methyl exo-3-azabicyclo[3.1.0]hexane-6-carboxylate hydrochloride | 1024038-72-9

• 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: methyl exo-3-azabicyclo[3.1.0]hexane-6-carboxylate hydrochloride
• 英文别名: (1R,5S,6r)-methyl 3-azabicyclo[3.1.0]hexane-6-carboxylate
• CAS: 1024038-72-9
• 化学式: C₇H₁₁NO₂
• mdl: MFCD19160626
• 分子量: 141.17
• InChiKey: LITPBZMWZQGLEL-FMCRUOTFSA-N

物化性质

• 沸点：
  192.9±33.0 °C(Predicted)
• 密度：
  1.165±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  10.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.857
• 拓扑面积：
  38.33
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  methyl exo-3-azabicyclo[3.1.0]hexane-6-carboxylate hydrochloride 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 50.0h， 生成 methyl (1R,5S,6s)-3-(5-cyano-6-((2S,3R)-3-hydroxy-2-methylazetidin-1-yl)-4-(trifluoromethyl)pyridin-2-yl)-3-azabicyclo[3.1.0]-hexane-6-carboxylate
  参考文献：
  名称：

  Discovery of PF-06835919: A Potent Inhibitor of Ketohexokinase (KHK) for the Treatment of Metabolic Disorders Driven by the Overconsumption of Fructose

  摘要：

  Increased fructose consumption and its subsequent metabolism have been implicated in metabolic disorders such as nonalcoholic fatty liver disease and steatohepatitis (NAFLD/NASH) and insulin resistance. Ketohexokinase (KHK) converts fructose to fructose-1-phosphate (F1P) in the first step of the metabolic cascade. Herein we report the discovery of a first-in-class KHK inhibitor, PF-06835919 (8), currently in phase 2 clinical trials. The discovery of 8 was built upon our originally reported, fragment-derived lead 1 and the recognition of an alternative, rotated binding mode upon changing the ribose-pocket binding moiety from a pyrrolidinyl to an azetidinyl ring system. This new binding mode enabled efficient exploration of the vector directed at the Arg-108 residue, leading to the identification of highly potent 3-azabicyclo[3.1.0]hexane acetic acid-based KHK inhibitors by combined use of parallel medicinal chemistry and structure-based drug design.

  DOI：

  10.1021/acs.jmedchem.0c00944

文献信息

• CHEMICAL COMPOUNDS
  申请人：McCoull William

  公开号：US20080269288A1

  公开（公告）日：2008-10-30

  Compounds of formula (I): wherein variable groups are defined within; their use in the inhibition of 11βHSD1, processes for making them and pharmaceutical compositions comprising them are described.

  公式（I）的化合物：其中变量基团在内部定义；描述了它们在抑制11βHSD1中的应用，制备它们的过程以及包含它们的药物组合物。
• PYRIDINE CARBOXAMIDES AS 11-BETA-HSD1 INHIBITORS
  申请人：AstraZeneca AB

  公开号：EP2086939B1

  公开（公告）日：2010-07-28
• Chemical compounds
  申请人：AstraZeneca AB

  公开号：EP2233480B1

  公开（公告）日：2013-05-29
• PYRIDINYL SULFONAMIDE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
  申请人：Boehringer Ingelheim International GmbH

  公开号：US20210353608A1

  公开（公告）日：2021-11-18

  The invention relates to new pyridinyl sulfonamide derivatives of the formula wherein R 1 , A and n are as defined herein, to their use as medicaments, to methods for their therapeutic use and to pharmaceutical compositions containing them.
• US7964618B2
  申请人：——

  公开号：US7964618B2

  公开（公告）日：2011-06-21