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

• 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.

書誌事項

タイトル別名

• 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

抄録

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.

収録刊行物

• ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ

  ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ 64 (3), 228-238, 2016

  公益社団法人 日本薬学会

キーワード

• monoacylglycerol acyltransferase 2
• fat absorption
• oral lipid tolerance test
• tetrahydroisoquinoline

詳細情報

• CRID: 1390001204177669120
• NII論文ID: 130005131597
• NII書誌ID: AA00602100
• DOI: 10.1248/cpb.c15-00803
• ISSN: 13475223
• ISSN: 00092363
• NDL書誌ID: 027133448
• PubMed: 26936050
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I027133448
• Web Site: https://www.jstage.jst.go.jp/article/cpb/64/3/64_c15-00803/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016310933
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可