Synthesis and biological evaluation of novel thienopyrimidine derivatives as diacylglycerol acyltransferase 1 (DGAT-1) inhibitors. (1st January 2020)

• Record Type: Journal Article
• Authors: Hong, Dong Jin; Jung, Seung Hyun; Kim, Jisook; Jung, Danbee; Ahn, Young Gil; Suh, Kwee Hyun; Min, Kyung Hoon
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 35:Number 1(2020)
• Page Start: 227
• Page End: 234
• Publication Date: 2020-01-01
• Subjects: DGAT-1 -- obesity -- small molecules -- thienopyrimidine -- type 2 diabetes; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2019.1693555
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: A novel series of thieno[3, 2- d ]pyrimidine derivatives were synthesised and their inhibitory effects against diacylglycerol acyltransferase 1 (DGAT-1) were assessed. cis-Isomer 17a showed potent and selective inhibitory activity against DGAT-1 in SF9 cells. In addition, 17a had an acceptable pharmacokinetic profile and accumulated mainly in the small intestine and liver. Oral administration of 17a led to a significant reduction in plasma triacylglycerol level during an oral lipid tolerance test (OLTT) in murine and canine models. Taken together, 17a is a high-quality candidate that deserves further investigation.