3-Oxo-2-[1-(2-trifluoromethyl-phenyl)-meth-(Z)-ylidene]-butyric acid 2-(1,1,3-trioxo-1,3-dihydro-1λ6-benzo[d]isothiazol-2-yl)-ethyl ester | 141294-05-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 3-Oxo-2-[1-(2-trifluoromethyl-phenyl)-meth-(Z)-ylidene]-butyric acid 2-(1,1,3-trioxo-1,3-dihydro-1λ6-benzo[d]isothiazol-2-yl)-ethyl ester
• CAS: 141294-05-5
• 化学式: C₂₁H₁₆F₃NO₆S
• 分子量: 467.422
• InChiKey: PTDCKJUKSAJUNT-VBKFSLOCSA-N

物化性质

• 沸点：
  529.5±60.0 °C(Predicted)
• 密度：
  1.465±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.07
• 重原子数：
  32.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  97.82
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (E)-3-Amino-but-2-enoic acid tetrahydro-furan-2-ylmethyl ester 、 3-Oxo-2-[1-(2-trifluoromethyl-phenyl)-meth-(Z)-ylidene]-butyric acid 2-(1,1,3-trioxo-1,3-dihydro-1λ6-benzo[d]isothiazol-2-yl)-ethyl ester 以 乙醇 为溶剂， 反应 20.0h， 以66%的产率得到5-O-(oxolan-2-ylmethyl) 3-O-[2-(1,1,3-trioxo-1,2-benzothiazol-2-yl)ethyl] 2,6-dimethyl-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Synthesis of 3-[(2,3-dihydro-1,1,3-trioxo-1,2-benzisothiazol-2-yl)alkyl] 1,4-dihydropyridine-3,5-dicarboxylate derivatives as calcium channel modulators

  摘要：

  1,4-Dihydropyridine (DHP) derivatives with a 1,2-benzisothiazol-3-one 1,1-dioxide group, linked through an alkylene bridge to the C-3 carboxylate of the DHP ring, with both vasconstricting and vasorelaxant properties were obtained. In blocking Ca2+-evoked contractions of K+-depolarized rabbit aortic strips, compounds 12 and 41 were 10-fold more potent than nifedipine; 27 other compounds were 1-4-fold more potent. Their vascular versus cardiac selectivity was very pronounced; for instance, the selectivity index for compound 41 was 70-fold higher than that of nifedipine. This was also true for the vasoconstricting compound 22, which was as potent as Bay K 8644 in enhancing the Ca2+-evoked contractions of rabbit aorta strips, yet it had poor inotropic activity in rabbit left atria. Oral adminstration of compounds 38, 40, 43, and 53 (20 mg/kg) caused a 35-37% decrease in systolic blood pressure in spontaneously hypertensive rats (SHR); these effects were similar to those of nifedipine. However, iv administration of these compounds to anesthetized SHR caused a decrease in blood pressure which was more pronounced and long-lasting than that of nifedipine. When administered iv at 100-mu-g/kg, the vasoconstricting compound 22 caused a 40% increase in systolic and diastolic blood pressure. Compound 22 exhibited an unusually interesting feature over the other five Ca2+ DHP agonists: it had diester substitutions at the C-3 and C-5 positions of the DHP ring. Overall, compounds processing these properties might be useful in treating clinical cardiovascular conditions in which DHP Ca2+ antagonists or agonists are indicated.

  DOI：

  10.1021/jm00091a008
• 作为产物：
  描述：

  邻三氟甲基苯甲醛 、 2-(1,1,3-trioxo-2,3-dihydro-1,2-benzisothiazol-2-yl)ethyl acetylacetate 在 哌啶 、 溶剂黄146 作用下， 以 异丙醇 为溶剂， 以87%的产率得到3-Oxo-2-[1-(2-trifluoromethyl-phenyl)-meth-(Z)-ylidene]-butyric acid 2-(1,1,3-trioxo-1,3-dihydro-1λ6-benzo[d]isothiazol-2-yl)-ethyl ester
  参考文献：
  名称：

  Synthesis of 3-[(2,3-dihydro-1,1,3-trioxo-1,2-benzisothiazol-2-yl)alkyl] 1,4-dihydropyridine-3,5-dicarboxylate derivatives as calcium channel modulators

  摘要：

  1,4-Dihydropyridine (DHP) derivatives with a 1,2-benzisothiazol-3-one 1,1-dioxide group, linked through an alkylene bridge to the C-3 carboxylate of the DHP ring, with both vasconstricting and vasorelaxant properties were obtained. In blocking Ca2+-evoked contractions of K+-depolarized rabbit aortic strips, compounds 12 and 41 were 10-fold more potent than nifedipine; 27 other compounds were 1-4-fold more potent. Their vascular versus cardiac selectivity was very pronounced; for instance, the selectivity index for compound 41 was 70-fold higher than that of nifedipine. This was also true for the vasoconstricting compound 22, which was as potent as Bay K 8644 in enhancing the Ca2+-evoked contractions of rabbit aorta strips, yet it had poor inotropic activity in rabbit left atria. Oral adminstration of compounds 38, 40, 43, and 53 (20 mg/kg) caused a 35-37% decrease in systolic blood pressure in spontaneously hypertensive rats (SHR); these effects were similar to those of nifedipine. However, iv administration of these compounds to anesthetized SHR caused a decrease in blood pressure which was more pronounced and long-lasting than that of nifedipine. When administered iv at 100-mu-g/kg, the vasoconstricting compound 22 caused a 40% increase in systolic and diastolic blood pressure. Compound 22 exhibited an unusually interesting feature over the other five Ca2+ DHP agonists: it had diester substitutions at the C-3 and C-5 positions of the DHP ring. Overall, compounds processing these properties might be useful in treating clinical cardiovascular conditions in which DHP Ca2+ antagonists or agonists are indicated.

  DOI：

  10.1021/jm00091a008