Synthesis and biological evaluation of anthranilamide-based non-peptide mimetics of ω-conotoxin GVIA

Non-peptide mimetics based on an anthranilamide 'scaffold' possessing fragments that mimic Lys2, Tyr13 and Arg17 in omega-conotoxin GVIA have been prepared. Compounds were assayed for binding to the voltage-gated calcium channels Ca(v)2.2 ('N-type') and Ca(v)2.1 'P/Q-type') in rat brain. The primary synthetic target, 2-(6-amino-hexanoylamino)-5-(3-guanidino-propoxy)-N-[4-(4-hydroxyphenoxy)phenyll -benzamide (2a), exhibited low mu M binding to Ca(v)2.2 and was more than 30-fold selective for Ca(v)2.2 over Cav2. 1. Crown Copyright (c) 2006 Published by Elsevier Ltd. All rights reserved.