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Identification of 2-[2-(4-tert-butylphenyl)ethyl]-N-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide (29) as an orally available MGAT2 inhibitor.

Abstract：

:MGAT2 (monoacylglycerol acyltransferase 2) is expected to be an attractive target for the drug treatment of obesity, diabetes, and other disease. We describe our exploration and structure-activity relationship (SAR) study of 2,3-dihydro-1H-isoindole-5-sulfonamide derivatives. In this study, we identified 29 as an orally available inhibitor of MGAT2 through optimization especially in terms of solubility. This compound exhibited moderate potency in the enzyme inhibitory assay (IC50 = 1522 nM) and significant suppression of fat absorption (57% inhibition) in mice oral lipid tolerance test.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Busujima T,Tanaka H,Shirasaki Y,Munetomo E,Saito M,Kitano K,Minagawa T,Yoshida K,Osaki N,Sato N

doi

10.1016/j.bmc.2015.06.065

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

5922-31

issue

17

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(15)00559-3

journal_volume

23

pub_type

杂志文章

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