(1R,2S,5S)-3-azabicyclo[3.1.0]hexan-2-ylmethanol | 72496-52-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (1R,2S,5S)-3-azabicyclo[3.1.0]hexan-2-ylmethanol
• 英文别名: (1R,2S,5S)-Rel-3-azabicyclo[3.1.0]hexane-2-methanol；[(1R,2S,5S)-3-azabicyclo[3.1.0]hexan-2-yl]methanol
• CAS: 72496-52-7
• 化学式: C₆H₁₁NO
• 分子量: 113.159
• InChiKey: SFEYJTLKTWQWMB-HSUXUTPPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(4-((4-((5-methyl-1H-pyrazol-3-yl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)thio)phenyl)acetamide 、 (1R,2S,5S)-3-azabicyclo[3.1.0]hexan-2-ylmethanol 在 N,N-二异丙基乙胺 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 2-[(1R,2S,5S)-2-(hydroxymethyl)-3-azabicyclo[3.1.0]hexan-3-yl]-N-[4-[4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]sulfanylphenyl]acetamide
  参考文献：
  名称：

  Novel series of pyrrolotriazine analogs as highly potent pan-Aurora kinase inhibitors

  摘要：

  The synthesis and SAR for a novel series of pyrrolotriazines as pan-Aurora kinase inhibitors are described. Optimization of the cyclopropane carboxamide terminus of lead compound 1 resulted in analogs with high cellular activity and improved rat PK profiles. Notably, compound 17l demonstrated tumor growth inhibition in a mouse xenograft model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.027
• 作为产物：
  描述：

  (1R,2S,5S)-3-氮杂双环[3.1.0]己烷-2-羧酸 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成 (1R,2S,5S)-3-azabicyclo[3.1.0]hexan-2-ylmethanol
  参考文献：
  名称：

  Novel series of pyrrolotriazine analogs as highly potent pan-Aurora kinase inhibitors

  摘要：

  The synthesis and SAR for a novel series of pyrrolotriazines as pan-Aurora kinase inhibitors are described. Optimization of the cyclopropane carboxamide terminus of lead compound 1 resulted in analogs with high cellular activity and improved rat PK profiles. Notably, compound 17l demonstrated tumor growth inhibition in a mouse xenograft model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.027

文献信息

• CYCLOPROPYL PYRROLIDINE OREXIN RECEPTOR ANTAGONISTS
  申请人：Coleman Paul J.

  公开号：US20100152191A1

  公开（公告）日：2010-06-17

  The present invention is directed to cyclopropyl proline bis-amide compounds which are antagonists of orexin receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及环丙基脯氨酸双酰胺化合物，其为促进睡眠荷尔蒙受体的拮抗剂，并可用于治疗或预防神经和精神障碍以及涉及促进睡眠荷尔蒙受体的疾病。本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及促进睡眠荷尔蒙受体的疾病中的使用。
• Insights of a Lead Optimization Study and Biological Evaluation of Novel 4-Hydroxytamoxifen Analogs as Estrogen-Related Receptor γ (ERRγ) Inverse Agonists
  作者：Jina Kim、Seo Yeon Woo、Chun Young Im、Eun Kyung Yoo、Seungmi Lee、Hyo-Ji Kim、Hee-Jong Hwang、Joong-heui Cho、Won Seok Lee、Heeseok Yoon、Shinae Kim、Oh-bin Kwon、Hayoung Hwang、Kyung-Hee Kim、Jae-Han Jeon、Thoudam Debraj Singh、Sang Wook Kim、Sung Yeoun Hwang、Hueng-Sik Choi、In-Kyu Lee、Seong Heon Kim、Yong Hyun Jeon、Jungwook Chin、Sung Jin Cho

  DOI：10.1021/acs.jmedchem.6b01204

  日期：2016.11.23

  We evaluated the in vitro pharmacology as well as the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of chemical entities that not only were shown to be highly selective agonists for ERR gamma but also exhibited enhanced pharmacokinetic profile compared with 3 (GSK5182). 6g and 10b had comparable potency to 3 and were far more selective for ERR gamma over the ERR alpha, -beta, and ER alpha. The in vivo pharmacokinetic profiles of 6g and 10b were further evaluated, as they possessed superior in vitro ADMET profiles compared to the other compounds. Additionally, we observed a significant increase of fully glycosylated NIS protein, key protein for radioiodine therapy in anaplastic thyroid cancer (ATC), in 6g- or 10b treated CAL62 cells, which indicated that these compounds could be promising enhancers for restoring NIS protein function in ATC cells. Thus, 6g and 10b-possess advantageous druglike properties and can be used to potentially treat various ERR gamma-related disorders.
• US8030495B2
  申请人：——

  公开号：US8030495B2

  公开（公告）日：2011-10-04
• Novel series of pyrrolotriazine analogs as highly potent pan-Aurora kinase inhibitors
  作者：Sunny Abraham、Michael J. Hadd、Lan Tran、Troy Vickers、Janice Sindac、Zdravko V. Milanov、Mark W. Holladay、Shripad S. Bhagwat、Helen Hua、Julia M. Ford Pulido、Merryl D. Cramer、Dana Gitnick、Joyce James、Alan Dao、Barbara Belli、Robert C. Armstrong、Daniel K. Treiber、Gang Liu

  DOI：10.1016/j.bmcl.2011.07.027

  日期：2011.9

  The synthesis and SAR for a novel series of pyrrolotriazines as pan-Aurora kinase inhibitors are described. Optimization of the cyclopropane carboxamide terminus of lead compound 1 resulted in analogs with high cellular activity and improved rat PK profiles. Notably, compound 17l demonstrated tumor growth inhibition in a mouse xenograft model. (C) 2011 Elsevier Ltd. All rights reserved.