title: Design and synthesis of indole-based peptoids as potent noncompetitive antagonists of transient receptor potential vanilloid 1.
abstract: The vanilloid receptor subunit 1, or transient receptor potential vanilloid 1 (TRPV1), integrates physical and chemical stimuli in the peripheral nervous system, playing a key role in inflammatory pain. Identification of potent TRPV1 antagonists is thus an important goal of current neuropharmacology. Herein, we describe the solid-phase synthesis of a series of indole-based peptoids (N-alkylglycines) and the biological activity of the peptoids as novel TRPV1 antagonists. The potency and selectivity of the compounds were determined by electrophysiological recordings in Xenopus oocytes. The most potent and selective noncompetitive TRPV1 antagonist of the series, compound 7, represents an interesting pharmacophoric structure for analgesic lead optimization.
authors.affiliation: Department of Organic Chemistry, IRB Barcelona, Barcelona Science Park, University of Barcelona, Spain.
authors.forename: Martina
authors.initials: M
authors.lastname: Quintanar-Audelo
authors.forename: Asia
authors.initials: A
authors.lastname: Fernández-Carvajal
authors.forename: Wim
authors.initials: W
authors.lastname: Van Den Nest
authors.forename: Cristina
authors.initials: C
authors.lastname: Carreño
authors.forename: Antonio
authors.initials: A
authors.lastname: Ferrer-Montiel
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D015195:Drug Design; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D034444:Peptoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D014981:Xenopus
chemical_list: D000700:Analgesics; D007211:Indoles; D009842:Oligopeptides; D034444:Peptoids; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C526818:arginyl-(N-(2,4-dichlorophenethyl)glycyl)-N-(2-(indol-3-yl)ethyl)glycinamide