Identification of 2-[2-(4-<i>tert</i>-Butylphenyl)ethyl]-<i>N</i>-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide as an Orally Active MGAT2 Inhibitor
-
- Busujima Tsuyoshi
- Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Tanaka Hiroaki
- Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Iwakiri Kanako
- Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Shirasaki Yoshihisa
- Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Munetomo Eiji
- Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Saito Masako
- Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Masuko Aiko
- Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Kitano Kiyokazu
- Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Io Fusayo
- Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Kato Koji
- Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Kamigaso Shunsuke
- Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Nozoe Akiko
- Pharmaceutical Science Laboratories, Taisho Pharmaceutical Co., Ltd.
-
- Sato Nagaaki
- Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd.
Bibliographic Information
- Other Title
-
- Identification of 2-[2-(4-tert-Butylphenyl)ethyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide as an Orally Active MGAT2 Inhibitor
Search this article
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
-
- Chemical and Pharmaceutical Bulletin
-
Chemical and Pharmaceutical Bulletin 64 (3), 228-238, 2016
The Pharmaceutical Society of Japan
- Tweet
Keywords
Details 詳細情報について
-
- CRID
- 1390001204177669120
-
- NII Article ID
- 130005131597
-
- NII Book ID
- AA00602100
-
- ISSN
- 13475223
- 00092363
-
- NDL BIB ID
- 027133448
-
- PubMed
- 26936050
-
- Text Lang
- en
-
- Data Source
-
- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
-
- Abstract License Flag
- Disallowed