[4-(1-methyl-1H-tetrazol-5-yl)-phenyl]-carbamic acid phenyl ester | 382637-69-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: [4-(1-methyl-1H-tetrazol-5-yl)-phenyl]-carbamic acid phenyl ester
• 英文别名: phenyl N-[4-(1-methyltetrazol-5-yl)phenyl]carbamate
• CAS: 382637-69-6
• 化学式: C₁₅H₁₃N₅O₂
• 分子量: 295.301
• InChiKey: OHYDHNHTLMLQDV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  81.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [4-(1-methyl-1H-tetrazol-5-yl)-phenyl]-carbamic acid phenyl ester 、 (1R,2S)-2-(((S)-3-(4-fluorobenzyl)piperidin-1-yl)methyl)cyclohexylamine 以 乙腈 为溶剂， 生成 1-{(1R,2S)-2-[(S)-3-(4-Fluoro-benzyl)-piperidin-1-ylmethyl]-cyclohexyl}-3-[4-(1-methyl-1H-tetrazol-5-yl)-phenyl]-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：

  1-甲基-5-(4-硝基苯基)-1H-四唑 在 palladium on activated charcoal 2,6-二甲基吡啶 、 氢气 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 [4-(1-methyl-1H-tetrazol-5-yl)-phenyl]-carbamic acid phenyl ester
  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

文献信息

• Piperidine amides as modulators of chemo kine receptor activity
  申请人：——

  公开号：US20020156102A1

  公开（公告）日：2002-10-24

  The present application describes modulators of CCR3 of formula (I): 1 or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.

  本申请描述了公式（I）的CCR3调节剂或其药用盐形式，可用于预防哮喘和其他过敏性疾病。
• N-ureidoalkyl-piperidines as modulators of chemokine receptor activity
  申请人：Bristol-Myers Squibb Pharma Co.

  公开号：US06525069B1

  公开（公告）日：2003-02-25

  The present application describes modulators of CCR3 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.

  本申请描述了CCR3的调节剂，其化学式为（I）：或其药用盐形式，可用于预防哮喘和其他过敏性疾病。
• Piperidine amides as modulators of chemokine receptor activity
  申请人：——

  公开号：US20040082790A1

  公开（公告）日：2004-04-29

  The present application describes modulators of CCR3 of formula (I): 1 or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.

  本申请描述了CCR3调节剂的化学式(I):1或其药学上可接受的盐形式，用于预防哮喘和其他过敏性疾病。
• N-UREIDOALKYL-PIPERIDINES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：EP1294690A2

  公开（公告）日：2003-03-26
• PIPERIDINE AMIDES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：EP1296949A2

  公开（公告）日：2003-04-02