Identification of 2-oxo-N-(phenylmethyl)-4-imidazolidinecarboxamide antagonists of the P2X7 receptor

被引：32

作者：

Abberley, Lee ^{[1
]}

Bebius, Aude ^{[1
]}

Beswick, Paul J. ^{[1
]}

Billinton, Andy ^{[1
]}

Collis, Katharine L. ^{[1
]}

Dean, David K. ^{[1
]}

Fonfria, Elena ^{[1
]}

Gleave, Robert J. ^{[1
]}

Medhurst, Stephen J. ^{[1
]}

Michel, Anton D. ^{[1
]}

Moses, Andrew P. ^{[1
]}

Patel, Sadhana ^{[1
]}

Roman, Shilina A. ^{[1
]}

Scoccitti, Tiziana ^{[1
]}

Smith, Beverley ^{[1
]}

Steadman, Jon G. A. ^{[1
]}

Walter, Daryl S. ^{[1
]}

机构：

[1] GlaxoSmithKline, Neurosci Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 22期

关键词：

P2X7; Antagonist; Pain; PAIN; DISCOVERY; SERIES; MODEL;

D O I：

10.1016/j.bmcl.2010.09.101

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A backup molecule to compound 2 was sought by targeting the most likely metabolically vulnerable site in this molecule. Compound 18 was subsequently identified as a potent P2X(7) antagonist with very low in vivo clearance and high oral bioavailability in all species examined. Some evidence to support the role of P2X(7) in the etiology of pain is also presented. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：6370 / 6374

页数：5