N-[2-hydroxy-3-(6'-pyridin-4-yl-3'-pyrrolidin-1-yl-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl)propyl]acetamide | 1601619-57-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-[2-hydroxy-3-(6'-pyridin-4-yl-3'-pyrrolidin-1-yl-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl)propyl]acetamide
• 英文别名: N-[2-hydroxy-3-[4-(6-pyridin-4-yl-3-pyrrolidin-1-ylpyrazin-2-yl)piperazin-1-yl]propyl]acetamide
• CAS: 1601619-57-1
• 化学式: C₂₂H₃₁N₇O₂
• 分子量: 425.534
• InChiKey: KGKKYNPHBHTGSO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  97.7
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-[2-hydroxy-3-(6'-pyridin-4-yl-3'-pyrrolidin-1-yl-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl)propyl]acetamide 在 盐酸 作用下， 以 乙醚 、 乙酸乙酯 为溶剂， 以19%的产率得到N-[2-hydroxy-3-(6'-pyridin-4-yl-3'-pyrrolidin-1-yl-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl)propyl]acetamide hydrochloride
  参考文献：
  名称：

  In vivo optimization of 2,3-diaminopyrazine Rho Kinase inhibitors for the treatment of glaucoma

  摘要：

  A series of 2,3,6-pyrazine Rho Kinase inhibitors were optimized for in vivo activity for topical ocular dosing. Modifications of the 2-(piperazin-1-yl) pyrazine derivatives produced compounds with improved solubility and physicochemical properties. Modifications of the 6-pyrazine substituent led to improvements in in vitro potency. Compound 9 had the best in vitro and in vivo potency of EC50 = 260 nM with a 30% reduction of IOP in a non-human primate model at a dose of 0.33%. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.017
• 作为产物：
  描述：

  6'-pyridin-4-yl-3'-pyrrolidin-1-yl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl 在 盐酸 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 0.17h， 生成 N-[2-hydroxy-3-(6'-pyridin-4-yl-3'-pyrrolidin-1-yl-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl)propyl]acetamide
  参考文献：
  名称：

  In vivo optimization of 2,3-diaminopyrazine Rho Kinase inhibitors for the treatment of glaucoma

  摘要：

  A series of 2,3,6-pyrazine Rho Kinase inhibitors were optimized for in vivo activity for topical ocular dosing. Modifications of the 2-(piperazin-1-yl) pyrazine derivatives produced compounds with improved solubility and physicochemical properties. Modifications of the 6-pyrazine substituent led to improvements in in vitro potency. Compound 9 had the best in vitro and in vivo potency of EC50 = 260 nM with a 30% reduction of IOP in a non-human primate model at a dose of 0.33%. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.017