1-(3-nitrophenyl)-5-methyltetrazole | 40746-64-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(3-nitrophenyl)-5-methyltetrazole
• 英文别名: 5-methyl-1-(3-nitrophenyl)tetrazole；5-methyl-1-(3-nitro-phenyl)-1H-tetrazole；5-Methyl-1-(3-nitro-phenyl)-1H-tetrazol；5-methyl-1-(3-nitrophenyl)-1H-tetrazole；1-(m-Nitrophenyl)-5-methyltetrazol；1-m-Nitrophenyl-5-methyltetrazol
• CAS: 40746-64-3
• 化学式: C₈H₇N₅O₂
• 分子量: 205.176
• InChiKey: KOJZORORFNJKDA-UHFFFAOYSA-N

物化性质

• 熔点：
  148-150 °C
• 沸点：
  400.9±47.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  89.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(3-nitrophenyl)-5-methyltetrazole 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 phenyl 3-(5-methyltetrazol-1-yl)phenylcarbamate
  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：

  间硝基苯甲酰氯 在 sodium azide 、 trifluoromethanesulfonic acid anhydride 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 2.0h， 生成 1-(3-nitrophenyl)-5-methyltetrazole
  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

• A facile and convenient synthesis of substituted tetrazole derivatives from ketones or α,β-unsaturated ketones
  作者：Abdel-Aziz S. El-Ahl、Saad S. Elmorsy、Hanan Soliman、Fathy A. Amer

  DOI：10.1016/0040-4039(95)01513-h

  日期：1995.10

  Triazidochlorosilane (SiCl4 - NaN3 in situ) is a new and efficient reagent for the direct conversion of ketones or α,β-unsaturated ketones to the corresponding tetrazole derivatives in nearly quantitative yield.

  三叠氮氯硅烷（SiCl 4 -NaN 3原位反应）是一种新的有效试剂，可将酮或α，β-不饱和酮直接转化为相应的四唑衍生物，且定量接近收率。
• Kinetics and mechanism of 1-phenyl-5-methyltetrazole nitration in HNO3–H2SO4 system
  作者：V. A. Ostrovskii、A. S. Enin、L. N. Boiko、R. E. Trifonov、E. A. Popova、Yu. N. Pavlyukova、V. Yu. Dolmatov

  DOI：10.1134/s107042801611021x

  日期：2016.11

  At nitration of 1-phenyl-5-methyltetrazole with nitric acid in aqueous solutions of sulfuric acid of 84–96% concentration a mixture forms of 1-(4-nitrophenyl)- and 1-(3-nitrophenyl)-5-methyltetrazoles in a ratio 60: 40. According to kinetic data, the tetrazole ring in the substrate is present in a protonated form. The protonation constants of 1-(4-carboxyphenyl)-5-methyltetrazole at the tetrazole ring

  在浓度为84-96％的硫酸水溶液中用硝酸硝化1-苯基-5-甲基四唑时，会形成1-（4-硝基苯基）-和1-（3-硝基苯基）-5-甲基四唑的混合物形式比率为60∶40。根据动力学数据，底物中的四唑环以质子化形式存在。测定四唑环上的1-（4-羧基苯基）-5-甲基四唑的质子化常数和羧基。计算出质子化的四唑环的哈米特电子常数。
• Modulators of Chemokine Receptor Activity
  申请人：Weigand Klaus

  公开号：US20080306067A1

  公开（公告）日：2008-12-11

  A compound of formula (I), wherein substituents are as given above, useful in the treatment of a disease mediated by the action of CCR3, in particular inflammatory or obstructive airway diseases.

  公式为（I）的化合物，其取代基如上所述，在治疗由CCR3作用介导的疾病中有用，特别是炎症或阻塞性气道疾病。
• Substituted Phenyltetrazoles. Alkoxynitrophenyl-Tetrazoles and Alkoxyaminophenyltetrazoles
  作者：Du-Yung Wu、Robert M. Herbst

  DOI：10.1021/jo50009a006

  日期：1952.9
• WO2007/48771
  申请人：——

  公开号：——

  公开（公告）日：——