ethyl 6-[(E)-[phenyl(pyrimidin-2-yl)methylidene]amino]oxyhexanoate | 180865-62-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl 6-[(E)-[phenyl(pyrimidin-2-yl)methylidene]amino]oxyhexanoate
• CAS: 180865-62-7
• 化学式: C₁₉H₂₃N₃O₃
• 分子量: 341.41
• InChiKey: STAKFFWMCJWDLC-RELWKKBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  73.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 6-[(E)-[phenyl(pyrimidin-2-yl)methylidene]amino]oxyhexanoate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以81%的产率得到6-[(E)-[phenyl(pyrimidin-2-yl)methylidene]amino]oxyhexanoic acid
  参考文献：
  名称：

  On the Bioisosteric Potential of Diazines:  Diazine Analogues of the Combined Thromboxane A₂ Receptor Antagonist and Synthetase Inhibitor Ridogrel

  摘要：

  In this SAR study the bioisosteric potential of diazines in the field of combined antithrombotic thromboxane A(2) synthetase inhibitors and receptor antagonists was investigated. In this context, two series of (E)- and (Z)-omega-[[(aryldiazinylmethylene)amino]oxy]alkanoic acids were synthesized of which pentanoic acid derivatives with a 2-pyrazinyl, 4-pyridazinyl, or 6-pyrimidinyl group were found to exhibit this dual activity, while 4-pyrimidinyl as well as 3-pyridazinyl analogues showed only receptor antagonistic activity and 2-pyrimidinyl congeners were inactive. In the series of diazine analogues of Ridogrel (1), replacement of the 3-pyridyl group by a 2-pyrazinyl, 4-pyridazinyl, or 5-pyrimidinyl moiety led to compounds that inhibit thromboxane A(2) synthetase in gel-filtered human platelets comparable to 1 (IC50 Of 0.006, 0.016, and 0.039 mu M, respectively, versus 0.007 mu M) Radioligand-binding studies with [H-3]SQ 29,548 in washed human platelets revealed that these diazine analogues block the thromboxane Az receptor with an IC50 of 11, 6.0, and 1.5 mu M, respectively. This compares well with the IC50 = 1.7 mu M of 1. Finally, testing of inhibition of collagen-induced platelet aggregation in human platelet-rich plasma with 2-pyrazinyl, 4-pyridazinyl, or 5-pyrimidinyl congeners of Ridogrel indicated that these heteroaromatic moieties may serve as bioisosteric substitutes of a 3-pyridyl group in dual-acting antiplatelet agents.

  DOI：

  10.1021/jm960341g
• 作为产物：
  描述：

  6-溴己酸乙酯 在 盐酸 、 sodium acetate 、 sodium carbonate 、 一水合肼 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 5.84h， 生成 ethyl 6-[(E)-[phenyl(pyrimidin-2-yl)methylidene]amino]oxyhexanoate
  参考文献：
  名称：

  On the Bioisosteric Potential of Diazines:  Diazine Analogues of the Combined Thromboxane A₂ Receptor Antagonist and Synthetase Inhibitor Ridogrel

  摘要：

  In this SAR study the bioisosteric potential of diazines in the field of combined antithrombotic thromboxane A(2) synthetase inhibitors and receptor antagonists was investigated. In this context, two series of (E)- and (Z)-omega-[[(aryldiazinylmethylene)amino]oxy]alkanoic acids were synthesized of which pentanoic acid derivatives with a 2-pyrazinyl, 4-pyridazinyl, or 6-pyrimidinyl group were found to exhibit this dual activity, while 4-pyrimidinyl as well as 3-pyridazinyl analogues showed only receptor antagonistic activity and 2-pyrimidinyl congeners were inactive. In the series of diazine analogues of Ridogrel (1), replacement of the 3-pyridyl group by a 2-pyrazinyl, 4-pyridazinyl, or 5-pyrimidinyl moiety led to compounds that inhibit thromboxane A(2) synthetase in gel-filtered human platelets comparable to 1 (IC50 Of 0.006, 0.016, and 0.039 mu M, respectively, versus 0.007 mu M) Radioligand-binding studies with [H-3]SQ 29,548 in washed human platelets revealed that these diazine analogues block the thromboxane Az receptor with an IC50 of 11, 6.0, and 1.5 mu M, respectively. This compares well with the IC50 = 1.7 mu M of 1. Finally, testing of inhibition of collagen-induced platelet aggregation in human platelet-rich plasma with 2-pyrazinyl, 4-pyridazinyl, or 5-pyrimidinyl congeners of Ridogrel indicated that these heteroaromatic moieties may serve as bioisosteric substitutes of a 3-pyridyl group in dual-acting antiplatelet agents.

  DOI：

  10.1021/jm960341g

文献信息

• On the Bioisosteric Potential of Diazines:  Diazine Analogues of the Combined Thromboxane A₂ Receptor Antagonist and Synthetase Inhibitor Ridogrel
  作者：Gottfried Heinisch、Wolfgang Holzer、Friedbert Kunz、Thierry Langer、Peter Lukavsky、Christoph Pechlaner、Hans Weissenberger

  DOI：10.1021/jm960341g

  日期：1996.1.1

  In this SAR study the bioisosteric potential of diazines in the field of combined antithrombotic thromboxane A(2) synthetase inhibitors and receptor antagonists was investigated. In this context, two series of (E)- and (Z)-omega-[[(aryldiazinylmethylene)amino]oxy]alkanoic acids were synthesized of which pentanoic acid derivatives with a 2-pyrazinyl, 4-pyridazinyl, or 6-pyrimidinyl group were found to exhibit this dual activity, while 4-pyrimidinyl as well as 3-pyridazinyl analogues showed only receptor antagonistic activity and 2-pyrimidinyl congeners were inactive. In the series of diazine analogues of Ridogrel (1), replacement of the 3-pyridyl group by a 2-pyrazinyl, 4-pyridazinyl, or 5-pyrimidinyl moiety led to compounds that inhibit thromboxane A(2) synthetase in gel-filtered human platelets comparable to 1 (IC50 Of 0.006, 0.016, and 0.039 mu M, respectively, versus 0.007 mu M) Radioligand-binding studies with [H-3]SQ 29,548 in washed human platelets revealed that these diazine analogues block the thromboxane Az receptor with an IC50 of 11, 6.0, and 1.5 mu M, respectively. This compares well with the IC50 = 1.7 mu M of 1. Finally, testing of inhibition of collagen-induced platelet aggregation in human platelet-rich plasma with 2-pyrazinyl, 4-pyridazinyl, or 5-pyrimidinyl congeners of Ridogrel indicated that these heteroaromatic moieties may serve as bioisosteric substitutes of a 3-pyridyl group in dual-acting antiplatelet agents.