1-(2-(1′-neopentylspiro[indoline-3,4′-piperidine]-1-yl)-phenyl)-3-(4-(trifluoromethoxy)phenyl)urea

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-(2-(1′-neopentylspiro[indoline-3,4′-piperidine]-1-yl)-phenyl)-3-(4-(trifluoromethoxy)phenyl)urea
• 英文别名: Urea, N-[2-[1'-(2,2-dimethylpropyl)-1,2-dihydrospiro[3H-indole-3,4'-piperidin]-1-yl]phenyl]-N'-[4-(trifluoromethoxy)phenyl]-；1-[2-[1'-(2,2-dimethylpropyl)spiro[2H-indole-3,4'-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea
• 化学式: C₃₁H₃₅F₃N₄O₂
• 分子量: 552.64
• InChiKey: FDCUCZZKNTVJSB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  40
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  56.8
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  螺[吲哚啉-3,4’-哌啶]-1’-羧酸苄酯 在 palladium 10% on activated carbon 、 氢气 、 氯化铵 、 溶剂黄146 、 锌 、 原甲酸三甲酯 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 、 二氯甲烷 为溶剂， 反应 26.5h， 生成 1-(2-(1′-neopentylspiro[indoline-3,4′-piperidine]-1-yl)-phenyl)-3-(4-(trifluoromethoxy)phenyl)urea
  参考文献：
  名称：

  Conformationally Constrained ortho-Anilino Diaryl Ureas: Discovery of 1-(2-(1′-Neopentylspiro[indoline-3,4′-piperidine]-1-yl)phenyl)-3-(4-(trifluoromethoxy)phenyl)urea, a Potent, Selective, and Bioavailable P2Y₁ Antagonist

  摘要：

  Preclinical antithrombotic efficacy and bleeding models have demonstrated that P2Y(1) antagonists are efficacious as antiplatelet agents and may offer a safety advantage over P2Y(12) antagonists in terms of reduced bleeding liabilities. In this article, we describe the structural modification of the tert-butyl phenoxy portion of lead compound 1 and the subsequent discovery of a novel series of conformationally constrained ortho-anilino diaryl ureas. In particular, spiropiperidine indoline-substituted diaryl ureas are described as potent, orally bioavailable small-molecule P2Y(1) antagonists with improved activity in functional assays and improved oral bioavailability in rats. Homology modeling and rat PK/PD studies on benchmark compound 31 will also be presented. Compound 31 was our first P2Y(1) antagonist to demonstrate a robust oral antithrombotic effect with mild bleeding liability in the rat thrombosis and hemostasis models.

  DOI：

  10.1021/jm4013906