N-[4-(1H-pyrazol-4-yl)phenyl]-3,4-dihydro-1H-isoquinoline-2-carboxamide | 1431632-34-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-[4-(1H-pyrazol-4-yl)phenyl]-3,4-dihydro-1H-isoquinoline-2-carboxamide
• CAS: 1431632-34-6
• 化学式: C₁₉H₁₈N₄O
• 分子量: 318.378
• InChiKey: KITGKRAVFNXHDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  61
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-吡唑硼酸频哪醇酯 、 N-(4-bromophenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 生成 N-[4-(1H-pyrazol-4-yl)phenyl]-3,4-dihydro-1H-isoquinoline-2-carboxamide
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Urea Derivatives as Highly Potent and Selective Rho Kinase Inhibitors

  摘要：

  RhoA and its downstream effector ROCK mediate stress fiber formation and cell contraction through their effects on the phosphorylation of myosin light chain (MLC). Inhibition of the RhoA/ROCK pathway has proven to be a promising strategy for several indications such as cardiovascular disease, glaucoma, and inflammatory disease. In 2010, our group reported urea-based ROCK inhibitors as potential antiglaucoma agents. These compounds showed potent IC50 values in enzymatic and cell-based assays and significant intraocular pressure (IOP)-lowering effects in rats (similar to 7 mmHg).(22) To develop more advanced ROCK inhibitors targeting various potential applications (such as myocardial infarction, erectile dysfunction, multiple sclerosis, etc.) in addition to glaucoma, a thorough SAR for this urea-based scaffold was studied. The detailed optimization process, counter-screening, and in vitro and in vivo DMPK studies are discussed. Potent and selective ROCK inhibitors with various in vivo pharmacokinetic properties were discovered.

  DOI：

  10.1021/jm400062r