4-((S)-3-amino-3-((S)-5,6-difluoro-2,3-dihydro-1H-inden-1-yl)propanoyl)-8-(trifluoromethyl)-4,5-dihydro-1H-benzo[e][1,4]diazepin-2(3H)-one

• 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: 4-((S)-3-amino-3-((S)-5,6-difluoro-2,3-dihydro-1H-inden-1-yl)propanoyl)-8-(trifluoromethyl)-4,5-dihydro-1H-benzo[e][1,4]diazepin-2(3H)-one
• 英文别名: 4-[(3S)-3-amino-3-[(1S)-5,6-difluoro-2,3-dihydro-1H-inden-1-yl]propanoyl]-8-(trifluoromethyl)-3,5-dihydro-1H-1,4-benzodiazepin-2-one
• 化学式: C₂₂H₂₀F₅N₃O₂
• 分子量: 453.412
• InChiKey: CUEWKJJLIOZALC-KSSFIOAISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  75.4
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-硝基-4-(三氟甲基)溴苄 在 palladium 10% on activated carbon 、 氢气 、 铁粉 、 碳酸氢钠 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.11h， 生成 4-((S)-3-amino-3-((S)-5,6-difluoro-2,3-dihydro-1H-inden-1-yl)propanoyl)-8-(trifluoromethyl)-4,5-dihydro-1H-benzo[e][1,4]diazepin-2(3H)-one
  参考文献：
  名称：

  Design, Synthesis, and Pharmacological Evaluation of Fused β-Homophenylalanine Derivatives as Potent DPP-4 Inhibitors

  摘要：

  Dipeptidyl peptidase-4 (DPP-4) inhibitors are accepted as a favorable class of agents for the treatment of type 2 diabetes. Herein, a series of fused beta-homophenylalanine derivatives as novel DPP-4 inhibitors were designed, synthesized, and evaluated for their inhibitory activities against DPP-4. Most of them displayed excellent DPP-4 inhibitory activities and good selectivity. Among them, 9aa, 18a, and 18m also showed good efficacy in an oral glucose tolerance test (OGTT) in ICR mice. Moreover, when dosed 8 h prior to glucose challenge, 18m showed significantly greater potency than sitagliptin. It thus provides potential candidates for the further development into potent drugs targeting DPP-4.

  DOI：

  10.1021/acsmedchemlett.5b00074