Discovery of potent and orally bioavailable heterocycle-based cannabinoid CB1 receptor agonists

被引：5

作者：

Kiyoi, Takao ^{[1
]}

Adam, Julia M. ^{[1
]}

Clark, John K. ^{[1
]}

Davies, Keneth ^{[1
]}

Easson, Anna-Marie ^{[1
]}

Edwards, Darren ^{[1
]}

Feilden, Helen ^{[1
]}

Fields, Ruth ^{[1
]}

Francis, Stuart ^{[1
]}

Jeremiah, Fiona ^{[1
]}

McArthur, Duncan ^{[1
]}

Morrison, Angus J. ^{[1
]}

Prosser, Alan ^{[1
]}

Ratcliffe, Paul D. ^{[1
]}

Schulz, Jurgen ^{[1
]}

Wishart, Grant ^{[1
]}

Baker, James ^{[2
]}

Campbell, Robert ^{[2
]}

Cottney, Jean E. ^{[2
]}

Deehan, Maureen ^{[2
]}

Epemolu, Ola ^{[2
]}

Evans, Louise ^{[2
]}

机构：

[1] Merck Res Labs, Dept Chem, MSD, Newhouse ML1 5SH, Lanark, Scotland

[2] Merck Res Labs, Dept Pharmacol, MSD, Newhouse ML1 5SH, Lanark, Scotland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 06期

关键词：

Cannabinoid; CB1 receptor agonist; Oral bioavailability; NITRILE SULFIDES; DRUG DISCOVERY; PAIN; INDOLE-3-CARBOXAMIDES; GENERATION; DESIGN; MODELS;

D O I：

10.1016/j.bmcl.2011.01.082

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel 3-(1H-indol-3-yl)-1,2,4-oxadiazoles and -thiadiazoles were synthesized and found to be potent CB1 cannabinoid receptor agonists. The oral bioavailability of these compounds could be dramatically improved by optimization studies of the side chains attached to the indole and oxadiazole cores, leading to identification of a CB1 receptor agonist with good oral activity in a range of preclinical models of antinociception and antihyperalgesia. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：1748 / 1753

页数：6

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