4-(((7-氯-2-(羟甲基)-3-甲基-4-氧代-3,4-二氢喹唑啉-6-基)甲基)(丙-2 | 1258400-25-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 4-(((7-氯-2-(羟甲基)-3-甲基-4-氧代-3,4-二氢喹唑啉-6-基)甲基)(丙-2
• 英文名称: 4-[{[7-chloro-2-(hydroxymethyl)-3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl]methyl}(prop-2-yn-1-yl)amino]-N-(pyridin-3-ylmethyl)benzamid
• 英文别名: 4-(((7-chloro-2-(hydroxymethyl)-3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)methyl)(prop-2-ynyl)amino)-N-(pyridin-3-ylmethyl)benzamide；4-[[7-chloro-2-(hydroxymethyl)-3-methyl-4-oxoquinazolin-6-yl]methyl-prop-2-ynylamino]-N-(pyridin-3-ylmethyl)benzamide
• CAS: 1258400-25-7
• 化学式: C₂₇H₂₄ClN₅O₃
• 分子量: 501.972
• InChiKey: LYLSVBJJUVIZMD-UHFFFAOYSA-N

物化性质

• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  98.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(((7-氯-2-(羟甲基)-3-甲基-4-氧代-3,4-二氢喹唑啉-6-基)甲基)(丙-2 、 甲基磺酸酐 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Analogues of 4-[(7-Bromo-2-methyl-4-oxo-3H-quinazolin-6-yl)methylprop-2-ynylamino]-N-(3-pyridylmethyl)benzamide (CB-30865) as Potent Inhibitors of Nicotinamide Phosphoribosyltransferase (Nampt)

  摘要：

  We have shown previously that the target of the potent cytatoxic agent 4-[(7-bromo-2-methyl-4-oxo-3H-quinazolin-6-yl)methyl-prop-2-ynylamino]-N-(3-pyridylmethyl)benzamide (CB38065, 1) is nicotinamide phosphoribosyltransferase (Nampt). With its cellular target known we sought to optimize the biochemical and cellular Nampt activity of 1 as well as its cytotoxicity. It was found that a 3-pyridyl-methylamide substituent in the A region was critical to cellular Nampt activity and cytotoxicity, although other aromatic substitution did yield compounds with submicromolar enzymatic inhibition. Small unsaturated groups worked best in the D-region of the molecule, with 3,3-dimethylallyl providing optimal potency. The E region required a quinazolin-4-one or 1,2,3-benzotriazin-4-one group for activity, and many substituents were tolerated at C(2) of the quinazolin-4-one. The best compounds showed subnanomolar inhibition of Nampt and low nanomolar cytotoxicity in cellular assays.

  DOI：

  10.1021/jm101145b
• 作为产物：
  描述：

  (7-氯-3-甲基-4-氧代-6-((丙-2-炔-1-基(4-((吡啶-3-基甲基)氨基甲酰 在 硫酸 作用下， 以 甲醇 为溶剂， 生成 4-(((7-氯-2-(羟甲基)-3-甲基-4-氧代-3,4-二氢喹唑啉-6-基)甲基)(丙-2
  参考文献：
  名称：

  Analogues of 4-[(7-Bromo-2-methyl-4-oxo-3H-quinazolin-6-yl)methylprop-2-ynylamino]-N-(3-pyridylmethyl)benzamide (CB-30865) as Potent Inhibitors of Nicotinamide Phosphoribosyltransferase (Nampt)

  摘要：

  We have shown previously that the target of the potent cytatoxic agent 4-[(7-bromo-2-methyl-4-oxo-3H-quinazolin-6-yl)methyl-prop-2-ynylamino]-N-(3-pyridylmethyl)benzamide (CB38065, 1) is nicotinamide phosphoribosyltransferase (Nampt). With its cellular target known we sought to optimize the biochemical and cellular Nampt activity of 1 as well as its cytotoxicity. It was found that a 3-pyridyl-methylamide substituent in the A region was critical to cellular Nampt activity and cytotoxicity, although other aromatic substitution did yield compounds with submicromolar enzymatic inhibition. Small unsaturated groups worked best in the D-region of the molecule, with 3,3-dimethylallyl providing optimal potency. The E region required a quinazolin-4-one or 1,2,3-benzotriazin-4-one group for activity, and many substituents were tolerated at C(2) of the quinazolin-4-one. The best compounds showed subnanomolar inhibition of Nampt and low nanomolar cytotoxicity in cellular assays.

  DOI：

  10.1021/jm101145b

文献信息

• Analogues of 4-[(7-Bromo-2-methyl-4-oxo-3<i>H</i>-quinazolin-6-yl)methylprop-2-ynylamino]-<i>N</i>-(3-pyridylmethyl)benzamide (CB-30865) as Potent Inhibitors of Nicotinamide Phosphoribosyltransferase (Nampt)
  作者：Jeffrey W. Lockman、Brett R. Murphy、Daniel F. Zigar、Weston R. Judd、Paul M. Slattum、Zhong-Hua Gao、Kirill Ostanin、Jeremy Green、Rena McKinnon、Ryan T. Terry-Lorenzo、Tracey C. Fleischer、J. Jay Boniface、Mark Shenderovich、J. Adam Willardsen

  DOI：10.1021/jm101145b

  日期：2010.12.23

  We have shown previously that the target of the potent cytatoxic agent 4-[(7-bromo-2-methyl-4-oxo-3H-quinazolin-6-yl)methyl-prop-2-ynylamino]-N-(3-pyridylmethyl)benzamide (CB38065, 1) is nicotinamide phosphoribosyltransferase (Nampt). With its cellular target known we sought to optimize the biochemical and cellular Nampt activity of 1 as well as its cytotoxicity. It was found that a 3-pyridyl-methylamide substituent in the A region was critical to cellular Nampt activity and cytotoxicity, although other aromatic substitution did yield compounds with submicromolar enzymatic inhibition. Small unsaturated groups worked best in the D-region of the molecule, with 3,3-dimethylallyl providing optimal potency. The E region required a quinazolin-4-one or 1,2,3-benzotriazin-4-one group for activity, and many substituents were tolerated at C(2) of the quinazolin-4-one. The best compounds showed subnanomolar inhibition of Nampt and low nanomolar cytotoxicity in cellular assays.