple sclerosis), inflammatory or autoimmune diseases (e.g. rheumatoid arthritis or psoriasis), cardiovascular diseases (e.g. atherosclerosis or stroke). The present description discloses the synthesis and characterization of exemplary compounds as well as pharmacological data thereof. An exemplary compound is e.g. N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl) carbamoyl)-4-hydroxy-4-methyl-4,5,6,7-tetrahydrobenzofuran-2-sulfonamide (Example 1; compound (5)).