[(1R,3S)-3-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]cyclopentyl] methanesulfonate | 1007306-66-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 英文名称: [(1R,3S)-3-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]cyclopentyl] methanesulfonate
• CAS: 1007306-66-2
• 化学式: C₁₂H₂₃NO₅S
• 分子量: 293.384
• InChiKey: BRDLBNLSNDFYRS-VHSXEESVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  90.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [(1R,3S)-3-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]cyclopentyl] methanesulfonate 、 6-羟基异喹啉-1(2H)-酮 在 PS-BEMP 作用下， 以 乙腈 为溶剂， 生成
  参考文献：
  名称：

  Optimisation of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors

  摘要：

  Rho kinase is an important target implicated in a variety of cardiovascular diseases. Herein, we report the optimisation of the fragment derived ATP-competitive ROCK inhibitors 1 and 2 into lead compound 14A. The initial goal of improving ROCK-I potency relative to 1, whilst maintaining a good PK profile, was achieved through removal of the aminoisoquinoline basic centre. Lead 14A was equipotent against both ROCK-I and ROCK-II, showed good in vivo efficacy in the spontaneous hypertensive rat model, and was further optimised to demonstrate the scope for improving selectivity over PKA versus hydroxy Fasudil 3. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.104

文献信息

• US7893088B2
  申请人：——

  公开号：US7893088B2

  公开（公告）日：2011-02-22
• Optimisation of 6-substituted isoquinolin-1-amine based ROCK-I inhibitors
  作者：Peter Ray、Jane Wright、Julia Adam、Sylviane Boucharens、Darcey Black、Angus R. Brown、Ola Epemolu、Dan Fletcher、Margaret Huggett、Phil Jones、Steven Laats、Amanda Lyons、Jos de Man、Richard Morphy、Brad Sherborne、Lorcan Sherry、Nicole van Straten、Paul Westwood、Mark York

  DOI：10.1016/j.bmcl.2010.12.104

  日期：2011.2

  Rho kinase is an important target implicated in a variety of cardiovascular diseases. Herein, we report the optimisation of the fragment derived ATP-competitive ROCK inhibitors 1 and 2 into lead compound 14A. The initial goal of improving ROCK-I potency relative to 1, whilst maintaining a good PK profile, was achieved through removal of the aminoisoquinoline basic centre. Lead 14A was equipotent against both ROCK-I and ROCK-II, showed good in vivo efficacy in the spontaneous hypertensive rat model, and was further optimised to demonstrate the scope for improving selectivity over PKA versus hydroxy Fasudil 3. (c) 2010 Elsevier Ltd. All rights reserved.