{1-[3'-chloro-3-fluoro-2'-(2-methyl-2H-tetrazol-5-yl)-biphenyl-4-yl]-ethyl}-carbamic acid tert-butyl ester | 1048962-75-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: {1-[3'-chloro-3-fluoro-2'-(2-methyl-2H-tetrazol-5-yl)-biphenyl-4-yl]-ethyl}-carbamic acid tert-butyl ester
• CAS: 1048962-75-9
• 化学式: C₂₁H₂₃ClFN₅O₂
• 分子量: 431.897
• InChiKey: LDNKFQOPGAFKGW-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.92
• 重原子数：
  30.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  81.93
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  {1-[3'-chloro-3-fluoro-2'-(2-methyl-2H-tetrazol-5-yl)-biphenyl-4-yl]-ethyl}-carbamic acid tert-butyl ester 在 盐酸 、 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 1.0h， 生成 N-{(1R)-1-[3'-chloro-3-fluoro-2'-(2-methyl-2H-tetrazol-5-yl)-1,1'-biphenyl-4-yl]ethyl}-1-[(trifluoroacetyl)amino]cyclopropanecarboxamide
  参考文献：
  名称：

  Development of Orally Bioavailable and CNS Penetrant Biphenylaminocyclopropane Carboxamide Bradykinin B₁ Receptor Antagonists

  摘要：

  A series of biphenylaminocyclopropane carboxamide based bradykinin B-1 receptor antagonists has been developed that possesses good pharmacokinetic properties and is CNS penetrant. Discovery that the replacement of the trifluoropropionamide in the lead structure with polyhaloacetamides, particularly a trifluoroacetamide, significantly reduced P-glycoprotein mediated efflux for the series proved essential. One of these novel bradykinin B-1 antagonists (13b) also exhibited suitable pharmacokinetic properties and efficient ex vivo receptor occupancy for further development as a novel approach for the treatment of pain and inflammation.

  DOI：

  10.1021/jm061094b
• 作为产物：
  描述：

  N-[(1E)-(4-bromo-2-fluorophenyl)methylidene]-2-methylpropane-2-sulfinamide 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 palladium diacetate 盐酸 、 potassium acetate 、 potassium carbonate 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 8.0h， 生成 {1-[3'-chloro-3-fluoro-2'-(2-methyl-2H-tetrazol-5-yl)-biphenyl-4-yl]-ethyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Development of Orally Bioavailable and CNS Penetrant Biphenylaminocyclopropane Carboxamide Bradykinin B₁ Receptor Antagonists

  摘要：

  A series of biphenylaminocyclopropane carboxamide based bradykinin B-1 receptor antagonists has been developed that possesses good pharmacokinetic properties and is CNS penetrant. Discovery that the replacement of the trifluoropropionamide in the lead structure with polyhaloacetamides, particularly a trifluoroacetamide, significantly reduced P-glycoprotein mediated efflux for the series proved essential. One of these novel bradykinin B-1 antagonists (13b) also exhibited suitable pharmacokinetic properties and efficient ex vivo receptor occupancy for further development as a novel approach for the treatment of pain and inflammation.

  DOI：

  10.1021/jm061094b