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

被引：27

作者：

Baell, Jonathan B.

Duggan, Peter J.

Forsyth, Stewart A.

Lewis, Richard J.

Lok, Y. Phei

Schroeder, Christina I.

Shepherd, Nicholas E.

机构：

[1] Biomol Res Inst, Parkville, Vic 3052, Australia

[2] Walter & Eliza Hall Inst Med Res, Biotechnol Ctr, Struct Biol Chem Grp, Bundoora, Vic 3086, Australia

[3] Monash Univ, Sch Chem, Clayton, Vic 3800, Australia

[4] CSIRO Mol & Hlth Technol, Clayton, Vic 3169, Australia

[5] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia

来源：

TETRAHEDRON | 2006年 / 62卷 / 31期

基金：

英国医学研究理事会;

关键词：

omega-conotoxin; mimetic; Ca(v)2.2 ('N-type') calcium channel blocker;

D O I：

10.1016/j.tet.2006.05.041

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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.

引用

页码：7284 / 7292

页数：9

共 21 条

[1] SYNTHESIS OF NITROPHENOLS [J].