1-((1R,2S)-2-(((S)-3-(4-fluorobenzyl)piperidin-1-yl)methyl)cyclohexyl)-3-(3H-benzo[d]imidazol-5-yl)urea

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-((1R,2S)-2-(((S)-3-(4-fluorobenzyl)piperidin-1-yl)methyl)cyclohexyl)-3-(3H-benzo[d]imidazol-5-yl)urea
• 英文别名: 1-(3H-benzimidazol-5-yl)-3-[(1R,2S)-2-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexyl]urea
• 化学式: C₂₇H₃₄FN₅O
• 分子量: 463.598
• InChiKey: ABUUFHZOOKCABN-AWRGLXIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  73
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-苄基-3-哌啶酮盐酸盐 在 palladium on activated charcoal 盐酸 、 正丁基锂 、 D-扁桃酸 、 氢气 、 三乙酰氧基硼氢化钠 、 碳酸氢钠 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 正己烷 、 二氯甲烷 、 氯仿 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， -78.0~20.0 ℃ 、379.21 kPa 条件下， 反应 54.0h， 生成 1-((1R,2S)-2-(((S)-3-(4-fluorobenzyl)piperidin-1-yl)methyl)cyclohexyl)-3-(3H-benzo[d]imidazol-5-yl)urea
  参考文献：
  名称：

  Discovery of CC Chemokine Receptor-3 (CCR3) Antagonists with Picomolar Potency

  摘要：

  Starting with our previously described(20) class of CC chemokine receptor-3 (CCR3) antagonist, we improved the potency by replacing the phenyl linker of 1 with a cyclohexyl linker and by replacing the 4-benzylpiperidine with a 3-benzylpiperidine. The resulting compound, 32, is a potent and selective antagonist of CCR3. SAR studies showed that the 3-acetylphenyl urea of 32 could be replaced with heterocyclic ureas or heterocyclic-substituted phenyl ureas and still maintain the potency (inhibition of eotaxin-induced chemotaxis) of this class of compounds in the low-picomolar range (IC50 = 10-60 pM), representing some of the most potent CCR3 antagonists reported to date. The potency of 32 for mouse CCR3 (chemotaxis IC50 = 41 nM) and its oral bioavailability in mice (20% F) were adequate to assess the efficacy in animal models of allergic airway inflammation. Oral administration of 32 reduced eosinophil recruitment into the lungs in a dose-dependent manner in these animal models. On the basis of its overall potency, selectivity, efficacy, and safety profile, the benzenesulfonate salt of 32, designated DPC168, entered phase 1 clinical trials.

  DOI：

  10.1021/jm049530m