2-Sulfonamidopyridine C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists. Issue 6 (15th March 2016)

• Record Type: Journal Article
• Authors: Ann, Jihyae; Ki, Yooran; Yoon, Suyoung; Kim, Myeong Seop; Lee, Jung-Un; Kim, Changhoon; Lee, Sunho; Jung, Aeran; Baek, Jisoo; Hong, Sunhye; Choi, Sun; Pearce, Larry V.; Esch, Timothy E.; Turcios, Noe A.; Lewin, Nancy E.; Ogunjirin, Adebowale E.; Herold, Brienna K.A.; McCall, Anna K.; Blumberg, Peter M.; Lee, Jeewoo
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 6(2016)
• Page Start: 1231
• Page End: 1240
• Publication Date: 2016-03-15
• Subjects: Vanilloid receptor 1 -- TRPV1 antagonists -- Analgesic; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.01.051
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: A series of 2-sulfonamidopyridine C-region derivatives of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamide were investigated as h TRPV1 ligands. Systematic modification on the 2-sulfonamido group provided highly potent TRPV1 antagonists. The N -benzyl phenylsulfonamide derivatives12 and23 in particular showed higher affinities than that of lead compound1 . Compound12 exhibited strong analgesic activity in the formalin pain model. Docking analysis of its chiral S -form12 S in our h TRPV1 homology model indicated that its high affinity might arise from additional hydrophobic interactions not present in lead compound1 S .