3-Cyclohexyl-azetidin | 92145-53-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环丁烷
• 英文名称: 3-Cyclohexyl-azetidin
• 英文别名: 3-cyclohexyl-azetidine；3-Cyclohexylazetidine
• CAS: 92145-53-4
• 化学式: C₉H₁₇N
• 分子量: 139.241
• InChiKey: MTKFRSYJQSSPBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  10
• 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：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-Cyclohexyl-azetidin 、 5-amino-3,4-dimethylthieno[2,3-c]pyridazine-6-carboxylic acid 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (5-Amino-3,4-dimethylthieno[2,3-c]pyridazin-6-yl)-(3-cyclohexylazetidin-1-yl)methanone
  参考文献：
  名称：

  Challenges in the development of an M 4 PAM preclinical candidate: The discovery, SAR, and biological characterization of a series of azetidine-derived tertiary amides

  摘要：

  Herein we describe the continued optimization of M-4 positive allosteric modulators (PAMs) within the 5-amino-thieno[2,3-c] pyridazine series of compounds. In this letter, we disclose our studies on tertiary amides derived from substituted azetidines. This series provided excellent CNS penetration, which had been challenging to consistently achieve in other amide series. Efforts to mitigate high clearance, aided by metabolic softspot analysis, were unsuccessful and precluded this series from further consideration as a preclinical candidate. In the course of this study, we found that potassium tetrafluoroborate salts could be engaged in a tosyl hydrazone reductive cross coupling reaction, a previously unreported transformation, which expands the synthetic utility of the methodology. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.10.053
• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 3-Cyclohexyl-azetidin
  参考文献：
  名称：

  Challenges in the development of an M 4 PAM preclinical candidate: The discovery, SAR, and biological characterization of a series of azetidine-derived tertiary amides

  摘要：

  Herein we describe the continued optimization of M-4 positive allosteric modulators (PAMs) within the 5-amino-thieno[2,3-c] pyridazine series of compounds. In this letter, we disclose our studies on tertiary amides derived from substituted azetidines. This series provided excellent CNS penetration, which had been challenging to consistently achieve in other amide series. Efforts to mitigate high clearance, aided by metabolic softspot analysis, were unsuccessful and precluded this series from further consideration as a preclinical candidate. In the course of this study, we found that potassium tetrafluoroborate salts could be engaged in a tosyl hydrazone reductive cross coupling reaction, a previously unreported transformation, which expands the synthetic utility of the methodology. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.10.053

文献信息

• [EN] NOVEL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2019034702A1

  公开（公告）日：2019-02-21

  The invention relates to compounds of Formula (I) and their use in therapy, for example in the treatment of mycobacterial infections or in the treatment of diseases caused by mycobacterium, such as tuberculosis

  这项发明涉及到式（I）化合物及其在治疗中的应用，例如在治疗分枝杆菌感染或治疗由分枝杆菌引起的疾病，如结核病。
• Compounds
  申请人：GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED

  公开号：US11253499B2

  公开（公告）日：2022-02-22

  The invention relates to compounds of Formula (I) and their use in therapy, for example in the treatment of mycobacterial infections or in the treatment of diseases caused by Mycobacterium, such as tuberculosis.

  本发明涉及式（I）化合物及其在治疗中的应用，例如用于治疗分枝杆菌感染或治疗由分枝杆菌引起的疾病，如结核病。
• NOVEL COMPOUNDS
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：EP3668854B1

  公开（公告）日：2022-01-12
• US9458104B2
  申请人：——

  公开号：US9458104B2

  公开（公告）日：2016-10-04
• Challenges in the development of an M 4 PAM preclinical candidate: The discovery, SAR, and biological characterization of a series of azetidine-derived tertiary amides
  作者：James C. Tarr、Michael R. Wood、Meredith J. Noetzel、Bruce J. Melancon、Atin Lamsal、Vincent B. Luscombe、Alice L. Rodriguez、Frank W. Byers、Sichen Chang、Hyekyung P. Cho、Darren W. Engers、Carrie K. Jones、Colleen M. Niswender、Michael W. Wood、Nicholas J. Brandon、Mark E. Duggan、P. Jeffrey Conn、Thomas M. Bridges、Craig W. Lindsley

  DOI：10.1016/j.bmcl.2017.10.053

  日期：2017.12

  Herein we describe the continued optimization of M-4 positive allosteric modulators (PAMs) within the 5-amino-thieno[2,3-c] pyridazine series of compounds. In this letter, we disclose our studies on tertiary amides derived from substituted azetidines. This series provided excellent CNS penetration, which had been challenging to consistently achieve in other amide series. Efforts to mitigate high clearance, aided by metabolic softspot analysis, were unsuccessful and precluded this series from further consideration as a preclinical candidate. In the course of this study, we found that potassium tetrafluoroborate salts could be engaged in a tosyl hydrazone reductive cross coupling reaction, a previously unreported transformation, which expands the synthetic utility of the methodology. (C) 2017 Elsevier Ltd. All rights reserved.