6-bromo-N-(2-(4-morpholino)ethyl)-1-phthalazinamine | 1071932-13-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-bromo-N-(2-(4-morpholino)ethyl)-1-phthalazinamine
• 英文别名: 1-Phthalazinamine, 6-bromo-N-[2-(4-morpholinyl)ethyl]-；6-bromo-N-(2-morpholin-4-ylethyl)phthalazin-1-amine
• CAS: 1071932-13-2
• 化学式: C₁₄H₁₇BrN₄O
• 分子量: 337.219
• InChiKey: XECZTYPGDWMPRZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  50.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolanyl)benzamide 、 6-bromo-N-(2-(4-morpholino)ethyl)-1-phthalazinamine 在 四(三苯基膦)钯 、 水 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 为溶剂， 反应 1.0h， 以71%的产率得到N-cyclopropyl-4-methyl-3-(1-((2-(4-morpholino)ethyl)amino)-6-phthalazinyl)benzamide
  参考文献：
  名称：

  Discovery of Highly Selective and Potent p38 Inhibitors Based on a Phthalazine Scaffold

  摘要：

  Investigations into the structure-activity relationships (SAR) of a series of phthalazine-based inhibitors of p38 are described. These efforts originated from quinazoline 1 and through rational design led to the development of a series of orally bioavailable, potent, and selective inhibitors. Kinase selectivity was achieved by exploiting a collection of interactions with p38alpha including close contact to Ala157, occupation of the hydrophobic gatekeeper pocket, and a residue flip with Gly110. Substitutions on the phthalazine influenced the pharmacokinetic properties, of which compound 16 displayed the most desirable profile. Oral dosing (0.03 mg/kg) of 16 in rats 1 h prior to LPS challenge gave a >50% decrease in TNFalpha production.

  DOI：

  10.1021/jm8005417
• 作为产物：
  描述：

  N-(2-氨基乙基)吗啉 、 6-溴-1-氯-二氮杂萘 以 异丙醇 为溶剂， 反应 0.08h， 以77%的产率得到6-bromo-N-(2-(4-morpholino)ethyl)-1-phthalazinamine
  参考文献：
  名称：

  Discovery of Highly Selective and Potent p38 Inhibitors Based on a Phthalazine Scaffold

  摘要：

  Investigations into the structure-activity relationships (SAR) of a series of phthalazine-based inhibitors of p38 are described. These efforts originated from quinazoline 1 and through rational design led to the development of a series of orally bioavailable, potent, and selective inhibitors. Kinase selectivity was achieved by exploiting a collection of interactions with p38alpha including close contact to Ala157, occupation of the hydrophobic gatekeeper pocket, and a residue flip with Gly110. Substitutions on the phthalazine influenced the pharmacokinetic properties, of which compound 16 displayed the most desirable profile. Oral dosing (0.03 mg/kg) of 16 in rats 1 h prior to LPS challenge gave a >50% decrease in TNFalpha production.

  DOI：

  10.1021/jm8005417