tert-butyl 2-(+)-trans-((4-(4-fluorobenzyl)piperidin-1-yl)methyl)cyclohexylcarbamate | 383430-24-8

• 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: tert-butyl 2-(+)-trans-((4-(4-fluorobenzyl)piperidin-1-yl)methyl)cyclohexylcarbamate
• CAS: 383430-24-8
• 化学式: C₂₇H₃₅FN₂O₂
• 分子量: 438.586
• InChiKey: XBJFSQRJHCLGRP-AZGAKELHSA-N

物化性质

• 沸点：
  571.2±33.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.57
• 重原子数：
  32.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  41.57
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-(+)-trans-((4-(4-fluorobenzyl)piperidin-1-yl)methyl)cyclohexylcarbamate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 生成 (1R,2S)-2-[[4-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexan-1-amine
  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
• 作为产物：
  描述：

  反式-2-羟甲基-1-环己胺 盐酸盐 在 草酰氯 、 三乙酰氧基硼氢化钠 、 sodium carbonate 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 tert-butyl 2-(+)-trans-((4-(4-fluorobenzyl)piperidin-1-yl)methyl)cyclohexylcarbamate
  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