DSpace at EWHA: 2-Sulfonamidopyridine C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists

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2-Sulfonamidopyridine C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists

Title: 2-Sulfonamidopyridine C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists

Authors: Ann J.; Ki Y.; Yoon S.; Kim M.S.; Lee J.-U.; Kim C.; Lee S.; Jung A.; Baek J.; Hong S.; Choi S.; Pearce L.V.; Esch T.E.; Turcios N.A.; Lewin N.E.; Ogunjirin A.E.; Herold B.K.A.; McCall A.K.; Blumberg P.M.; Lee J.

Citation: Bioorganic and Medicinal Chemistry vol. 24, no. 6, pp. 1231 - 1240

Abstract: A series of 2-sulfonamidopyridine C-region derivatives of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamide were investigated as hTRPV1 ligands. Systematic modification on the 2-sulfonamido group provided highly potent TRPV1 antagonists. The N-benzyl phenylsulfonamide derivatives 12 and 23 in particular showed higher affinities than that of lead compound 1. Compound 12 exhibited strong analgesic activity in the formalin pain model. Docking analysis of its chiral S-form 12S in our hTRPV1 homology model indicated that its high affinity might arise from additional hydrophobic interactions not present in lead compound 1S. © 2016 Elsevier Ltd. All rights reserved.