ethyl 2-(benzyl-{2-[(4-cyanophenoxy)methyl]-2,4-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-6-yl}amino)-2-oxoacetate | 1056737-47-3

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: ethyl 2-(benzyl-{2-[(4-cyanophenoxy)methyl]-2,4-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-6-yl}amino)-2-oxoacetate
• CAS: 1056737-47-3
• 化学式: C₂₉H₂₉N₃O₅
• 分子量: 499.566
• InChiKey: BDISACGLZIGNQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.32
• 重原子数：
  37.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  92.1
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  ethyl 2-(benzyl-{2-[(4-cyanophenoxy)methyl]-2,4-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-6-yl}amino)-2-oxoacetate 在 盐酸 、 ammonium acetate 作用下， 以 乙醇 为溶剂， 反应 24.5h， 以33%的产率得到ethyl 2-(benzyl-{2-[(4-carbamimidoylphenoxy)methyl]-2,4-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-6-yl}amino)-2-oxoacetate
  参考文献：
  名称：

  3,4-Dihydro-2H-1,4-benzoxazine Derivatives Combining Thrombin Inhibitory and Glycoprotein IIb/IIIa Receptor Antagonistic Activity as a Novel Class of Antithrombotic Compounds with Dual Function

  摘要：

  3,4-Dihydro-2H-1,4-benzoxazine derivatives possessing both thrombin inhibitory and glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonistic activities were obtained by combining mimetics of the D-Phe-Pro-Arg pharmacophore of thrombin inhibitors and the Arg-Gly-Asp pharmacophor of GPIIb/IIIa receptor antagonists in the same low molecular weight peptidomimetic compound. Systematic variation of the position of substituents around the 3,4-dihydro-2H-1,4-benzoxazine nucleus, the distance between the carboxylate and amidine moieties, together with additional substituents to fill the thrombin S-2 and S-3 pockets resulted in compounds displaying submicromolar inhibition constants (K-i) for thrombin and submicromolar IC50 for inhibition of binding of fibrinogen to platelet GPIIb/IIIa receptor. Some of these compounds, such as 17a, 17b, 17d, and 17h possessing a well balanced activity at both targets, are a good starting point for further optimization. Incorporation of anticoagulant and platelet antiaggregatory activity in the same molecule constitutes a promising approach toward novel antithrombotic agents.

  DOI：

  10.1021/jm8003448
• 作为产物：
  描述：

  4-[(6-benzylamino-2,4-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl)methoxy]benzonitrile 、 草酰氯单乙酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以98%的产率得到ethyl 2-(benzyl-{2-[(4-cyanophenoxy)methyl]-2,4-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-6-yl}amino)-2-oxoacetate
  参考文献：
  名称：

  3,4-Dihydro-2H-1,4-benzoxazine Derivatives Combining Thrombin Inhibitory and Glycoprotein IIb/IIIa Receptor Antagonistic Activity as a Novel Class of Antithrombotic Compounds with Dual Function

  摘要：

  3,4-Dihydro-2H-1,4-benzoxazine derivatives possessing both thrombin inhibitory and glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonistic activities were obtained by combining mimetics of the D-Phe-Pro-Arg pharmacophore of thrombin inhibitors and the Arg-Gly-Asp pharmacophor of GPIIb/IIIa receptor antagonists in the same low molecular weight peptidomimetic compound. Systematic variation of the position of substituents around the 3,4-dihydro-2H-1,4-benzoxazine nucleus, the distance between the carboxylate and amidine moieties, together with additional substituents to fill the thrombin S-2 and S-3 pockets resulted in compounds displaying submicromolar inhibition constants (K-i) for thrombin and submicromolar IC50 for inhibition of binding of fibrinogen to platelet GPIIb/IIIa receptor. Some of these compounds, such as 17a, 17b, 17d, and 17h possessing a well balanced activity at both targets, are a good starting point for further optimization. Incorporation of anticoagulant and platelet antiaggregatory activity in the same molecule constitutes a promising approach toward novel antithrombotic agents.

  DOI：

  10.1021/jm8003448