Discovery of 1-[4-(3-Chlorophenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridin-7-yl]-1-morpholin-4-ylmethanone (GSK554418A), a Brain Penetrant 5-Azaindole CB2 Agonist for the Treat

详细信息    查看全文

• 作者：Gerard M. P. Giblin ; Andrew Billinton ; Michael Briggs ; Andrew J. Brown ; Iain P. Chessell ; Nick M. Clayton ; Andrew J. Eatherton ; Paul Goldsmith ; Carl Haslam ; Matthew R. Johnson ; William L. Mitchell ; Al
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：October 8, 2009
• 年：2009
• 卷：52
• 期：19
• 页码：5785-5788
• 全文大小：747K
• 年卷期：v.52,no.19(October 8, 2009)
• ISSN：1520-4804

文摘

We report the synthesis and SAR of a series of novel azaindole CB₂ agonists. 6-Azaindole 18 showed activity in an acute pain model but was inactive in a chronic model. 18 is a Pgp substrate with low brain penetration. The template was redesigned, and the resulting 5-azaindole 36 was a potent CB₂ agonist with high CNS penetration. This compound was efficacious in the acute model and the chronic joint pain model.