3-氧代氮杂丁烷-1-羧酸乙酯 | 105258-88-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环丁烷
• 中文名称: 3-氧代氮杂丁烷-1-羧酸乙酯
• 中文别名: 1-氮杂环丁烷甲酸,3-氧代-,乙基酯
• 英文名称: 3-oxo-azetidine-1-carboxylic acid ethyl ester
• 英文别名: 3-oxoazetidine-1-carboxylic acid ethyl ester；N-(ethoxycarbonyl)azetidin-3-one；1-ethoxycarbonylazetidin-3-one；N-ethoxycarbonylazetidin-3-one；Ethyl 3-oxoazetidine-1-carboxylate
• CAS: 105258-88-6
• 化学式: C₆H₉NO₃
• mdl: MFCD00964541
• 分子量: 143.142
• InChiKey: VKIUSHWWSLISPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.666
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  3-氧代氮杂丁烷-1-羧酸乙酯 在 samarium diiodide 作用下， 以 四氢呋喃 为溶剂， 反应 8.0h， 以70%的产率得到N,N-bis(ethoxycarbonyl)-3-hydroxy-3-(3'-hydroxy-3'-azetidinyl)azetidine
  参考文献：
  名称：

  Samarium Iodide Promoted Coupling of N-Substituted Azetidin-3-ones. A Novel Route to Spiroannulated Heterocyclic Oxiranes

  摘要：

  DOI：

  10.3987/com-98-s10
• 作为产物：
  描述：

  N-(ethoxycarbonyl)-3-(bromomethylene)azetidine 在 臭氧 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以70%的产率得到3-氧代氮杂丁烷-1-羧酸乙酯
  参考文献：
  名称：

  N-（乙氧羰基）-3-卤-3-（卤甲基）氮杂环丁烷与DBU的反应。卤素舞。

  摘要：

  N-（乙氧羰基）-3-（溴甲基）-3-氯氮杂环丁烷（3）与DBU的反应导致形成两个卤代烯烃，即N-（乙氧羰基）-3-（溴亚甲基）氮杂环丁烷和N-（乙氧羰基） -3-（氯亚甲基）氮杂环丁烷（分别为4a和4b）。对照实验结果表明，Cl（-）能够促进3和N-（乙氧基羰基）-3-bromo-3-（溴甲基）氮杂环丁烷的CH（2）Br基中溴的亲核取代（8） ，但Br（-）无法取代N-（乙氧羰基）-3-氯-3-（氯甲基）氮杂环丁烷（7）和N-carbethoxy-3-bromo-3的CH（2）Cl基团中的氯-（氯甲基）氮杂环丁烷（10）。因此，建议通过3与DBU的反应形成4b是DBU促进从关键反应中间体7中除去HCl的结果。

  DOI：

  10.1021/jo970166r

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。
• Pharmaceutically active compounds
  申请人：Astra Pharmaceuticals Limited

  公开号：US05883102A1

  公开（公告）日：1999-03-16

  Compounds of formula (I) wherein: R.sup.1 and R.sup.19 independently represent hydrogen, alkyl C1-6, alkoxy C1-6, alkylthio C1-6, halogen, hydroxyl or amino; R.sup.2 represents H or alkyl; R.sup.3 represents phenyl, a 6-membered heterocyclic aromatic ring containing one or two nitrogen atoms, or a 5-membered heterocyclic aromatic ring containing 1 to 3 heteroatoms selected from O,N, and S, which phenyl or heterocyclic aromatic ring may be optionally substituted by alkyl C1-6, alkoxy C1-6, haologen, hydroxyl, alkylthio C1-6, cyano, trifluoromethyl, nitro, hydroxymethyl, amino, a group --(CH.sub.2).sub.c NHCO.sub.2 R.sup.10, a group --(CH.sub.2).sub.c NR.sup.5 R.sup.6, or a group --CO.sub.2 R.sup.11 ; or R.sup.3 represents hydrogen or alkyl C1-8, which alkyl group may be optionally substituted by amino or a group --NHCO.sub.2 R.sup.10 ; R.sup.4 represents hydrogen or alkyl C1-6; or R.sup.3 and R.sup.4 taken together represent a group (CH.sub.2).sub.a Z(CH.sub.2).sub.b ; c represents an integer 0 to 2; and pharmaceutically acceptable salts thereof, have been found to be useful as a pharmaceuticals. The compounds may especially be used in the treatment of inflammatory disorders.

  化学式为（I）的化合物，其中：R.sup.1和R.sup.19分别表示氢，烷基C1-6，烷氧基C1-6，烷硫基C1-6，卤素，羟基或氨基；R.sup.2表示H或烷基；R.sup.3表示苯基，含有一个或两个氮原子的6元杂环芳香环，或含有1至3个杂原子（选自O，N和S）的5元杂环芳香环，其中苯基或杂环芳香环可以选择地由烷基C1-6，烷氧基C1-6，卤素，羟基，烷硫基C1-6，氰基，三氟甲基，硝基，羟甲基，氨基，--（CH.sub.2）.sub.c NHCO.sub.2 R.sup.10，--（CH.sub.2）.sub.c NR.sup.5 R.sup.6或--CO.sub.2 R.sup.11的基团取代；或R.sup.3表示氢或烷基C1-8，所述烷基可以选择地由氨基或--NHCO.sub.2 R.sup.10的基团取代；R.sup.4表示氢或烷基C1-6；或R.sup.3和R.sup.4一起表示(CH.sub.2).sub.a Z(CH.sub.2).sub.b的基团；c表示整数0至2；以及其药学上可接受的盐，已被发现可以用作药物。这些化合物可以特别用于治疗炎症性疾病。
• 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。
• Discovery of KLS-13019, a Cannabidiol-Derived Neuroprotective Agent, with Improved Potency, Safety, and Permeability
  作者：William A. Kinney、Mark E. McDonnell、Hua Marlon Zhong、Chaomin Liu、Lanyi Yang、Wei Ling、Tao Qian、Yu Chen、Zhijie Cai、Dean Petkanas、Douglas E. Brenneman

  DOI：10.1021/acsmedchemlett.6b00009

  日期：2016.4.14

  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.
• [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