(1R)-8-氮杂双环[3.2.1]辛-2-烯-2-羧酸 | 150283-68-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: (1R)-8-氮杂双环[3.2.1]辛-2-烯-2-羧酸
• 英文名称: anhydronorecgonine
• 英文别名: (1R,5S)-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylic acid
• CAS: 150283-68-4
• 化学式: C₈H₁₁NO₂
• 分子量: 153.181
• InChiKey: ZAZOGAHQAWUCJK-IYSWYEEDSA-N

物化性质

• 熔点：
  254 °C
• 沸点：
  317.7±30.0 °C(Predicted)
• 密度：
  1.250±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  甲醇 、 (1R)-8-氮杂双环[3.2.1]辛-2-烯-2-羧酸 在 三氟化硼乙醚 作用下， 反应 4.0h， 生成 anhydronorecgonine methyl ester
  参考文献：
  名称：

  Studies on Hydrolytic and Oxidative Metabolic Pathways of Anhydroecgonine Methyl Ester (Methylecgonidine) Using Microsomal Preparations from Rat Organs

  摘要：

  During smoking of cocaine-base (crack), anhydroecgonine methyl ester (AEME, methylecgonidine) is formed in large amounts as a pyrolysis product of cocaine and is absorbed in the lungs. The metabolism of AEME was studied in the present investigation using microsome preparations from rat liver, lung, kidney, and brain. Potential metabolites of AEME were synthesized and used as substrate to complement the experiments. Analysis of the incubation mixtures was performed using gas chromatography-mass spectrometry and nanoelectrospray multiple-stage mass spectrometry. Screening for metabolites was focused on postulated oxidative pathways, chemical and enzymatic hydrolysis, and ethanol dependent transesterification as known from cocaine metabolism. Enzymatic hydrolysis of AEME to anhydroecgonine (AE), which was inhibited by sodium fluoride, was found in all microsomal preparations. Liver microsomes exhibited the highest activity, brain microsomes the lowest. Anhydronorecgonine methyl ester (ANEME) and anhydroecgonine methyl ester N-oxide were identified as AEME metabolites of liver and lung microsomes only. In the presence of ethanol AEME was metabolized to anhydroecgonine ethyl ester and anhydronorecgonine ethyl ester. Further metabolism of AE or ANEME was not observed. No N-hydroxy-anhydronorecgonine derivatives were found which could represent precursors of cytotoxic metabolites as known to be formed from cocaine.

  DOI：

  10.1021/tx0255828
• 作为产物：
  描述：

  (R)-2-carbomethoxy-3-tropinone 在 盐酸 、 sodium tetrahydroborate 、 三氯氧磷 作用下， 生成 (1R)-8-氮杂双环[3.2.1]辛-2-烯-2-羧酸
  参考文献：
  名称：

  用于肽结构功能研究的Fmoc保护的基于托烷的氨基酸

  摘要：

  已经制备了来自烷烃生物碱核的环状氨基酸，并将其掺入合成肽中。这些构象受限的β-氨基酸在开发生物活性肽的新型合成类似物方面具有相当大的潜力。

  DOI：

  10.1016/s0040-4039(97)00500-5

文献信息

• Monoclonal antibodies specific for crack cocaine metabolites, a cell line producing the same, and crack cocaine conjugates
  申请人：Lu T. Natalie

  公开号：US20050026303A1

  公开（公告）日：2005-02-03

  A monoclonal antibody, and a cell line capable of producing the same, has been produced with the ability to detect the primary metabolites generated from the pyrolysis of smokeable, or “crack”, cocaine. This monoclonal antibody, while being highly specific for anhydroecgonine methyl ester (AEME) and ecgonidine (ECD), does not cross-react at a significant level with the primary cocaine metabolites of powdered or injected cocaine. Also, crack cocaine conjugates capable of evoking an immune response in animals have been produced.

  一种单克隆抗体以及能够产生同种抗体的细胞系已被生产出来，这种抗体能够检测出从可吸烟的或“霹雳”可卡因的热解中生成的主要代谢物。这种单克隆抗体对去氢古柯碱甲酯（AEME）和古柯宁（ECD）具有高度特异性，但与粉状或注射用可卡因的主要代谢物没有显著交叉反应。此外，已经生产出了能够引起动物免疫反应的霹雳可卡因结合物。
• [EN] NITRIC OXIDE RELEASING PRODRUGS OF THERAPEUTIC AGENTS<br/>[FR] PROMÉDICAMENTS D'AGENTS THÉRAPEUTIQUES LIBÉRANT DE L'OXYDE NITRIQUE
  申请人：SATYAM APPARAO

  公开号：WO2014111957A1

  公开（公告）日：2014-07-24

  The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents wherein the drug or therapeutic agents contain at least one carboxylic acid group. The invention also relates to processes for the preparation of these nitric oxide releasing prodrugs, to pharmaceutical compositions containing them and to methods of using these prodrugs.

