1445902-92-0

Upstream product

• 13889-98-0 N-acetylpiperidine 
• 439814-87-6 4-bromo-1-(dimethoxymethyl)-2-fluorobenzene 

Downstream Products

• 1445901-81-4 N-(4-(4-acetylpiperazin-1-yl)-2-fluorobenzyl)-3,5-dichloro-N-cyclobutylbenzenesulfonamide 
• 1445901-02-9 N-[4-(4-acetyl-piperazin-1-yl)-2-fluoro-benzyl]-4-tert-butyl-N-cyclobutyl-benzenesulfonamide 
• 1445902-01-1 N-[4-(4-acetyl-piperazin-1-yl)-2-fluoro-benzyl]-N-cyclobutyl-4-trifluoromethyl-benzenesulfonamide 
• 1445901-11-0 N-[4-(4-acetylpiperazin-1-yl)-2-fluorobenzyl]-N-cyclobutyl-4-trifluoromethoxy-benzenesulfonamide 
• 1445908-80-4 N-[4-(4-acetyl-piperazin-1-yl)-2-fluoro-benzyl]-N-cyclobutyl-4-difluoromethoxy-benzenesulfonamide 
• 1445901-24-5 N-[4-(4-acetylpiperazin-1-yl)-2-fluorobenzyl]-2,4-dichloro-N-cyclobutylbenzenesulfonamide 
• 1445901-31-4 N-[4-(4-acetylpiperazin-1-yl)-2-fluorobenzyl]-N-cyclobutyl-4-methoxybenzenesulfonamide 
• 1445901-51-8 N-[4-(4-acetylpiperazin-1-yl)-2-fluorobenzyl]-4-cyano-N-cyclobutylbenzenesulfonamide 
• 1445901-15-4 N-[4-(4-acetylpiperazin-1-yl)-2-fluorobenzyl]-N-cyclobutyl-3-methoxybenzenesulfonamide 
• 1445902-00-0 N-[4-(4-acetyl-piperazin-1-yl)-2-fluoro-benzyl]-N-cyclobutyl-3,5-difluorobenzenesulfonamide 
• 1445901-64-3 N-[4-(4-acetyl-piperazin-1-yl)-2-fluorobenzyl]-N-cyclobutyl-1-(3,5-dichloro-phenyl)methanesulfonamide 
• 1445901-70-1 N-[4-(4-acetyl-piperazin-1-yl)-2-fluoro-benzyl]-1-(4-chloro-phenyl)-N-cyclobutylmethanesulfonamide 
• 1445902-08-8 N-[4-(4-acetyl-piperazin-1-yl)-2-fluoro-benzyl]-4-chloro-N-cyclobutylbenzenesulfonamide 
• 1445901-73-4 N-[4-(4-acetyl-piperazin-1-yl)-2-fluoro-benzyl]-N-cyclobutyl-1-(3-chlorophenyl)-methanesulfonamide 

Relevant academic research and scientific papers

Minor structural change to tertiary sulfonamide RORC ligands led to opposite mechanisms of action

A minor structural change to tertiary sulfonamide RORc ligands led to distinct mechanisms of action. Co-crystal structures of two compounds revealed mechanistically consistent protein conformational changes. Optimized phenylsulfonamides were identified as RORc agonists while benzylsulfonamides exhibited potent inverse agonist activity. Compounds behaving as agonists in our biochemical assay also gave rise to an increased production of IL-17 in human PBMCs whereas inverse agonists led to significant suppression of IL-17 under the same assay conditions. The most potent inverse agonist compound showed >180-fold selectivity over the ROR isoforms as well as all other nuclear receptors that were profiled.

BENZYL SULFONAMIDE DERIVATIVES AS RORc MODULATORS

Compounds of the formula (I) or pharmaceutically acceptable salts thereof, wherein m, n, A, X1, X2, X3, X4, R1, R2, R3a, R3b, R4a and R4b are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of inflammatory diseases such as arthritis.