Discovery of microsomal triglyceride transfer protein (MTP) inhibitors with potential for decreased active metabolite load compared to dirlotapide

…, JA Bartlett, P Bertinato, AJ Bessire, J Cosgrove…

Index: Robinson, Ralph P.; Bartlett, Jeremy A.; Bertinato, Peter; Bessire, Andrew J.; Cosgrove, Judith; Foley, Patrick M.; Manion, Tara B.; Minich, Martha L.; Ramos, Brenda; Reese, Matthew R.; Schmahai, Theodore J.; Swick, Andrew G.; Tess, David A.; Vaz, Alfin; Wolford, Angela Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 14 p. 4150 - 4154

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Citation Number: 13

Abstract

Abstract Analogues related to dirlotapide (1), a gut-selective inhibitor of microsomal triglyceride transfer protein (MTP) were prepared with the goal of further reducing the potential for unwanted liver MTP inhibition and associated side-effects. Compounds were designed to decrease active metabolite load: reducing MTP activity of likely human metabolites and increasing metabolite clearance to reduce exposure. Introduction of 4′- ...