N-(2-ethoxy-4-fluorophenyl)-2-(trifluoroacetyl)-2,3-dihydro-1H-isoindole-5-sulfonamide | 1400652-79-0

• 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-ethoxy-4-fluorophenyl)-2-(trifluoroacetyl)-2,3-dihydro-1H-isoindole-5-sulfonamide
• 英文别名: N-(2-ethoxy-4-fluorophenyl)-2-(2,2,2-trifluoroacetyl)-1,3-dihydroisoindole-5-sulfonamide
• CAS: 1400652-79-0
• 化学式: C₁₈H₁₆F₄N₂O₄S
• 分子量: 432.396
• InChiKey: IPRMTXXYXRQXLD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 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-ethoxy-4-fluorophenyl)-2-(trifluoroacetyl)-2,3-dihydro-1H-isoindole-5-sulfonamide 在 水 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 生成
  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-ethoxy-4-fluorophenyl)-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：EP2687507A1

  公开（公告）日：2014-01-22

  There are provided compounds represented by the following general formula (I) or pharmaceutically acceptable salts of thereof, which have a superior monoacylglycerol acyltransferase 2 inhibitory action: wherein Ring A represents a partially saturated heteroaryl group, an aryl group or a heteroaryl group, RB represents a C4-18 alkyl group, a C3-8 cycloalkyl group, a partially saturated aryl group, an aryl group, or the following formula (II): wherein V represents the formula -CR11R12-, -CO-, -CO-O-, or -CO-NH-, W represents a single bond or a C1-3 alkylene group, and Ring B represents a C3-8 cycloalkyl group, a C3-8 cycloalkenyl group, a partially saturated heteroaryl group, a saturated heterocyclyl group, an aryl group, or a heteroaryl group, Y represents a nitrogen atom or the formula N+(RF), RF represents a C1-4 alkyl group, and m and n, which may be the same or different, each represent an integer of 0 or 1.

  本文提供了由以下通式（I）代表的化合物或其药学上可接受的盐类，它们具有优异的单酰基甘油酰基转移酶 2 抑制作用： 其中 环 A 代表部分饱和杂芳基、芳基或杂芳基，RB 代表 C4-18 烷基、C3-8 环烷基、部分饱和芳基、芳基或下式 (II)： 其中 V 代表式-CR11R12-、-CO-、-CO-O-或-CO-NH-、 W 代表单键或 C1-3 烯基，以及 环 B 代表 C3-8 环烷基、C3-8 环烯基、部分饱和杂芳基、饱和杂环烯基、芳基或杂芳基、 Y 代表氮原子或式 N+(RF)、 RF 代表 C1-4 烷基，以及 m 和 n（可以相同或不同）分别代表 0 或 1 的整数。
• 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.