N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-2-(trifluoroacetyl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide | 1400654-03-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-2-(trifluoroacetyl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide
• 英文别名: N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-2-(2,2,2-trifluoroacetyl)-3,4-dihydro-1H-isoquinoline-6-sulfonamide
• CAS: 1400654-03-6
• 化学式: C₂₅H₂₈F₄N₂O₃S
• 分子量: 512.569
• InChiKey: LKEWMBKYAMOHPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-2-(trifluoroacetyl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide 在 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 19.08h， 生成 2-[2-(4-tert-Butylphenyl)ethyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide
  参考文献：
  名称：

  An Efficient and Convenient Synthesis of Acyl CoA: Monoacylglycerol Acyltransferase 2 Inhibitor, 2-[2-(4-tert-Butylphenyl)ethyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide

  摘要：

  An efficient and convenient synthesis of MGAT2 inhibitor, 2-[2-(4-tert-butylphenyl)ethyl]-N44-(3-cyclopentylpropy1)-2-fluorophenyl]-1,2,3, 4-tetrahydroisoquinoline-6-sulfonamide (1), is reported. The optimized route consists of an effective chlorosulfonylation and debromination, resulting in an increase in the total yield from 6.8% to 45%, compared with our previous method. This synthetic approach enabled the synthesis of 1 to be scaled-up to a multi-gram scale.

  DOI：

  10.3987/com-15-13387
• 作为产物：
  描述：

  1-(3,4-二氢-2(1H)-异喹啉基)-2,2,2-三氟乙烷酮 在 吡啶 、 氯磺酸 、 4-二甲氨基吡啶 作用下， 以 氯仿 为溶剂， 反应 19.0h， 生成 N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-2-(trifluoroacetyl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide
  参考文献：
  名称：

  An Efficient and Convenient Synthesis of Acyl CoA: Monoacylglycerol Acyltransferase 2 Inhibitor, 2-[2-(4-tert-Butylphenyl)ethyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide

  摘要：

  An efficient and convenient synthesis of MGAT2 inhibitor, 2-[2-(4-tert-butylphenyl)ethyl]-N44-(3-cyclopentylpropy1)-2-fluorophenyl]-1,2,3, 4-tetrahydroisoquinoline-6-sulfonamide (1), is reported. The optimized route consists of an effective chlorosulfonylation and debromination, resulting in an increase in the total yield from 6.8% to 45%, compared with our previous method. This synthetic approach enabled the synthesis of 1 to be scaled-up to a multi-gram scale.

  DOI：

  10.3987/com-15-13387

文献信息

• 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
  作者：Tsuyoshi Busujima、Hiroaki Tanaka、Kanako Iwakiri、Yoshihisa Shirasaki、Eiji Munetomo、Masako Saito、Aiko Masuko、Kiyokazu Kitano、Fusayo Io、Koji Kato、Shunsuke Kamigaso、Akiko Nozoe、Nagaaki Sato

  DOI：10.1248/cpb.c15-00803

  日期：——

  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.

  我们之前报道了2-[2-(4-叔丁基苯基)乙基]-N-(4-氟苯基)-1,2,3,4-四氢异喹啉-6-磺酰胺2，这是一种口服可用的单酰甘油酰基转移酶2（MGAT2）抑制剂，在小鼠口服脂质耐受测试中以100 mg/kg的剂量表现出体内疗效。对化合物2进行进一步优化以提高内在效力，最终确定了化合物11。化合物11对人类MGAT2酶的IC50值比2低超过50倍。在口服脂质耐受测试中以3 mg/kg的剂量口服给药11导致三酸甘油脂合成显著抑制。
• NITROGEN-CONTAINING CONDENSED HETEROCYCLIC COMPOUND
  申请人：Taisho Pharmaceutical Co., Ltd.

  公开号：EP2687507B1

  公开（公告）日：2016-03-09
• US9035059B2
  申请人：——

  公开号：US9035059B2

  公开（公告）日：2015-05-19
• An Efficient and Convenient Synthesis of Acyl CoA: Monoacylglycerol Acyltransferase 2 Inhibitor, 2-[2-(4-tert-Butylphenyl)ethyl]-N-[4-(3-cyclopentylpropyl)-2-fluorophenyl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide
  作者：Tsuyoshi Busujima、Hiroaki Tanaka

  DOI：10.3987/com-15-13387

  日期：——

  An efficient and convenient synthesis of MGAT2 inhibitor, 2-[2-(4-tert-butylphenyl)ethyl]-N44-(3-cyclopentylpropy1)-2-fluorophenyl]-1,2,3, 4-tetrahydroisoquinoline-6-sulfonamide (1), is reported. The optimized route consists of an effective chlorosulfonylation and debromination, resulting in an increase in the total yield from 6.8% to 45%, compared with our previous method. This synthetic approach enabled the synthesis of 1 to be scaled-up to a multi-gram scale.