(R)-tert-butyl 4-((methylsulfonyl)oxy)azepane-1-carboxylate | 1309044-57-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环庚烷
• 英文名称: (R)-tert-butyl 4-((methylsulfonyl)oxy)azepane-1-carboxylate
• CAS: 1309044-57-2
• 化学式: C₁₂H₂₃NO₅S
• 分子量: 293.384
• InChiKey: WXGIMXRYMZMWQR-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.75
• 重原子数：
  19.0
• 可旋转键数：
  2.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  72.91
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (R)-tert-butyl 4-((methylsulfonyl)oxy)azepane-1-carboxylate 在 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-tert-butyl 4-((2-(tert-butyl)-6-chlorobenzo[d]oxazol-7-yl)sulfonyl)azepane-1-carboxylate
  参考文献：
  名称：

  Discovery of CNS Penetrant CXCR2 Antagonists for the Potential Treatment of CNS Demyelinating Disorders

  摘要：

  Structure-activity relationship exploration of the historical biarylurea series led to the identification of novel CNS penetrant CXCR2 antagonists with nanomolar potency, favorable PK profile, and good developability potentials. More importantly, the key compound 22 showed efficacy in a cuprizone-induced demyelination model with twice daily oral administration, thereby supporting CXCR2 to be a potential therapeutic target for the treatment of demyelinating diseases such as multiple sclerosis.

  DOI：

  10.1021/acsmedchemlett.5b00489
• 作为产物：
  描述：

  (R)-tert-butyl 4-hydroxyazepane-1-carboxylate 、 甲基磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以1.5 g的产率得到(R)-tert-butyl 4-((methylsulfonyl)oxy)azepane-1-carboxylate
  参考文献：
  名称：

  Discovery of CNS Penetrant CXCR2 Antagonists for the Potential Treatment of CNS Demyelinating Disorders

  摘要：

  Structure-activity relationship exploration of the historical biarylurea series led to the identification of novel CNS penetrant CXCR2 antagonists with nanomolar potency, favorable PK profile, and good developability potentials. More importantly, the key compound 22 showed efficacy in a cuprizone-induced demyelination model with twice daily oral administration, thereby supporting CXCR2 to be a potential therapeutic target for the treatment of demyelinating diseases such as multiple sclerosis.

  DOI：

  10.1021/acsmedchemlett.5b00489

文献信息

• 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.