1-(3-chlorophenyl)-8,8-dimethyl-4-(4-fluorophenyl)-3-phenyl-7,9-dioxa-1,2-diaza-spiro[4.5]dec-2-ene-6,10-dione | 1246461-41-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 1-(3-chlorophenyl)-8,8-dimethyl-4-(4-fluorophenyl)-3-phenyl-7,9-dioxa-1,2-diaza-spiro[4.5]dec-2-ene-6,10-dione
• 英文别名: 1-(3-Chlorophenyl)-4-(4-fluorophenyl)-8,8-dimethyl-3-phenyl-7,9-dioxa-1,2-diazaspiro[4.5]dec-2-ene-6,10-dione
• CAS: 1246461-41-5
• 化学式: C₂₆H₂₀ClFN₂O₄
• 分子量: 478.907
• InChiKey: OXUOLUQJRYNCSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  34
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  68.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-(4-fluorobenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 、 N'-(3-chlorophenyl)benzohydrazonoyl chloride 在 三乙胺 作用下， 以 苯 为溶剂， 反应 15.0h， 以67%的产率得到1-(3-chlorophenyl)-8,8-dimethyl-4-(4-fluorophenyl)-3-phenyl-7,9-dioxa-1,2-diaza-spiro[4.5]dec-2-ene-6,10-dione
  参考文献：
  名称：

  Regioselective synthesis and molecular modeling study of vasorelaxant active 7,9-dioxa-1,2-diaza-spiro[4.5]dec-2-ene-6,10-diones

  摘要：

  Nitrilimines (PhC-:N+:NR') generated in situ from hydrazonoyl chlorides 2a,b reacted regioselectively with 5-arylidene-2,2-dimethyl[1,3]dioxane-4,6-diones 1a-f to afford 1.3,4-triaryl-8,8-dimethyl-7,9-dioxa-1,2-diaza-spiro[4.5]dec-2-ene-6,10-diones 3a-1. In vitro vasodilation activity screening of the synthesized compounds using isolated thoracic aortic rings of male Wister rats pre-contracted with norepinephrine hydrochloride revealed considerable vasodilation activity: compounds 3f and 3j had IC50 (concentration necessary for 50% reduction of maximal norepinephrine hydrochloride induced contracture) of 0.325, 0.321 mM, respectively. Molecular modeling, including fitting to a 3D-pharma-cophore model using Discovery studio 2.1 programs and their docking into optimized alpha(1)-AR homology models as alpha(1)-AR antagonist showed high-docking score and fit values. The experimental in vitro vasodilation activity of compounds 3a-1 was consistent with the molecular modeling. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.06.018

文献信息

• Regioselective synthesis and molecular modeling study of vasorelaxant active 7,9-dioxa-1,2-diaza-spiro[4.5]dec-2-ene-6,10-diones
  作者：Adel S. Girgis、Nasser S.M. Ismail、Hanaa Farag、Wafaa I. El-Eraky、Dalia O. Saleh、Srinivasa R. Tala、Alan R. Katritzky

  DOI：10.1016/j.ejmech.2010.06.018

  日期：2010.9

  Nitrilimines (PhC-:N+:NR') generated in situ from hydrazonoyl chlorides 2a,b reacted regioselectively with 5-arylidene-2,2-dimethyl[1,3]dioxane-4,6-diones 1a-f to afford 1.3,4-triaryl-8,8-dimethyl-7,9-dioxa-1,2-diaza-spiro[4.5]dec-2-ene-6,10-diones 3a-1. In vitro vasodilation activity screening of the synthesized compounds using isolated thoracic aortic rings of male Wister rats pre-contracted with norepinephrine hydrochloride revealed considerable vasodilation activity: compounds 3f and 3j had IC50 (concentration necessary for 50% reduction of maximal norepinephrine hydrochloride induced contracture) of 0.325, 0.321 mM, respectively. Molecular modeling, including fitting to a 3D-pharma-cophore model using Discovery studio 2.1 programs and their docking into optimized alpha(1)-AR homology models as alpha(1)-AR antagonist showed high-docking score and fit values. The experimental in vitro vasodilation activity of compounds 3a-1 was consistent with the molecular modeling. (C) 2010 Elsevier Masson SAS. All rights reserved.