Ditert-butyl 2-[(1-benzyl-6-oxopyridazin-4-yl)methylidene]propanedioate | 1001620-43-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: Ditert-butyl 2-[(1-benzyl-6-oxopyridazin-4-yl)methylidene]propanedioate
• CAS: 1001620-43-4
• 化学式: C₂₃H₂₈N₂O₅
• 分子量: 412.486
• InChiKey: BKVLBYVXBLFIPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  85.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Ditert-butyl 2-[(1-benzyl-6-oxopyridazin-4-yl)methylidene]propanedioate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 以49%的产率得到2-[(1-Benzyl-6-oxopyridazin-4-yl)methylidene]propanedioic acid
  参考文献：
  名称：

  Design, Synthesis, and Structure–Activity Relationships of a Novel Series of 5-Alkylidenepyridazin-3(2H)-ones with a Non-cAMP-Based Antiplatelet Activity

  摘要：

  5-Alkylidenepyridazin-3-ones with four points of diversity (R-2, R-6, X, Y) have been synthesized and evaluated as platelet aggregation inhibitors. Several derivatives eliciting antiplatelet activity in the low micromolar range (e.g., 14e, 14k, 14p, 14v, IC50 congruent to 1 mu M) were identified. Structure-activity relationships studies on these compounds revealed the key molecular determinants of this new family of antiplatelet agents: (a) two ester groups in the alkoxy moieties; (b) lipophilic substituents at the N2 position of the pyridazin-3-one. The preliminary results of a pharmacological study aimed at determining the mechanism of action of a set of representative compounds revealed that, unlike other pyridazinones, the documented antiplatelet effect is not a consequence of a PDE-III inhibitory activity.

  DOI：

  10.1021/jm061401d
• 作为产物：
  描述：

  1-苄基-6-氧代-1,6-二氢哒嗪-4-甲醛 、 丙二酸二叔丁酯 在 silica-supported aluminum chloride 作用下， 以 乙醇 为溶剂， 以68%的产率得到Ditert-butyl 2-[(1-benzyl-6-oxopyridazin-4-yl)methylidene]propanedioate
  参考文献：
  名称：

  Silica-Supported Aluminum Chloride-Assisted Solution Phase Synthesis of Pyridazinone-Based Antiplatelet Agents

  摘要：

  A solution phase protocol that enabled the synthesis of three diverse libraries of pyridazin-3-ones incorporating alpha,beta-unsaturated moieties at position S of the heterocyclic core has been developed using silica-supported aluminum trichloride as a heterogeneous and reusable catalyst. This robust procedure has facilitated the hit to lead process for these series of compounds and allowed the identification of new potent derivatives that elicit antiplatelet activity in the low micromolar range.

  DOI：

  10.1021/co100017h

文献信息

• Design, Synthesis, and Structure–Activity Relationships of a Novel Series of 5-Alkylidenepyridazin-3(2<i>H</i>)-ones with a Non-cAMP-Based Antiplatelet Activity
  作者：Alberto Coelho、Enrique Raviña、Nuria Fraiz、Matilde Yáñez、Reyes Laguna、Ernesto Cano、Eddy Sotelo

  DOI：10.1021/jm061401d

  日期：2007.12.27

  5-Alkylidenepyridazin-3-ones with four points of diversity (R-2, R-6, X, Y) have been synthesized and evaluated as platelet aggregation inhibitors. Several derivatives eliciting antiplatelet activity in the low micromolar range (e.g., 14e, 14k, 14p, 14v, IC50 congruent to 1 mu M) were identified. Structure-activity relationships studies on these compounds revealed the key molecular determinants of this new family of antiplatelet agents: (a) two ester groups in the alkoxy moieties; (b) lipophilic substituents at the N2 position of the pyridazin-3-one. The preliminary results of a pharmacological study aimed at determining the mechanism of action of a set of representative compounds revealed that, unlike other pyridazinones, the documented antiplatelet effect is not a consequence of a PDE-III inhibitory activity.
• Silica-Supported Aluminum Chloride-Assisted Solution Phase Synthesis of Pyridazinone-Based Antiplatelet Agents
  作者：Abdelaziz El Maatougui、Jhonny Azuaje、Eddy Sotelo、Olga Caamaño、Alberto Coelho

  DOI：10.1021/co100017h

  日期：2011.1.10

  A solution phase protocol that enabled the synthesis of three diverse libraries of pyridazin-3-ones incorporating alpha,beta-unsaturated moieties at position S of the heterocyclic core has been developed using silica-supported aluminum trichloride as a heterogeneous and reusable catalyst. This robust procedure has facilitated the hit to lead process for these series of compounds and allowed the identification of new potent derivatives that elicit antiplatelet activity in the low micromolar range.