Design and Synthesis of Indole-Based Peptoids as Potent Noncompetitive Antagonists of Transient Receptor Potential Vanilloid 1
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- 作者：Martina Quintanar-Audelo ; Asia Ferná ; ndez-Carvajal ; Wim Van Den Nest ; Cristina Carreñ ; o ; Antonio Ferrer-Montiel ; Fernando Albericio
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：November 29, 2007
- 年：2007
- 卷：50
- 期：24
- 页码：6133 - 6143
- 全文大小：351K
- 年卷期：v.50,no.24(November 29, 2007)
- ISSN：1520-4804
文摘
The vanilloid receptor subunit 1, or transient receptor potential vanilloid 1 (TRPV1), integrates physicaland chemical stimuli in the peripheral nervous system, playing a key role in inflammatory pain. Identificationof potent TRPV1 antagonists is thus an important goal of current neuropharmacology. Herein, we describethe solid-phase synthesis of a series of indole-based peptoids (N-alkylglycines) and the biological activityof the peptoids as novel TRPV1 antagonists. The potency and selectivity of the compounds were determinedby electrophysiological recordings in Xenopus oocytes. The most potent and selective noncompetitive TRPV1antagonist of the series, compound 7, represents an interesting pharmacophoric structure for analgesic leadoptimization.