Accelerating the discovery of DGAT1 inhibitors through the application of parallel medicinal chemistry (PMC). Issue 11 (1st June 2019)

• Record Type: Journal Article
• Authors: Yu, Yang; Wu, Zhicai; Shi, Zhi-Cai; He, Shuwen; Lai, Zhong; Cernak, Timothy A.; Vachal, Petr; Liu, Min; Liu, Jian; Hong, Qingmei; Jian, Tianying; Guiadeen, Deodial; Krikorian, Arto; Sperbeck, Donald M.; Verras, Andreas; Sonatore, Lisa M.; Murphy, Beth A.; Wiltsie, Judyann; Chung, Christine C.; Gorski, Judith N.; Liu, Jinqi; Xiao, Jianying; Wolff, Michael; Tong, Sharon X.; Madeira, Maria; Karanam, Bindhu V.; Shen, Dong-Ming; Balkovec, James M.; De Vita, Robert J.; Pinto, Shirly; Nargund, Ravi P.;
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 11(2019)
• Page Start: 1380
• Page End: 1385
• Publication Date: 2019-06-01
• Subjects: Parallel medicinal chemistry -- High throughput purification -- DGAT1 inhibitor -- Triglyceride -- Benzimidazole -- ACAT1 -- A2A receptor -- Cyclohexane acetic acid -- Lipid tolerance test -- Pharmacokinetics; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.03.039
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: The parallel medicinal chemistry (PMC) was effectively applied to accelerate the optimization of diacylglycerol O-acyltransferase I (DGAT-1) inhibitors. Through a highly collaborative and iterative library design, synthesis and testing, a benzimidazole lead was rapidly and systematically advanced to a highly potent, selective and bioavailable DGAT1 inhibitor with the potential for further development.