8-(methoxy)-3-(3'-(trifluoromethyl)phenyl)-5H-indeno[1,2-c]pyridazin-5-one

• 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: 8-(methoxy)-3-(3'-(trifluoromethyl)phenyl)-5H-indeno[1,2-c]pyridazin-5-one
• 英文别名: 6-methoxy-2-[3-(trifluoromethyl)phenyl]-9H-indeno[1,2-c]pyridazin-9-one；3-(3-trifluoromethyl)phenyl-8-methoxy-5H-indeno[1,2-c]pyridazin-5-one；8-methoxy-3-[3-(trifluoromethyl)phenyl]indeno[1,2-c]pyridazin-5-one
• 化学式: C₁₉H₁₁F₃N₂O₂
• 分子量: 356.304
• InChiKey: BWEQEBUJVMCEEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  52.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  间三氟甲基苯乙酮 在 一水合肼 、 溶剂黄146 作用下， 反应 6.0h， 生成 8-(methoxy)-3-(3'-(trifluoromethyl)phenyl)-5H-indeno[1,2-c]pyridazin-5-one
  参考文献：
  名称：

  Synthesis, Structural Reassignment, and Biological Activity of Type B MAO Inhibitors Based on the 5H-Indeno[1,2-c]pyridazin-5-one Core

  摘要：

  The synthesis and enzyme inhibitor properties of reversible type B monoamine oxidase inhibitors are described. These compounds belong to the 5H-indeno[ 1,2-c] pyridazine family and possess a hydrophobic benzyloxy or 4,4,4-trifluorobutoxy side chain which, in contrast to a previous assignment, has been unambiguously located at C( 8) of the heterocyclic moiety. Investigation of the regioisomeric structures establishes that substitution of the 5H-indeno[ 1,2-c] pyridazin-5-one core at C( 7) vs C( 8) dramatically influences the MAO-inhibiting properties of these compounds.

  DOI：

  10.1021/jm051091j

文献信息

• Synthesis and inhibition study of monoamine oxidase, indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase by 3,8-substituted 5H-indeno[1,2-c]pyridazin-5-one derivatives
  作者：J. Reniers、C. Meinguet、L. Moineaux、B. Masereel、S.P. Vincent、R. Frederick、J. Wouters

  DOI：10.1016/j.ejmech.2011.09.042

  日期：2011.12

  Previous studies on 5H-indeno[1,2-c]pyridazin-5-one derivatives as inhibitors of MAO-B revealed that it was possible to increase the MAO-B inhibitory potency of 5H-indeno[1,2-c]pyridazin-5-ones by substituting the central heterocycle in the 3-position or C-8 with lipophilic groups which occupy the substrate cavity or the entrance of the binding site, respectively. Here, four new 5H-indeno[1,2-c]pyridazin-5-one derivatives containing lipophilic groups at both positions were synthesized and their inhibitory potency against human monoamine oxidase A and B were evaluated. Selectivity of these compounds against IDO and TDO, two enzymes sharing substrate similarity with MAO and involved in the serotonergic and kynurenine pathways was also studied. All compounds showed higher activity and selectivity against MAO-B, the most effective one being 3-methyl-8-meta-chlorobenzyloxy-5H-indeno [1,2-c]pyridazin-5-one (9a) which was shown to be a competitive inhibitor with a K-i value of 0.11 mu M. Replacing the methyl group in the 3-position with a meta-CF3-phenyl group (7a, 7b and 7c) abolished the inhibitory potency against MAO-B. Indeed, the substitution of the 5H-indeno[1,2-c]pyridazin-5-one core in the 3-position dramatically influences the MAO-inhibiting properties of these compounds. Molecular docking studies of 9a within MAO-B suggest that the 5H-indeno[1,2-c]pyridazin-5-one scaffold is well stabilized into the substrate cavity with the meta-chlorobenzyloxy side chain extending towards a rather hydrophobic pocket at the entrance cavity. (C) 2011 Elsevier Masson SAS. All rights reserved.
• [EN] PYRIDAZIN-3(2H)-ONE DERIVATIVES WHICH ARE SELECTIVE INHIBITORS OF THE ISOFORM B OF MONOAMINE OXIDASE<br/>[ES] DERIVADOS DE PIRIDAZIN-3(2H)-ONA INHIBIDORES SELECTIVOS DE LA ISOFORMA B DE LA MONOAMINOOXIDASA<br/>[FR] DÉRIVÉS DE PYRIDAZINE-3(2H)-ONE, INHIBITEURS SÉLECTIFS DE L'ISOFORME B DE LA MONOAMINE OXYDASE
  申请人：UNIV VIGO

  公开号：WO2015132427A1

  公开（公告）日：2015-09-11

  Esta invención se refiere a derivados de piridazin-3(2H)-ona de estructura general (I), (II) y (III), que son inhibidores selectivos de la MAO-B, y a su uso para preparar medicamentos destinados a tratar trastornos derivados de la hiperactividad de la MAO-B, en particular trastornos degenerativos del sistema nervioso central (SNC), como la enfermedad de Pakinson (EP), la enfermedad de Alzheimer (EA) y otras demencias. Se trata de derivados de piridazin-3(2H)-ona que presentan fragmentos de ditiocarbamato enlazados a la posición 4, 5 o 6 a través de una cadena alquílica de longitud variable (n=l, 2, 3). Esta invención también se dirige a la preparación de dichos compuestos.
• Synthesis, Structural Reassignment, and Biological Activity of Type B MAO Inhibitors Based on the 5<i>H</i>-Indeno[1,2-<i>c</i>]pyridazin-5-one Core
  作者：Raphaël Frédérick、Willy Dumont、Frédéric Ooms、Lindsey Aschenbach、Cornelis J. Van der Schyf、Neal Castagnoli、Johan Wouters、Alain Krief

  DOI：10.1021/jm051091j

  日期：2006.6.1

  The synthesis and enzyme inhibitor properties of reversible type B monoamine oxidase inhibitors are described. These compounds belong to the 5H-indeno[ 1,2-c] pyridazine family and possess a hydrophobic benzyloxy or 4,4,4-trifluorobutoxy side chain which, in contrast to a previous assignment, has been unambiguously located at C( 8) of the heterocyclic moiety. Investigation of the regioisomeric structures establishes that substitution of the 5H-indeno[ 1,2-c] pyridazin-5-one core at C( 7) vs C( 8) dramatically influences the MAO-inhibiting properties of these compounds.