当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Discovery and optimization of adamantane carboxylic acid derivatives as potent diacylglycerol acyltransferase 1 inhibitors for the potential treatment of obesity and diabetes.

Discovery and optimization of adamantane carboxylic acid derivatives as potent diacylglycerol acyltransferase 1 inhibitors for the potential treatment of obesity and diabetes.

Abstract：

:We have developed a series of adamantane carboxylic acid derivatives exhibiting potent diacylglycerol acyltransferase 1 (DGAT1) inhibitory activities. Optimization of the series led to the discovery of E-adamantane carboxylic acid compound 43c, which showed excellent in vitro activity with an IC50 value of 5 nM against human and mouse DGAT1, also good druggability as well as microsomal stability and safety profiles such as hERG, CYP and cytotoxicity. Compound 43c significantly reduced plasma triglyceride levels in vivo (in rodents and zebrafish) and also showed bodyweight gain reduction and glucose area under curve (AUC) lowering efficacy in diet-induced obesity (DIO) mice.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Pagire SH,Pagire HS,Lee GB,Han SJ,Kwak HJ,Kim JY,Kim KY,Rhee SD,Ryu JI,Song JS,Bae MA,Park MJ,Kim D,Lee DH,Ahn JH

doi

10.1016/j.ejmech.2015.06.043

subject

Has Abstract

pub_date

2015-08-28 00:00:00

pages

716-35

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(15)30118-5

journal_volume

101

pub_type

杂志文章

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