Evaluation of basic, heterocyclic ring systems as templates for use as potassium competitive acid blockers (pCABs)
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- 作者：Terry Panchal ; Nick Bailey ; Mark Bamford ; Emmanuel Demont ; Richard Elliott ; Irene Farre-Gutierrez ; Neil Garton ; Thomas Hayhow ; Gail Hutley ; Antoinette Naylor
- 关键词：Potassium competitive acid blockers ; APA ; Acid secretion ; Acid pump antagonists ; 1H-Pyrrolo[2 ; 3-c]pyridine
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2009
- 出版时间：1 December 2009
- 年：2009
- 卷：19
- 期：23
- 页码：6813-6817
- 全文大小：451 K
文摘
A variety of basic, heterocyclic templates has been reported as potassium-competitive, acid pump antagonists. Herein, we report a comparison of potencies of these templates and others to establish which offers the best start point for further systematic optimisation. Modifications were carried out to improve the developability profile of the more potent 1H-pyrrolo[2,3-c]pyridine template, affording molecules with improved overall in vitro characteristics versus the reported clinical candidate AR-H047108, and comparable to the clinically efficacious AZD-0865.