methyl 4'-{[({1-[(tert-butoxycarbonyl)amino]cyclopropyl}carbonyl)amino]methyl}-3,3'-difluoro-1,1'-biphenyl-2-carboxylate | 935430-84-5

• 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: methyl 4'-{[({1-[(tert-butoxycarbonyl)amino]cyclopropyl}carbonyl)amino]methyl}-3,3'-difluoro-1,1'-biphenyl-2-carboxylate
• 英文别名: Methyl 2-fluoro-6-[3-fluoro-4-[[[1-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopropanecarbonyl]amino]methyl]phenyl]benzoate
• CAS: 935430-84-5
• 化学式: C₂₄H₂₆F₂N₂O₅
• 分子量: 460.478
• InChiKey: ZIKAZWFXCCDGOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 4'-{[({1-[(tert-butoxycarbonyl)amino]cyclopropyl}carbonyl)amino]methyl}-3,3'-difluoro-1,1'-biphenyl-2-carboxylate 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 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 Methyl 2-[4-[[[1-[(2-chloro-2-fluoroacetyl)amino]cyclopropanecarbonyl]amino]methyl]-3-fluorophenyl]-6-fluorobenzoate
  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：

  methyl 4'-(aminomethyl)-3,3'-difluoro-1,1'-biphenyl-2-carboxylate hydrochloride 、 Boc-1-氨基环丙基甲酸 在 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 为溶剂， 以1.04 g的产率得到methyl 4'-{[({1-[(tert-butoxycarbonyl)amino]cyclopropyl}carbonyl)amino]methyl}-3,3'-difluoro-1,1'-biphenyl-2-carboxylate
  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