3-(bromomethyl)-5H-indeno[1,2-c]pyridazin-5-one | 828265-47-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(bromomethyl)-5H-indeno[1,2-c]pyridazin-5-one
• 英文别名: 5H-Indeno[1,2-c]pyridazin-5-one, 3-(bromomethyl)-；3-(bromomethyl)indeno[1,2-c]pyridazin-5-one
• CAS: 828265-47-0
• 化学式: C₁₂H₇BrN₂O
• 分子量: 275.104
• InChiKey: MKXUAOOZRYSVBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  42.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  potassium phenolate 、 3-(bromomethyl)-5H-indeno[1,2-c]pyridazin-5-one 以 乙醇 为溶剂， 反应 0.5h， 以46%的产率得到3-(phenoxymethyl)-5H-indeno[1,2-c]pyridazin-5-one
  参考文献：
  名称：

  Synthesis and Monoamine Oxidase Inhibitory Activity of New Pyridazine-, Pyrimidine- and 1,2,4-Triazine-Containing Tricyclic Derivatives

  摘要：

  A number of condensed azines, mostly belonging to the families of indeno-fused pyridazines (1), pyrimidines (13), and 12,4-triazines (4, 5), were synthesized and evaluated in vitro as monoamine oxidase (MAO) A and B inhibitors. Most of them showed higher inhibition potency toward MAO-B, the most effective one being 3-(3-nitrophenyl)-9H-indeno[1,2-e] [1,2,4]triazin-9-one (4c), which displayed an IC50 value of 80 nM and proved to be I 0-fold more potent than its [2,1-e] fusion isomer 5. Replacing the 3-phenyl group of the known indeno[12-c]pyridazin-5-one MAO-B inhibitors with a flexible phenoxymethyl group enhanced the inhibitory potency. The inhibition data highlighted the importance of the aza-heterocyclic scaffold in affecting the MAO isoform selectivity. The 3-phenyl derivatives with type 1, 4, and 5 scaffolds were inhibitors of MAO-B with little or no MAO-A effect, whereas 2- or 3-phenyl derivatives of type 2 and 3 pyrimidine-containing fusion isomers inhibited both isoenzymes with a structure-dependent preference toward MAOA.

  DOI：

  10.1021/jm070728r
• 作为产物：
  描述：

  NSC 663887 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 作用下， 以 四氯化碳 为溶剂， 以50%的产率得到3-(bromomethyl)-5H-indeno[1,2-c]pyridazin-5-one
  参考文献：
  名称：

  新型有效和选择性芳香化酶抑制剂的设计，合成和3D QSAR。

  摘要：

  报道了一系列新的芳香酶抑制剂的设计，合成和生物学评估，这些抑制剂带有与芴（A），茚并二嗪（B）或香豆素骨架（C）连接的咪唑或三唑环。与17-α-羟化酶/ 17-20裂解酶相比，正确取代的香豆素衍生物显示出最高的芳香酶抑制能力和选择性。通过比较分子场分析（CoMFA / GOLPE 3D QSAR方法）对芳香化酶抑制数据进行建模，导致了具有良好拟合和预测能力（n = 22，ONC = 3，r（2）= 0.949， s = 0.216，而q（2）= 0.715）。

  DOI：

  10.1021/jm049535j

文献信息

• Design, Synthesis, and 3D QSAR of Novel Potent and Selective Aromatase Inhibitors
  作者：Francesco Leonetti、Angelo Favia、Angela Rao、Rosaria Aliano、Anja Paluszcak、Rolf W. Hartmann、Angelo Carotti

  DOI：10.1021/jm049535j

  日期：2004.12.1

  imidazole or triazole ring linked to a fluorene (A), indenodiazine (B), or coumarin scaffold (C) are reported. Properly substituted coumarin derivatives displayed the highest aromatase inhibitory potency and selectivity over 17-alpha-hydroxylase/17-20 lyase. The modeling of the aromatase inhibition data by Comparative Molecular Field Analysis (CoMFA/GOLPE 3D QSAR approach) led to the development of a PLS

  报道了一系列新的芳香酶抑制剂的设计，合成和生物学评估，这些抑制剂带有与芴（A），茚并二嗪（B）或香豆素骨架（C）连接的咪唑或三唑环。与17-α-羟化酶/ 17-20裂解酶相比，正确取代的香豆素衍生物显示出最高的芳香酶抑制能力和选择性。通过比较分子场分析（CoMFA / GOLPE 3D QSAR方法）对芳香化酶抑制数据进行建模，导致了具有良好拟合和预测能力（n = 22，ONC = 3，r（2）= 0.949， s = 0.216，而q（2）= 0.715）。
• Synthesis and Monoamine Oxidase Inhibitory Activity of New Pyridazine-, Pyrimidine- and 1,2,4-Triazine-Containing Tricyclic Derivatives
  作者：Andrea Carotti、Marco Catto、Francesco Leonetti、Francesco Campagna、Ramón Soto-Otero、Estefanía Méndez-Álvarez、Ulrike Thull、Bernard Testa、Cosimo Altomare

  DOI：10.1021/jm070728r

  日期：2007.11.1

  A number of condensed azines, mostly belonging to the families of indeno-fused pyridazines (1), pyrimidines (13), and 12,4-triazines (4, 5), were synthesized and evaluated in vitro as monoamine oxidase (MAO) A and B inhibitors. Most of them showed higher inhibition potency toward MAO-B, the most effective one being 3-(3-nitrophenyl)-9H-indeno[1,2-e] [1,2,4]triazin-9-one (4c), which displayed an IC50 value of 80 nM and proved to be I 0-fold more potent than its [2,1-e] fusion isomer 5. Replacing the 3-phenyl group of the known indeno[12-c]pyridazin-5-one MAO-B inhibitors with a flexible phenoxymethyl group enhanced the inhibitory potency. The inhibition data highlighted the importance of the aza-heterocyclic scaffold in affecting the MAO isoform selectivity. The 3-phenyl derivatives with type 1, 4, and 5 scaffolds were inhibitors of MAO-B with little or no MAO-A effect, whereas 2- or 3-phenyl derivatives of type 2 and 3 pyrimidine-containing fusion isomers inhibited both isoenzymes with a structure-dependent preference toward MAOA.