(2S,3aS,7aS)-1-((R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-N-cyclopropyloctahydro-1H-indole-2-carboxamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (2S,3aS,7aS)-1-((R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-N-cyclopropyloctahydro-1H-indole-2-carboxamide
• 英文别名: H-bAla(3R-Bn(2,4,5-triF))-Oic-NHcPr；(2S,3aS,7aS)-1-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-N-cyclopropyl-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxamide
• 化学式: C₂₂H₂₈F₃N₃O₂
• 分子量: 423.478
• InChiKey: BDDXQUQHGVSCTR-HJWMAQEXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  75.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  叔丁氧羰基-L-八氢化吲哚-2-羧酸 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 (2S,3aS,7aS)-1-((R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-N-cyclopropyloctahydro-1H-indole-2-carboxamide
  参考文献：
  名称：

  ( R )-3-Amino-1-((3a S ,7a S )-octahydro-1 H -indol-1-yl)-4-(2,4,5-trifluorophenyl)butan-1-one derivatives as potent inhibitors of dipeptidyl peptidase-4: Design, synthesis, biological evaluation, and molecular modeling

  摘要：

  A series of (R)-3-amino-1-((3aS,7aS)-octahydro-1H-indol-1-yl)-4-(2,4,5-trifluorophenyl)butan-1-one derivatives was designed, synthesized, and evaluated as novel inhibitors of dipeptidyl peptidase-4 (DPP-4) for the treatment of type 2 diabetes. Most of the synthesized compounds demonstrated good inhibition activities against DPP-4. Among these, compounds 3e, 4c, 4l, and 4n exhibited prominent inhibition activities against DPP-4, with IC(50)s of 0.07, 0.07, 0.14, and 0.17 mu M, respectively. The possible binding modes of compounds 3e and 4n with dipeptidyl peptidase-4 were also explored by molecular docking simulation. These potent DPP-4 inhibitors were optimized for the absorption, distribution, metabolism, and excretion (ADME) properties, and compound 4n displayed an attractive pharmacokinetic profile (F = 96.3%, t(1/2) = 10.5 h). (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.09.051

文献信息

• ( R )-3-Amino-1-((3a S ,7a S )-octahydro-1 H -indol-1-yl)-4-(2,4,5-trifluorophenyl)butan-1-one derivatives as potent inhibitors of dipeptidyl peptidase-4: Design, synthesis, biological evaluation, and molecular modeling
  作者：Sinan Wang、Mingbo Su、Jiang Wang、Zeng Li、Lei Zhang、Xun Ji、Jingya Li、Jia Li、Hong Liu

  DOI：10.1016/j.bmc.2014.09.051

  日期：2014.12

  A series of (R)-3-amino-1-((3aS,7aS)-octahydro-1H-indol-1-yl)-4-(2,4,5-trifluorophenyl)butan-1-one derivatives was designed, synthesized, and evaluated as novel inhibitors of dipeptidyl peptidase-4 (DPP-4) for the treatment of type 2 diabetes. Most of the synthesized compounds demonstrated good inhibition activities against DPP-4. Among these, compounds 3e, 4c, 4l, and 4n exhibited prominent inhibition activities against DPP-4, with IC(50)s of 0.07, 0.07, 0.14, and 0.17 mu M, respectively. The possible binding modes of compounds 3e and 4n with dipeptidyl peptidase-4 were also explored by molecular docking simulation. These potent DPP-4 inhibitors were optimized for the absorption, distribution, metabolism, and excretion (ADME) properties, and compound 4n displayed an attractive pharmacokinetic profile (F = 96.3%, t(1/2) = 10.5 h). (C) 2014 Elsevier Ltd. All rights reserved.