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

被引：15

作者：

Hong, Dong Jin ^{[1
,2
]}

Jung, Seung Hyun ^{[2
]}

Kim, Jisook ^{[2
]}

Jung, Danbee ^{[1
]}

Ahn, Young Gil ^{[2
]}

Suh, Kwee Hyun ^{[2
]}

Min, Kyung Hoon ^{[1
]}

机构：

[1] Chung Ang Univ, Coll Pharm, Seoul, South Korea

[2] Hanmi Pharm Co Ltd, Hanmi Res Ctr, Hwaseong Si, Gyeonggi Do, South Korea

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2020年 / 35卷 / 01期

关键词：

DGAT-1; obesity; small molecules; thienopyrimidine; type; 2; diabetes; OBESITY; DISCOVERY; POTENT; TRIGLYCERIDES; RESISTANCE; ESTERS;

D O I：

10.1080/14756366.2019.1693555

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：227 / 234

页数：8

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