ethyl 3-(3,5-dihydroxy-4-((1R,6R)-3-methyl-6-(prop-1-en-2-yl)cyclohex-2-enyl)benzyl)azetidine-1-carboxylate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: ethyl 3-(3,5-dihydroxy-4-((1R,6R)-3-methyl-6-(prop-1-en-2-yl)cyclohex-2-enyl)benzyl)azetidine-1-carboxylate
• 英文别名: KLS-13022；ethyl 3-[[3,5-dihydroxy-4-[(1R,6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]phenyl]methyl]azetidine-1-carboxylate
• 化学式: C₂₃H₃₁NO₄
• 分子量: 385.503
• InChiKey: TUBKEUCTRHMCLI-RBUKOAKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-(3,5-dihydroxy-4-((1R,6R)-3-methyl-6-(prop-1-en-2-yl)cyclohex-2-enyl)benzyl)azetidine-1-carboxylate 在 lithium aluminium tetrahydride 作用下， 以 甲基叔丁基醚 为溶剂， 反应 4.0h， 以56%的产率得到5-[(1-methylazetidin-3-yl)methyl]-2-[(1R,6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]benzene-1,3-diol
  参考文献：
  名称：

  Discovery of KLS-13019, a Cannabidiol-Derived Neuroprotective Agent, with Improved Potency, Safety, and Permeability

  摘要：

  Cannabidiol is the nonpsychoactive natural component of C. sativa that has been shown to be neuroprotective in multiple animal models. Our interest is to advance a therapeutic candidate for the orphan indication hepatic encephalopathy (HE). HE is a serious neurological disorder that occurs in patients with cirrhosis or liver failure. Although cannabidiol is effective in models of HE, it has limitations in terms of safety and oral bioavailability. Herein, we describe a series of side chain modified resorcinols that were designed for greater hydrophilicity and "drug likeness", while varying hydrogen bond donors, acceptors, architecture, basicity, neutrality, acidity, and polar surface area within the pendent group. Our primary screen evaluated the ability of the test agents to prevent damage to hippocampal neurons induced by ammonium acetate and ethanol at clinically relevant concentrations. Notably, KLS-13019 was 50-fold more potent and >400-fold safer than cannabidiol and exhibited an in vitro profile consistent with improved oral bioavailability.

  DOI：

  10.1021/acsmedchemlett.6b00009
• 作为产物：
  描述：

  3-氧代氮杂丁烷-1-羧酸乙酯 在 正丁基锂 、 palladium 10% on activated carbon 、 氢气 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 正己烷 、 氯仿 、 乙酸乙酯 为溶剂， 反应 5.84h， 生成 ethyl 3-(3,5-dihydroxy-4-((1R,6R)-3-methyl-6-(prop-1-en-2-yl)cyclohex-2-enyl)benzyl)azetidine-1-carboxylate
  参考文献：
  名称：

  NOVEL FUNCTIONALIZED 1,3-BENZENE DIOLS AND THEIR METHOD OF USE FOR THE TREATMENT OF HEPATIC ENCEPHALOPTHY

  摘要：

  本发明的药物组合物包括在治疗肝性脑病及相关疾病中具有疾病修饰作用的新型功能化1,3-苯二酚。本发明的药物组合物还包括新型的神经保护剂。

  公开号：

  US20160311769A1

文献信息

• NOVEL FUNCTIONALIZED 1,3-BENZENE DIOLS AND THEIR METHOD OF USE FOR THE TREATMENT OF HEPATIC ENCEPHALOPTHY
  申请人：Kannalife, Inc.

  公开号：US20160311769A1

  公开（公告）日：2016-10-27

  Pharmaceutical compositions of the invention include novel functionalized 1,3-benzenediols having a disease-modifying action in the treatment of hepatic encephalopathy and related conditions. Pharmaceutical compositions of the invention further include novel neuroprotective agents.

  本发明的药物组合物包括在治疗肝性脑病及相关疾病中具有疾病修饰作用的新型功能化1,3-苯二酚。本发明的药物组合物还包括新型的神经保护剂。
• Method for treating hepatic encephalopathy or a disease associated with free radical mediate stress and oxidative stress with novel functionalized 1,3-benzene diols
  申请人：KANNALIFE SCIENCES, INC.

  公开号：US10004722B2

  公开（公告）日：2018-06-26

  Pharmaceutical compositions of the invention include novel functionalized 1,3-benzenediols having a disease-modifying action in the treatment of hepatic encephalopathy and related conditions. Pharmaceutical compositions of the invention further include novel neuroprotective agents.

  本发明的药物组合物包括新型官能化 1,3-苯二酚，在治疗肝性脑病及相关疾病方面具有疾病调节作用。本发明的药物组合物还包括新型神经保护剂。
• [EN] NOVEL FUNCTIONALIZED 1,3-BENZENE DIOLS AND THEIR METHOD OF USE FOR THE TREATMENT OF HEPATIC ENCEPHALOPATHY<br/>[FR] NOUVEAUX 1,3-BENZÈNE DIOLS FONCTIONNALISÉS ET LEUR PROCÉDÉ D'UTILISATION POUR LE TRAITEMENT DE L'ENCÉPHALOPATHIE HÉPATIQUE
  申请人：KANNALIFE INC

  公开号：WO2015106108A3

  公开（公告）日：2015-11-12
• NOVEL FUNCTIONALIZED 1,3-BENZENE DIOLS AND THEIR METHOD OF USE FOR THE TREATMENT OF HEPATIC ENCEPHALOPATHY
  申请人：Kannalife Sciences, Inc.

  公开号：EP3094318B1

  公开（公告）日：2020-02-19
• METHOD FOR TREATING HEPATIC ENCEPHALOPATHY OR A DISEASE ASSOCIATED WITH FREE RADICAL MEDIATE STRESS AND OXIDATIVE STRESS WITH NOVEL FUNCTIONALIZED 1,3-BENZENE DIOLS
  申请人：KANNALIFE SCIENCES, INC.

  公开号：US20170157097A1

  公开（公告）日：2017-06-08

  Pharmaceutical compositions of the invention include novel functionalized 1,3-benzenediols having a disease-modifying action in the treatment of hepatic encephalopathy and related conditions. Pharmaceutical compositions of the invention further include novel neuroprotective agents.