N-(2-fluoro-4-methoxyphenyl)-2-(trifluoroacetyl)-2,3-dihydro-1H-isoindole-5-sulfonamide | 1400652-86-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2-fluoro-4-methoxyphenyl)-2-(trifluoroacetyl)-2,3-dihydro-1H-isoindole-5-sulfonamide
• 英文别名: N-(2-fluoro-4-methoxyphenyl)-2-(2,2,2-trifluoroacetyl)-1,3-dihydroisoindole-5-sulfonamide
• CAS: 1400652-86-9
• 化学式: C₁₇H₁₄F₄N₂O₄S
• 分子量: 418.369
• InChiKey: RMXDTYHTEWIIIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  84.1
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-(2-fluoro-4-methoxyphenyl)-2-(trifluoroacetyl)-2,3-dihydro-1H-isoindole-5-sulfonamide 在 水 、 三乙胺 、 potassium hydroxide 作用下， 以 乙醇 、 氯仿 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成 N-(4-tert-butylphenyl)-5-[(2-fluoro-4-methoxyphenyl)sulfamoyl]-1,3-dihydro-2H-isoindole-2-carboxamide
  参考文献：
  名称：

  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

  摘要：

  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. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.06.065
• 作为产物：
  描述：

  1-(1,3-dihydro-2H-isoindol-2-yl)-2,2,2-trifluoroethanone 在 吡啶 、 氯磺酸 、 4-二甲氨基吡啶 作用下， 以 氯仿 为溶剂， 反应 15.0h， 生成 N-(2-fluoro-4-methoxyphenyl)-2-(trifluoroacetyl)-2,3-dihydro-1H-isoindole-5-sulfonamide
  参考文献：
  名称：

  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

  摘要：

  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. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.06.065

文献信息

• 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
• 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
  作者：Tsuyoshi Busujima、Hiroaki Tanaka、Yoshihisa Shirasaki、Eiji Munetomo、Masako Saito、Kiyokazu Kitano、Toshiya Minagawa、Koji Yoshida、Naoto Osaki、Nagaaki Sato

  DOI：10.1016/j.bmc.2015.06.065

  日期：2015.9

  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. (C) 2015 Elsevier Ltd. All rights reserved.