3-(1-bromo-6-phthalazinyl)-N-cyclopropyl-4-methylbenzamide | 1071932-17-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 3-(1-bromo-6-phthalazinyl)-N-cyclopropyl-4-methylbenzamide
• 英文别名: 3-(4-bromoisoquinolin-7-yl)-N-cyclopropyl-4-methylbenzamide
• CAS: 1071932-17-6
• 化学式: C₂₀H₁₇BrN₂O
• 分子量: 381.272
• InChiKey: UUNOSXUOXDAIDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(1-bromo-6-phthalazinyl)-N-cyclopropyl-4-methylbenzamide 、 异丙醇 在 palladium diacetate 、 caesium carbonate 、 1-naphthyl-di-tert-butylphosphine 作用下， 以 甲苯 为溶剂， 反应 20.0h， 以50 mg的产率得到N-cyclopropyl-4-methyl-3-(4-(1-methylethoxy)-7-isoquinolinyl)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-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolanyl)benzamide 、 4,7-二溴异喹啉 在 四(三苯基膦)钯 、 水 、 sodium carbonate 作用下， 以 乙二醇二甲醚 为溶剂， 反应 16.0h， 以114 mg的产率得到3-(1-bromo-6-phthalazinyl)-N-cyclopropyl-4-methylbenzamide
  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