5-benzoyl-4-(4-hydroxy-3-methoxyphenyl)-6-phenyl-3,4-dihydropyrimidin-2(1H)-one | 359450-91-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 5-benzoyl-4-(4-hydroxy-3-methoxyphenyl)-6-phenyl-3,4-dihydropyrimidin-2(1H)-one
• 英文别名: 5-benzoyl-4-(4-hydroxy-3-methoxyphenyl)-6-phenyl-3,4-dihydro-1H-pyrimidin-2-one
• CAS: 359450-91-2
• 化学式: C₂₄H₂₀N₂O₄
• 分子量: 400.434
• InChiKey: NSFHKCWSUNHUMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  香草醛 、 二苯甲酰基甲烷 、 尿素 在 tin(II) chloride dihdyrate 作用下， 以 乙腈 为溶剂， 生成 5-benzoyl-4-(4-hydroxy-3-methoxyphenyl)-6-phenyl-3,4-dihydropyrimidin-2(1H)-one
  参考文献：
  名称：

  Structure based virtual screening-driven identification of monastrol as a potent urease inhibitor

  摘要：

  Virtual screening uses computer based methods to discover new ligands on the basis of biological structures. Among all virtual screening methods structure based docking has received considerable attention. In an attempt to identify new ligands as urease inhibitors, structure-based virtual screening (SBVS) of an in-house database of 10,000 organic compounds was carried out. The X-ray crystallographic structure of Bacillus pasteurii (BP) in complex with acetohydroxamic acid (PDB Code 4UBP) was used as a protein structure. As a starting point, similar to 10,000 compounds of our in-house database were analyzed to check redundancy and the compounds found repeated were removed from the database. Finally 6993 compounds were docked into the active site of BP urease using GOLD and MOE-Dock software. A remarkable feature of this study was the identification of monastrol, a well-known KSP inhibitor already in clinical trials, as a novel urease inhibitor. The hits identified were further evaluated by molecular docking and on examination of the affinity predictions, twenty-seven analogs of monastrol were synthesized by a multicomponent Biginelli reaction followed by their in vitro screening as urease inhibitors. Finally twelve compounds were identified as new urease inhibitors. The excellent in vitro activity suggested that these compounds may serve as viable lead compounds for the treatment of urease related problems. (c) 2013 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.jmgm.2013.04.006

文献信息

• In vitro and in silico exploration of IL-2 inhibition by small drug-like molecules
  作者：Saima Kalsoom、Umer Rashid、Awais Shaukat、Omer Mohamed Abdalla、Khalida Hussain、Waqasuddin Khan、Samina Nazir、Mohammad Ahmad Mesaik、Zaheer-ul-Haq、Farzana Latif Ansari

  DOI：10.1007/s00044-013-0564-x

  日期：2013.12

  Interleukin-2 (IL-2) is an immunoregulatory cytokine produced by T lymphocytes in response to antigen. It is a potent growth and differentiation factor for several cell-types and is structurally related to the four-helix bundle family of cytokines. Here, we report IL-2 inhibitory potential and computational studies on different series of chalcones, benzothiazepines, semicarbazones, and dihydropyrimidines. These compounds were synthesized in wet lab and were then tested for their potency as IL-2 inhibitors through in vitro T cell proliferation, IL-2 cytokine production as well as their effect on oxidative burst. Compounds that showed significant suppressive activity were further evaluated for their cytotoxicity on normal two cell lines. Most of the chalcones were found to have a powerful inhibitory effect on T-lymphocytes proliferation and cytokine production. Among the aza heterocycles benzothiazepines, benzoxazepines, and benzodiazepinones were found to be the strongest IL-2 inhibitors. Molecular docking and MD simulation studies were carried out to correlate experimental and theoretical results whereby a good correlation was observed which indicated that computational studies could provide an alternate tool for the identification and designing of more potent IL-2 inhibitors.
• Structure based virtual screening-driven identification of monastrol as a potent urease inhibitor
  作者：Umer Rashid、Iram Batool、Abdul Wadood、Ajmal Khan、Zaheer ul-Haq、Muhammad Iqbal Chaudhary、Farzana Latif Ansari

  DOI：10.1016/j.jmgm.2013.04.006

  日期：2013.6

  Virtual screening uses computer based methods to discover new ligands on the basis of biological structures. Among all virtual screening methods structure based docking has received considerable attention. In an attempt to identify new ligands as urease inhibitors, structure-based virtual screening (SBVS) of an in-house database of 10,000 organic compounds was carried out. The X-ray crystallographic structure of Bacillus pasteurii (BP) in complex with acetohydroxamic acid (PDB Code 4UBP) was used as a protein structure. As a starting point, similar to 10,000 compounds of our in-house database were analyzed to check redundancy and the compounds found repeated were removed from the database. Finally 6993 compounds were docked into the active site of BP urease using GOLD and MOE-Dock software. A remarkable feature of this study was the identification of monastrol, a well-known KSP inhibitor already in clinical trials, as a novel urease inhibitor. The hits identified were further evaluated by molecular docking and on examination of the affinity predictions, twenty-seven analogs of monastrol were synthesized by a multicomponent Biginelli reaction followed by their in vitro screening as urease inhibitors. Finally twelve compounds were identified as new urease inhibitors. The excellent in vitro activity suggested that these compounds may serve as viable lead compounds for the treatment of urease related problems. (c) 2013 Elsevier Inc. All rights reserved.