Abstract:
:We previously reported 2-[2-(4-tert-butylphenyl)ethyl]-N-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide 2 as on orally available monoacylglycerol acyltransferase 2 (MGAT2) inhibitor which exhibited an in vivo efficacy at an oral dose of 100 mg/kg in a mouse oral lipid tolerance test. Further optimization of compound 2 to improve the intrinsic potency culminated in the identification of compound 11. Compound 11 showed a >50-fold lower IC50 against human MGAT2 enzyme than 2. Oral administration of 11 at a dose of 3 mg/kg in the oral lipid tolerance test resulted in significant suppression of triglyceride synthesis.
journal_name
Chem Pharm Bull (Tokyo)journal_title
Chemical & pharmaceutical bulletinauthors
Busujima T,Tanaka H,Iwakiri K,Shirasaki Y,Munetomo E,Saito M,Masuko A,Kitano K,Io F,Kato K,Kamigaso S,Nozoe A,Sato Ndoi
10.1248/cpb.c15-00803subject
Has Abstractpub_date
2016-01-01 00:00:00pages
228-38issue
3eissn
0009-2363issn
1347-5223journal_volume
64pub_type
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