Solid-Phase Synthesis of New Trp(Nps)-Containing Dipeptide Derivatives as TRPV1 Channel Blockers 英文参考文献.docVIP

Molecules 2010, 15, 4924-4933; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Solid-Phase Synthesis of New Trp(Nps)-Containing Dipeptide Derivatives as TRPV1 Channel Blockers Ma Jesús Pérez de Vega 1, Ma Teresa García-López 1, Laura Zaccaro 2, Miriam Royo 2, Fernando Albericio 3,4,5, Asia Fernández-Carvajal 6, Antonio Ferrer-Montiel 6 and Rosario González-Mu?iz 1,* 1 Instituto de Química Médica, CSIC, Juan de la Cierva, 3, 28006 Madrid, Spain 2 Combinatorial Chemistry Unit, Barcelona Science Park, University of Barcelona, Barcelona 08028, Spain 3 Institute for Research in Biomedicine, Barcelona Science Park, University of Barcelona, Barcelona 08028, Spain 4 CIBER-BBN, Networking Centre on Bioengineering Biomaterials and Nanomedicine, Barcelona 08028, Spain 5 Department of Organic Chemistry, University of Barcelona, Barcelona 08028, Spain 6 IBMC-UMH, Ed. Torregaitán, Av. de la Universidad s/n, 03202 Elche, Spain * Author to whom correspondence should be addressed; E-Mail: rosario.gonzalezmuniz@iqm.csic.es; Tel.: +34-915-622-900; Fax: +34-915-644-853. Received: 11 June 2010; in revised form: 14 July 2010 / Accepted: 15 July 2010 / Published: 15 July 2010 Abstract: Trp(Nps)-Lys-NH2 derivatives, bearing alkyl or guanidine groups either at the N–terminus or on the Lys side-chain or at both positions were conveniently prepared on solid-phase and evaluated as TRPV1 channel antagonists. Keywords: solid-phase; Trp(Nps) dipeptides; TRPV1 channel blockers 1. Introduction TRPV1 (Transient Receptor Potential Vanilloid 1) is a non-selective, Ca2+ preferring, ion channel, activated by temperatures higher than 42 oC, acidic pH, vanilloids such as capsaicin, and the endogenous cannabinoid receptor ligand anandamide [1]. TRPV1 expression is up-regulated in a number of painful disorders, including chronic, neuropathic and acute inflammatory pain, and  Molecules 2010, 15