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
| Autor: | Yoshihisa Shirasaki, Eiji Munetomo, Naoto Osaki, Kiyokazu Kitano, Hiroaki Tanaka, Nagaaki Sato, Toshiya Minagawa, Tsuyoshi Busujima, Masako Saito, Koji Yoshida |
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| Rok vydání: | 2015 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Pharmaceutical Science N-Acetylglucosaminyltransferases Biochemistry Monoacylglycerol acyltransferase Mice Structure-Activity Relationship chemistry.chemical_compound Tetrahydroisoquinolines Diabetes mellitus Drug Discovery Diabetes Mellitus medicine Animals Humans Structure–activity relationship Potency Obesity Solubility Molecular Biology IC50 chemistry.chemical_classification Sulfonamides Chemistry Tetrahydroisoquinoline Organic Chemistry medicine.disease Sulfonamide Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry. 23:5922-5931 |
| ISSN: | 0968-0896 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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