1-(2-(1-Neopentyl-2',3'-dihydro-1'H-spiro[piperidine-4,4'-quinoline]-1'-yl)phenyl)-3-(4-(trifluoromethoxy)phenyl)urea

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-(2-(1-Neopentyl-2',3'-dihydro-1'H-spiro[piperidine-4,4'-quinoline]-1'-yl)phenyl)-3-(4-(trifluoromethoxy)phenyl)urea
• 英文别名: 1-[2-[1'-(2,2-Dimethylpropyl)spiro[2,3-dihydroquinoline-4,4'-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea；1-[2-[1'-(2,2-dimethylpropyl)spiro[2,3-dihydroquinoline-4,4'-piperidine]-1-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea
• 化学式: C₃₂H₃₇F₃N₄O₂
• 分子量: 566.667
• InChiKey: INFBWUAALLMHAI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  41
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 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：

  1'-(2,2,2-trifluoroacetyl)spiro[indene-1,4'-piperidin]-3(2H)-one 在 tris-(dibenzylideneacetone)dipalladium(0) 、 lithium aluminium tetrahydride 、 sodium azide 、 硫酸 、 氯化铵 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三乙胺 、 potassium hydroxide 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氯仿 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 140.0h， 生成 1-(2-(1-Neopentyl-2',3'-dihydro-1'H-spiro[piperidine-4,4'-quinoline]-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