Carbamic acid,(2,3-dihydro-1h-indol-5-yl)-,phenyl ester | 865538-84-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: Carbamic acid,(2,3-dihydro-1h-indol-5-yl)-,phenyl ester
• 英文别名: phenyl N-(2,3-dihydro-1H-indol-5-yl)carbamate
• CAS: 865538-84-7
• 化学式: C₁₅H₁₄N₂O₂
• 分子量: 254.288
• InChiKey: UFJUDWVPCGWBDK-UHFFFAOYSA-N

物化性质

• 沸点：
  404.9±45.0 °C(Predicted)
• 密度：
  1.274±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  50.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Carbamic acid,(2,3-dihydro-1h-indol-5-yl)-,phenyl ester 、 (1R,2S)-2-(((S)-3-(4-fluorobenzyl)piperidin-1-yl)methyl)cyclohexylamine 以 氯仿 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 1-((1R,2S)-2-(((S)-3-(4-fluorobenzyl)piperidin-1-yl)methyl)cyclohexyl)-3-(indolin-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
• 作为产物：
  描述：

  C₂₀H₂₂N₂O₄ 在 三氟乙酸 、 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 反应 2.25h， 生成 Carbamic acid,(2,3-dihydro-1h-indol-5-yl)-,phenyl ester
  参考文献：
  名称：

  Oxazolidinone antibacterial agents having a thiocarbonyl functionality

  摘要：

  本发明提供了式1化合物： 或药物可接受的盐，其中A，G和R1如权利要求中所定义，它们是抗菌剂。

  公开号：

  US06342513B1

文献信息

• Oxazolidinone antibacterial agents having a thiocarbonyl functionality
  申请人：Pharmacia and Upjohn Company

  公开号：US06342513B1

  公开（公告）日：2002-01-29

  The present invention provides compounds of Formula 1: or pharmaceutical acceptable salts thereof wherein A, G and R1 are as defined in the claims which are antibacterial agents.

  本发明提供了式1化合物： 或药物可接受的盐，其中A，G和R1如权利要求中所定义，它们是抗菌剂。
• Discovery of CC Chemokine Receptor-3 (CCR3) Antagonists with Picomolar Potency
  作者：George V. De Lucca、Ui Tae Kim、Brian J. Vargo、John V. Duncia、Joseph B. Santella、Daniel S. Gardner、Changsheng Zheng、Ann Liauw、Zhang Wang、George Emmett、Dean A. Wacker、Patricia K. Welch、Maryanne Covington、Nicole C. Stowell、Eric A. Wadman、Anuk M. Das、Paul Davies、Swamy Yeleswaram、Danielle M. Graden、Kimberly A. Solomon、Robert C. Newton、George L. Trainor、Carl P. Decicco、Soo. S. Ko

  DOI：10.1021/jm049530m

  日期：2005.3.1

  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.