1-甲基-6-氧代-3-苯基-1,6-二氢哒嗪-4-甲醛 | 1001620-74-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 1-甲基-6-氧代-3-苯基-1,6-二氢哒嗪-4-甲醛
• 英文名称: 1-methyl-6-oxo-3-phenyl-1,6-dihydropyridazine-4-carbaldehyde
• 英文别名: 1-methyl-6-oxo-3-phenylpyridazine-4-carbaldehyde
• CAS: 1001620-74-1
• 化学式: C₁₂H₁₀N₂O₂
• 分子量: 214.224
• InChiKey: CCSOJHBLKVTEPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  49.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-甲基-6-氧代-3-苯基-1,6-二氢哒嗪-4-甲醛 、 丙二酸二乙酯 在 silica-supported aluminum chloride 作用下， 以 乙醇 为溶剂， 以78%的产率得到Diethyl 2-[(1-methyl-6-oxo-3-phenylpyridazin-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
• 作为产物：
  描述：

  5-Ethenyl-2-methyl-6-phenylpyridazin-3-one 在 氧气 、 臭氧 、 二甲基硫 作用下， 以 二氯甲烷 为溶剂， 反应 0.58h， 以83%的产率得到1-甲基-6-氧代-3-苯基-1,6-二氢哒嗪-4-甲醛
  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

文献信息

• Efficient Consecutive Alkylation-Knoevenagel Functionalisations in Formyl Aza-Heterocycles Using Supported Organic Bases
  作者：Artur Silva、Alberto Coelho、Abdelaziz El-Maatougui、Enrique Raviña、José Cavaleiro

  DOI：10.1055/s-2006-951559

  日期：——

  An efficient solution-phase parallel procedure to perform the structural diversification of some formyl aza-heterocycles employing supported organic bases (PS-BEMP, PS-TBD or Si-TBD) is described. The library synthesis is based on a consecutive alkylation-Knoevenagel functionalisation that employs alkyl halides, Michael acceptors, and malonic acid derivatives as diversity elements.

  本文描述了一种高效的溶液相并行过程，利用负载型有机碱（PS-BEMP、PS-TBD或Si-TBD）对某些醛基氮杂环进行结构多样化的方法。该库合成基于连续的烷基化-Knoevenagel功能化反应，采用烷基卤、迈克尔受体和丙二酸衍生物作为多样性元素。
• Supported TBD-Assisted Solution Phase Diversification of Formyl-Aza-Heterocycles Through Alkylation-Knoevenagel One Pot Sequences
  作者：Abdelaziz El Maatougui、Abel Crespo、Artur M.S. Silva、Alberto Coelho

  DOI：10.2174/138620711796367229

  日期：2011.8.1

  An efficient solution-phase parallel procedure to perform the structural diversification of some formyl-nitrogen heterocycles (A) using the reusable TBD supported base is described. The library synthesis is based in a consecutive Alkylation-Knoevenagel functionalisation that uses alkyl halides (B), Michael acceptors (C) and activated methylene compounds (D) as diversity elements.

  报道了一种高效的原位并行方法，用于实现某些甲酰氮杂环（A）的结构多样化，该方法利用可重复使用的TBD负载碱。库合成基于连续的烷基化-Knoevenagel官能化，采用烷基卤化物（B）、Michael受体（C）和活化甲基酮化合物（D）作为多样性元素。
• 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.