6'-pyridin-4-yl-3'-pyrrolidin-1-yl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl | 1217067-69-0

• 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: 6'-pyridin-4-yl-3'-pyrrolidin-1-yl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl
• 英文别名: 3-(Piperazin-1-yl)-5-(pyridin-4-yl)-2-(pyrrolidin-1-yl)pyrazine；3-piperazin-1-yl-5-pyridin-4-yl-2-pyrrolidin-1-ylpyrazine
• CAS: 1217067-69-0
• 化学式: C₁₇H₂₂N₆
• 分子量: 310.402
• InChiKey: GTMYXOHGZNMQRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  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 、 乙醚 、 二氯甲烷 、 乙腈 为溶剂， 生成 N-{3-[3'-(ethylpropylamino)-6'-pyridin-4-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

文献信息

• In vivo optimization of 2,3-diaminopyrazine Rho Kinase inhibitors for the treatment of glaucoma
  作者：Hwang-Hsing Chen、Abdelmoulah Namil、Bryon Severns、Jennifer Ward、Curtis Kelly、Colene Drace、Marsha A. McLaughlin、Shenouda Yacoub、Byron Li、Raj Patil、Naj Sharif、Mark R. Hellberg、Andrew Rusinko、Iok-Hou Pang、Keith D. Combrink

  DOI：10.1016/j.bmcl.2014.03.017

  日期：2014.4

  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.