title: α-Aryl pyrrolidine sulfonamides as TRPA1 antagonists.
abstract: A series of α-aryl pyrrolidine sulfonamide TRPA1 antagonists were advanced from an HTS hit to compounds that were stable in liver microsomes with retention of TRPA1 potency. Metabolite identification studies and physicochemical properties were utilized as a strategy for compound design. These compounds serve as starting points for further compound optimization.
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States.
authors.forename: Vishal A
authors.initials: VA
authors.lastname: Verma
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States.
authors.forename: Daniel G M
authors.initials: DGM
authors.lastname: Shore
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States.
authors.forename: Huifen
authors.initials: H
authors.lastname: Chen
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States.
authors.forename: Steven
authors.initials: S
authors.lastname: Do
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States.
authors.forename: David H
authors.initials: DH
authors.lastname: Hackos
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States.
authors.forename: Aleks
authors.initials: A
authors.lastname: Kolesnikov
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Lyssikatos
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Tay
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States.
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Estrada
mesh_terms: D000818:Animals; D015220:Calcium Channels; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology*; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors*
chemical_list: D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D011759:Pyrrolidines; D013449:Sulfonamides; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels
keywords: Ion channel; Metabolic stability; TRPA1