Orally active C-6 heteroaryl- and heterocyclyl-substituted imidazo[1,2-a

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• 作者：Nick Bailey ; Mark J. Bamford ; Delphine Brissy ; Joanna Brookfield ; Emmanuel Demont ; Richard Elliott ; Neil Garton ; Irene Farre-Gutierrez ; Thomas Hayhow ; Gail Hutley ; Antoinette Naylor ; Terry A. Panchal
• 关键词：Acid pump antagonist ; Potassium competitive acid blocker ; Imidazo[1 ; 2-a]pyridine
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：1 July 2009
• 年：2009
• 卷：19
• 期：13
• 页码：3602-3606
• 全文大小：310 K

文摘

Acid pump antagonists (APAs) such as the imidazo[1,2-a]pyridine AZD-0865 2 have proven efficacious at low oral doses in acid related gastric disorders. Herein we describe some of the broader SAR in this class of molecule and detail the discovery of an imidazo[1,2-a]pyridine 15 which has excellent efficacy in animal models of gastric acid secretion following oral administration, as well as a good overall developability profile. The discovery strategy focuses on use of heteroaryl and heterocyclic substituents at the C-6 position and optimization of developability characteristics through modulation of global physico-chemical properties.