pmid: 31752563,   nlmid 101150203,  doi:10.1080/14756366.2019.1693555

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


Hong, Dong Jin Jung, Seung Hyun Kim, Jisook Jung, Danbee Ahn, Young Gil Suh, Kwee Hyun Min, Kyung Hoon

Vol. 35, Issue 35, Dec.2020

Journal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem),  ISSN 1475-6374

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 showed potent and selective inhibitory activity against DGAT-1 in SF9 cells. In addition, had an acceptable pharmacokinetic profile and accumulated mainly in the small intestine and liver. Oral administration of led to a significant reduction in plasma triacylglycerol level during an oral lipid tolerance test (OLTT) in murine and canine models. Taken together, is a high-quality candidate that deserves further investigation.


MESH Headings


Article Keywords

DGAT-1 | obesity | small molecules | thienopyrimidine | type 2 diabetes |


Chemical

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