Phenylacetic acid, 3,5-dibenzyloxy-, benzyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Phenylacetic acid, 3,5-dibenzyloxy-, benzyl ester
• 英文别名: benzyl 2-[3,5-bis(phenylmethoxy)phenyl]acetate
• 化学式: C₂₉H₂₆O₄
• 分子量: 438.523
• InChiKey: DPQRKMLHCZALCI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Phenylacetic acid, 3,5-dibenzyloxy-, benzyl ester 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成 2-[3,5-bis(benzyloxy)phenyl]ethanol
  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：

  (3,5-二甲氧基苯基)乙酸 在 氢溴酸 、 potassium carbonate 作用下， 以 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成 Phenylacetic acid, 3,5-dibenzyloxy-, benzyl ester
  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

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。
• 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.
• US9611213B2
  申请人：——

  公开号：US9611213B2

  公开（公告）日：2017-04-04
• [EN] RESCORCINOLS, METHODS FOR THEIR MANUFACTURE, AND USES THEREOF<br/>[FR] RÉSORCINOLS, LEURS PROCÉDÉS DE FABRICATION ET LEURS UTILISATIONS
  申请人：[en]GW RESEARCH LIMITED

  公开号：WO2022238707A1

  公开（公告）日：2022-11-17

  The present invention relates to a group of resorcinol derivatives as a pharmaceutically active compounds and methods of preparation thereof. Resorcinol derivatives have been used to treat various diseases and disorders. While such treatments hold promise, there remains a need in the art for more effective treatments and this has been brought about by way of the resorcinol derivative of the invention.