4,5-dihydro-6-[4-(3-pyridinyl)phenyl]-3(2H)-pyridazinone | 104431-85-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4,5-dihydro-6-[4-(3-pyridinyl)phenyl]-3(2H)-pyridazinone
• 英文别名: 6-[4-(Pyridin-3-yl)phenyl]-4,5-dihydropyridazin-3(2H)-one；3-(4-pyridin-3-ylphenyl)-4,5-dihydro-1H-pyridazin-6-one
• CAS: 104431-85-8
• 化学式: C₁₅H₁₃N₃O
• 分子量: 251.288
• InChiKey: FOSONUIQKLCHNZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-苯基吡啶 在 三氯化铝 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 12.0h， 生成 4,5-dihydro-6-[4-(3-pyridinyl)phenyl]-3(2H)-pyridazinone
  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

• Pyridylphenylpyridazinone inotropic agents
  申请人：ELI LILLY AND COMPANY

  公开号：EP0178875A1

  公开（公告）日：1986-04-23

  57 This invention provides compounds of the formula wherein R1, R2, R3, R4, R5, and R6 are independently hydrogen or C1-C4 alkyl, or R6 and one of R4 and R5 taken together form a bond; and acid addition salts thereof which are useful as inotropic agents.

  57 本发明提供了式中 R1、R2、R3、R4、R5 和 R6 独立地为氢或 C1-C4 烷基，或 R6 与 R4 和 R5 中的一个共同形成键的化合物；及其可用作肌力剂的酸加成盐。
• 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：——
• ——
  作者：ROBERTSON D. W.

  DOI：——

  日期：——
• US4631279A
  申请人：——

  公开号：US4631279A

  公开（公告）日：1986-12-23