2-(6-Bromohexyl)-4-chloro-5-[4-(furan-2-carbonyl)piperazin-1-yl]pyridazin-3-one | 351896-52-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-(6-Bromohexyl)-4-chloro-5-[4-(furan-2-carbonyl)piperazin-1-yl]pyridazin-3-one
• CAS: 351896-52-1
• 化学式: C₁₉H₂₄BrClN₄O₃
• 分子量: 471.782
• InChiKey: YWDWKQNGAXTIGU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  69.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2-氯苯基)哌嗪 、 2-(6-Bromohexyl)-4-chloro-5-[4-(furan-2-carbonyl)piperazin-1-yl]pyridazin-3-one 在 sodium carbonate 作用下， 以 异戊醇 为溶剂， 以35%的产率得到4-Chloro-2-[6-[4-(2-chlorophenyl)piperazin-1-yl]hexyl]-5-[4-(furan-2-carbonyl)piperazin-1-yl]pyridazin-3-one
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Pharmacophore Generation of New Pyridazinone Derivatives with Affinity toward α₁- and α₂-Adrenoceptors

  摘要：

  A series of new pyridazin-3(2H)-one derivatives (3 and 4) were evaluated for their in vitro affinity toward both alpha (1)- and alpha (2)-adrenoceptors by radioligand receptor binding assays. All target compounds showed good affinities for the al-adrenoceptor, with K-i values in the low nanomolar range. The polymethylene chain constituting the spacer between the furoylpiperazinyl pyridazinone and the arylpiperazine moiety was shown to influence the affinity and selectivity of these compounds. Particularly, a gradual increase in affinity was observed by lengthening the polymethylene chain up to a maximum of seven carbon atoms. In addition, compound 3k, characterized by a very interesting alpha (1)-AR affinity (1.9 nM), was also shown to be a highly selective alpha (1)-AR antagonist, the affinity ratio for alpha (2)- and alpha (1)-adrenoceptors being 274. To gain insight into the structural features required for al antagonist activity, the pyridazinone derivatives were submitted to a pharmacophore generation procedure using the program Catalyst. The resulting pharmacophore model showed high correlation and predictive power. It also rationalized the relationships between structural properties and biological data of, and external to, the pyridazinone class.

  DOI：

  10.1021/jm010821u
• 作为产物：
  描述：

  1-(2-糠酰)哌嗪 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 26.0h， 生成 2-(6-Bromohexyl)-4-chloro-5-[4-(furan-2-carbonyl)piperazin-1-yl]pyridazin-3-one
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Pharmacophore Generation of New Pyridazinone Derivatives with Affinity toward α₁- and α₂-Adrenoceptors

  摘要：

  A series of new pyridazin-3(2H)-one derivatives (3 and 4) were evaluated for their in vitro affinity toward both alpha (1)- and alpha (2)-adrenoceptors by radioligand receptor binding assays. All target compounds showed good affinities for the al-adrenoceptor, with K-i values in the low nanomolar range. The polymethylene chain constituting the spacer between the furoylpiperazinyl pyridazinone and the arylpiperazine moiety was shown to influence the affinity and selectivity of these compounds. Particularly, a gradual increase in affinity was observed by lengthening the polymethylene chain up to a maximum of seven carbon atoms. In addition, compound 3k, characterized by a very interesting alpha (1)-AR affinity (1.9 nM), was also shown to be a highly selective alpha (1)-AR antagonist, the affinity ratio for alpha (2)- and alpha (1)-adrenoceptors being 274. To gain insight into the structural features required for al antagonist activity, the pyridazinone derivatives were submitted to a pharmacophore generation procedure using the program Catalyst. The resulting pharmacophore model showed high correlation and predictive power. It also rationalized the relationships between structural properties and biological data of, and external to, the pyridazinone class.

  DOI：

  10.1021/jm010821u

文献信息

• Synthesis, Biological Evaluation, and Pharmacophore Generation of New Pyridazinone Derivatives with Affinity toward α₁- and α₂-Adrenoceptors
  作者：Roberta Barbaro、Laura Betti、Maurizio Botta、Federico Corelli、Gino Giannaccini、Laura Maccari、Fabrizio Manetti、Giovannella Strappaghetti、Stefano Corsano

  DOI：10.1021/jm010821u

  日期：2001.6.1

  A series of new pyridazin-3(2H)-one derivatives (3 and 4) were evaluated for their in vitro affinity toward both alpha (1)- and alpha (2)-adrenoceptors by radioligand receptor binding assays. All target compounds showed good affinities for the al-adrenoceptor, with K-i values in the low nanomolar range. The polymethylene chain constituting the spacer between the furoylpiperazinyl pyridazinone and the arylpiperazine moiety was shown to influence the affinity and selectivity of these compounds. Particularly, a gradual increase in affinity was observed by lengthening the polymethylene chain up to a maximum of seven carbon atoms. In addition, compound 3k, characterized by a very interesting alpha (1)-AR affinity (1.9 nM), was also shown to be a highly selective alpha (1)-AR antagonist, the affinity ratio for alpha (2)- and alpha (1)-adrenoceptors being 274. To gain insight into the structural features required for al antagonist activity, the pyridazinone derivatives were submitted to a pharmacophore generation procedure using the program Catalyst. The resulting pharmacophore model showed high correlation and predictive power. It also rationalized the relationships between structural properties and biological data of, and external to, the pyridazinone class.