Orally active C-6 heteroaryl- and heterocyclyl-substituted imidazo[1,2-a]pyridine acid pump antagonists (APAs)
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、Hui-Xian Seow、David Spalding、Andrew K. Takle
DOI:10.1016/j.bmcl.2009.04.127
日期:2009.7
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 pro. le. 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. (C) 2009 Elsevier Ltd. All rights reserved.