  本发明涉及已知药物或治疗剂的一氧化氮释放前药，其中所述药物或治疗剂至少含有一个羧酸基团。发明还涉及制备这些一氧化氮释放前药的方法，包含它们的药物组合物以及使用这些前药的方法。
• Nitric Oxide Releasing Prodrugs of Therapeutic Agents
  申请人：SATYAM Apparao

  公开号：US20110263526A1

  公开（公告）日：2011-10-27

  The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents which are represented herein as compounds of formula (I) wherein the drugs or therapeutic agents contain one or more functional groups independently selected from a carboxylic acid, an amino, a hydroxyl and a sulfhydryl group. The invention also relates to processes for the preparation of the nitric oxide releasing prodrugs (the compounds of formula (I)), to pharmaceutical compositions containing them and to methods of using the prodrugs.

  本发明涉及已知药物或治疗剂的一氧化氮释放前药，其在此处表示为式(I)的化合物，其中药物或治疗剂包含一个或多个功能基团，独立地选自羧酸、氨基、羟基和巯基。该发明还涉及制备一氧化氮释放前药（式(I)的化合物）的方法，含有它们的药物组合物以及使用这些前药的方法。
• Crosslinked hyaluronic acid compositions for tissue augmentation
  申请人：Sadozai K. Khalid

  公开号：US20050136122A1

  公开（公告）日：2005-06-23

  A hyaluronic acid (HA) composition includes crosslinked, water-insoluble, hydrated HA gel particles. The HA includes crosslinks represented by the following structural formula: HA—U—R 2 —U—HA The variables are defined herein. A method of augmenting tissue in a subject includes inserting a needle into a subject at a location in the subject that is in need of tissue augmentation, wherein the needle is coupled to a syringe loaded with the HA composition, and applying force to the syringe, to deliver the HA composition into the subject. A method of preparing the HA composition, includes forming water-insoluble, dehydrated crosslinked HA particles, separating the water-insoluble, dehydrated particles by average diameter, selecting a subset of particles by average diameter, and hydrating the subset of dehydrated particles with a physiologically compatible aqueous solution. Another method of preparing the crosslinked HA composition includes crosslinking a precursor of the crosslinked HA with a biscarbodiimide in the presence of a pH buffer and dehydrating the crosslinked HA. Also included is a method of augmenting tissue in a subject that is in need of tissue augmentation. A method of stabilizing crosslinked HA includes hydrating water-insoluble, dehydrated crosslinked HA with a physiologically compatible aqueous solution that includes a local anesthetic, wherein the value of storage modulus G′ for the stabilized composition is at least about 110% of the value of G′ for a non-stabilized composition,. Also included is the stabilized HA composition.

  一种透明质酸（HA）组合物包括交联的、不溶于水的、水合的HA凝胶颗粒。HA包括由以下结构式表示的交联：HA—U—R2—U—HA。变量在此定义。一种在受试者中增强组织的方法包括将针插入受试者体内需要组织增强的位置，其中针连接到装有HA组合物的注射器，并施加力量到注射器，将HA组合物注入受试者体内。一种制备HA组合物的方法包括形成不溶于水的、脱水的交联HA颗粒，通过平均直径分离不溶于水的、脱水的颗粒，通过平均直径选择颗粒的子集，并用生理兼容的水溶液使脱水的颗粒子集水化。另一种制备交联HA组合物的方法包括在pH缓冲剂存在下用双异氰酸酯交联交联HA的前体，并脱水交联HA。还包括一种在需要组织增强的受试者中增强组织的方法。一种稳定交联HA的方法包括用含有局部麻醉剂的生理兼容水溶液水化不溶于水的、脱水的交联HA，其中稳定组合物的存储模量G′的值至少为非稳定组合物G′值的约110%。还包括稳定的HA组合物。
• METHOD FOR PRODUCING (1R,5S) ANHYDROECGONINE ESTER SALTS
  申请人：Puder Carsten H.

  公开号：US20100331544A1

  公开（公告）日：2010-12-30

  The invention relates to a large-scale method for producing salts of (IR,5S) anhydroecgonine esters. The salt formation and selective crystallization of (IR,5S) anhydroecgonine esters with chiral acids is highly efficient in producing an enantiomer form, any undesired enantiomers and other impurities being removed. The ester and its salts are used as the starting material for producing active agents.

  该发明涉及一种大规模生产（IR,5S）缺水异香草碱酯盐的方法。利用手性酸与（IR,5S）缺水异香草碱酯的盐形成和选择性结晶，在生产对映体形式上高效，任何不需要的对映体和其他杂质都被去除。该酯及其盐被用作生产活性剂的起始物质。