4-<4-(1-acetyl-4-piperidinyl)phenyl>-4-oxobutanoic acid | 112069-10-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-<4-(1-acetyl-4-piperidinyl)phenyl>-4-oxobutanoic acid
• 英文别名: 4-[4-(1-acetylpiperidin-4-yl)phenyl]-4-oxobutanoic acid
• CAS: 112069-10-0
• 化学式: C₁₇H₂₁NO₄
• 分子量: 303.358
• InChiKey: FIMKUKORYHFWRP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.46
• 重原子数：
  22.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  74.68
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  4-<4-(1-acetyl-4-piperidinyl)phenyl>-4-oxobutanoic acid 在 盐酸 作用下， 以86%的产率得到4-<4-(4-piperidinyl)phenyl>-4-oxobutanoic acid hydrochloride
  参考文献：
  名称：

  Imidazole-pyridine bioisosterism: comparison of the inotropic activities of pyridine- and imidazole-substituted 6-phenyldihydropyridazinone cardiotonics

  摘要：

  We previously reported the structure-activity relationships (SAR), molecular structure, pharmacology, and molecular pharmacology of indolidan (LY195115), a potent and long-acting dihydropyridazinone cardiotonic. Our 6-phenyldihydropyridazinone SAR studies revealed the critical nature of the substituent at the para position of the phenyl ring. An acetamido substituent provided potent cardiotonic activity and we hypothesized that this may relate to the ability of the acetamide carbonyl to function as a hydrogen-bond acceptor. To further address this question, we prepared 15 (4,5-dihydro-6-[4-(3-pyridinyl)phenyl]-3(2H)-pyridazinone), the 3-pyridyl analogue of imazodan. As is the case with imazodan, this (pyridylphenyl)dihydropyridazinone possesses a nitrogen three atoms removed from the phenyl ring, but the molecular framework through which it is attached to the phenyldihydropyridazinone moiety is altered. After iv administration to pentobarbital-anesthetized dogs, inotropic ED50 values of 15, imazodan, and the parent compound, 4,5-dihydro-6-phenyl-3(2H)-pyridazinone, were 19.4, 50.1, and 6330 micrograms/kg, respectively. Thus, 15 is over 2-fold more potent than imazodan and 326-fold more potent than the parent, unsubstituted compound. These data, as well as data obtained with other congeners, are consistent with the hypothesis that a suitably oriented hydrogen-bond-acceptor site contributes to the high degree of inotropic potency observed with these dihydropyridazinone cardiotonics.

  DOI：

  10.1021/jm00397a033
• 作为产物：
  描述：

  4-苯基哌啶 在 三氯化铝 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 4-<4-(1-acetyl-4-piperidinyl)phenyl>-4-oxobutanoic acid
  参考文献：
  名称：

  Imidazole-pyridine bioisosterism: comparison of the inotropic activities of pyridine- and imidazole-substituted 6-phenyldihydropyridazinone cardiotonics

  摘要：

  We previously reported the structure-activity relationships (SAR), molecular structure, pharmacology, and molecular pharmacology of indolidan (LY195115), a potent and long-acting dihydropyridazinone cardiotonic. Our 6-phenyldihydropyridazinone SAR studies revealed the critical nature of the substituent at the para position of the phenyl ring. An acetamido substituent provided potent cardiotonic activity and we hypothesized that this may relate to the ability of the acetamide carbonyl to function as a hydrogen-bond acceptor. To further address this question, we prepared 15 (4,5-dihydro-6-[4-(3-pyridinyl)phenyl]-3(2H)-pyridazinone), the 3-pyridyl analogue of imazodan. As is the case with imazodan, this (pyridylphenyl)dihydropyridazinone possesses a nitrogen three atoms removed from the phenyl ring, but the molecular framework through which it is attached to the phenyldihydropyridazinone moiety is altered. After iv administration to pentobarbital-anesthetized dogs, inotropic ED50 values of 15, imazodan, and the parent compound, 4,5-dihydro-6-phenyl-3(2H)-pyridazinone, were 19.4, 50.1, and 6330 micrograms/kg, respectively. Thus, 15 is over 2-fold more potent than imazodan and 326-fold more potent than the parent, unsubstituted compound. These data, as well as data obtained with other congeners, are consistent with the hypothesis that a suitably oriented hydrogen-bond-acceptor site contributes to the high degree of inotropic potency observed with these dihydropyridazinone cardiotonics.

  DOI：

  10.1021/jm00397a033

文献信息

• ROBERTSON, DAVID W.;KRUSHINSKI, JOSEPH H.;POLLOCK, G. DON;HAYES, J. SCOTT, J. MED. CHEM., 31,(1988) N 2, 461-465
  作者：ROBERTSON, DAVID W.、KRUSHINSKI, JOSEPH H.、POLLOCK, G. DON、HAYES, J. SCOTT

  DOI：——

  日期：——