Identification And Optimization Of Tertiary Sulfonamides As Rorc Inverse Agonists

Benjamin P. Fauber,Olivier Rene,Gladys De Leon Boenig,Brenda Burton,Yuzhong Deng,Celine Eidenschenk,Christine Everett,Alberto Gobbi,Julie Hawkins,Sarah G. Hymowitz,Adam R. Johnson,Hank La,Marya Liimatta, Peter Lockey, Maxine Norman,Wenjun Ouyang,Weiru Wang,Harvey Wong

Medicinal Chemistry（2014）

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摘要

S a nuclear receptor compound subset in a RORc biochemical binding assay revealed a benzylic tertiary sulfonamide hit. Using structure-based drug design principles, we created compounds with improved RORc biochemical inverse agonist activity and cellular potencies ( 100-fold) and favorable physiochemical properties.

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