4-(4-chloro-2-fluorophenyl)-2-(2-ethoxypyridin-4-yl)-N-(6-fluoro-1H-indazol-5-yl)-6-methyl-1,4-dihydropyrimidine-5-carboxamide | 874119-96-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 4-(4-chloro-2-fluorophenyl)-2-(2-ethoxypyridin-4-yl)-N-(6-fluoro-1H-indazol-5-yl)-6-methyl-1,4-dihydropyrimidine-5-carboxamide
• CAS: 874119-96-7
• 化学式: C₂₆H₂₁ClF₂N₆O₂
• 分子量: 522.942
• InChiKey: DSPVWAIHVFERDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-(6-fluoro-1H-indazol-5-yl)-3-oxobutanamide 、 2-Ethoxypyridine-4-carboximidamide 、 4-氯-2-氟苯甲醛 在 potassium acetate 作用下， 以 二甲基亚砜 为溶剂， 反应 3.0h， 生成 4-(4-chloro-2-fluorophenyl)-2-(2-ethoxypyridin-4-yl)-N-(6-fluoro-1H-indazol-5-yl)-6-methyl-1,4-dihydropyrimidine-5-carboxamide
  参考文献：
  名称：

  Potent, Selective and Orally Bioavailable Dihydropyrimidine Inhibitors of Rho Kinase (ROCK1) as Potential Therapeutic Agents for Cardiovascular Diseases

  摘要：

  Recent studies using known Rho-associated kinase isoform 1 (ROCK1) inhibitors along with cellular and molecular biology data have revealed a pivotal role of this enzyme in many aspects of cardiovascular function. Here we report a series of ROCK 1 inhibitors which were originally derived from a dihydropyrimidinone core 1. Our efforts focused oil the optimization of dihydropyrimidine 2. which resulted in the identification of a series of dihydropyrimidines with improved pharmacokinetics and P450 properties.

  DOI：

  10.1021/jm8005096

文献信息

• Novel Inhibitors of Rho-Kinases
  申请人：Sehon Clark A.

  公开号：US20080125427A1

  公开（公告）日：2008-05-29

  Novel inhibitors of Rho-kinases are disclosed.

  披露了Rho-kinases的新型抑制剂。
• Potent, Selective and Orally Bioavailable Dihydropyrimidine Inhibitors of Rho Kinase (ROCK1) as Potential Therapeutic Agents for Cardiovascular Diseases
  作者：Clark A. Sehon、Gren Z. Wang、Andrew Q. Viet、Krista B. Goodman、Sarah E. Dowdell、Patricia A. Elkins、Simon F. Semus、Christopher Evans、Larry J. Jolivette、Robert B. Kirkpatrick、Edward Dul、Sanjay S. Khandekar、Tracey Yi、Lois L. Wright、Gary K. Smith、David J. Behm、Ross Bentley、Christopher P. Doe、Erding Hu、Dennis Lee

  DOI：10.1021/jm8005096

  日期：2008.11.13

  Recent studies using known Rho-associated kinase isoform 1 (ROCK1) inhibitors along with cellular and molecular biology data have revealed a pivotal role of this enzyme in many aspects of cardiovascular function. Here we report a series of ROCK 1 inhibitors which were originally derived from a dihydropyrimidinone core 1. Our efforts focused oil the optimization of dihydropyrimidine 2. which resulted in the identification of a series of dihydropyrimidines with improved pharmacokinetics and P450 properties.