N-cyclopropyl-4-methyl-3-(4-(1-methylethoxy)-7-isoquinolinyl)benzamide | 1071932-14-3

• 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: N-cyclopropyl-4-methyl-3-(4-(1-methylethoxy)-7-isoquinolinyl)benzamide
• 英文别名: N-cyclopropyl-4-methyl-3-(4-propan-2-yloxyisoquinolin-7-yl)benzamide
• CAS: 1071932-14-3
• 化学式: C₂₃H₂₄N₂O₂
• 分子量: 360.456
• InChiKey: DKHCMNUPWHVUKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  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

文献信息

• MEDICAMENT FOR TREATMENT OF LIVER CANCER
  申请人：Zender Lars

  公开号：US20150079154A1

  公开（公告）日：2015-03-19

  The invention provides a pharmaceutical composition comprising Sorafenib in combination with an inhibitor of a specific kinase inhibitor as a medicament for the treatment or prevention of liver cancer.
• Discovery of Highly Selective and Potent p38 Inhibitors Based on a Phthalazine Scaffold
  作者：Brad Herberich、Guo-Qiang Cao、Partha P. Chakrabarti、James R. Falsey、Liping Pettus、Robert M. Rzasa、Anthony B. Reed、Andreas Reichelt、Kelvin Sham、Maya Thaman、Ryan P. Wurz、Shimin Xu、Dawei Zhang、Faye Hsieh、Matthew R. Lee、Rashid Syed、Vivian Li、David Grosfeld、Matthew H. Plant、Bradley Henkle、Lisa Sherman、Scot Middleton、Lu Min Wong、Andrew S. Tasker

  DOI：10.1021/jm8005417

  日期：2008.10.23

  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.