芽子碱盐酸盐 | 5796-31-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 中文名称: 芽子碱盐酸盐
• 英文名称: ecgonine hydrochloride
• 英文别名: (1R,2R,3S,5S)-3-hydroxy-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid;hydrochloride
• CAS: 5796-31-6
• 化学式: C₉H₁₅NO₃*ClH
• 分子量: 221.684
• InChiKey: HVWQTEPEBQYIFB-PXXJPSRFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.09
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.888
• 拓扑面积：
  62
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  芽子碱盐酸盐 在 盐酸 、 乙酰氯 作用下， 反应 19.0h， 生成 脱水芽子碱甲基酯甲磺酸盐
  参考文献：
  名称：

  AN IMPROVED PROCEDURE FOR THE SYNTHESIS OF ANHYDROECGONINE METHYL ESTER

  摘要：

  DOI：

  10.1080/00304949709355202
• 作为产物：
  描述：

  古卡因 在 盐酸 、 水 作用下， 反应 20.0h， 以98.42%的产率得到芽子碱盐酸盐
  参考文献：
  名称：

  Method for preparing organoboron derivative containing oxygen and aromatic ring as labeled precursor of dopamine positron emission tomography imaging agent

  摘要：

  揭示了一种制备含氧原子和芳香环的有机硼衍生物作为多巴胺正电子发射断层扫描成像剂的标记前体的方法。可卡因的盐酸盐被用作引发剂。含氧原子的有机硼衍生物直接在芳香环上生成作为药物物质，并且芳香环直接标记了放射性同位素氟-18（F-18）。该方法仅需五个步骤，包括四个步骤用于制备含氧原子和芳香环的有机硼衍生物作为药物物质，以及一步用于直接将有机硼衍生物的芳香环标记为F-18。不仅显著缩短了过程时间，还有效提高了总产率。

  公开号：

  US10934314B1

文献信息

• Anti-cocaine catalytic antibody
  申请人：The Trustees of Columbia University in the City of New York

  公开号：US20030077793A1

  公开（公告）日：2003-04-24

  Disclosed are catalytic antibodies and polypeptides capable of degrading cocaine. Said catalytic antibodies and polypeptides are characterized by the amino acid sequence of their complementary determining regions and framework regions. The present invention also discloses a pharmaceutical composition and a method for decreasing the concentration and a method for decreasing the concentration of cocaine of a subject. Finally, the invention discloses pharmaceutical compositions and methods for treating cocaine overdose and addiction in subjects.

  本发明揭示了能够降解可卡因的催化抗体和多肽。所述催化抗体和多肽的特征在于它们的互补决定区域和框架区域的氨基酸序列。本发明还揭示了一种降低受试者体内可卡因浓度的药物组合物和方法。最后，本发明还揭示了用于治疗受试者可卡因过量和成瘾的药物组合物和方法。
• 2β-Substituted Analogues of 4‘-Iodococaine:  Synthesis and Dopamine Transporter Binding Potencies
  作者：Kwasi S. Avor、Satendra Singh、Thomas W. Seale、Buddy Pouw、Garo P. Basmadjian

  DOI：10.1021/jm980061w

  日期：1998.6.1

  4'-iodococaine (3) was synthesized and evaluated in an in vitro dopamine transporter (DAT) binding assay. Selective hydrolysis at the 2beta-position of 3 gave the carboxylic acid 15 that served as the intermediate for the synthesis of compounds 4, 5, and 6-11. The 2beta-alkyl derivatives were obtained from ecgonine methyl ester (17) through a series of reactions leading to the aldehyde 20. Wittig reaction

  合成了一系列2β-取代的4'-碘多卡因（3）类似物，并在体外多巴胺转运蛋白（DAT）结合测定中进行了评估。在3的2β位选择性水解得到羧酸15，其用作合成化合物4、5和6-11的中间体。2-8烷基衍生物是从芽子碱甲酯（17）通过一系列导致醛20的反应获得的。20与甲基三苯基磷烷的Wittig反应，然后进行氢化和苯甲酰化，得到产物12和13。4'-的结合亲和力碘多卡因（3）比可卡因少10倍。3的羟甲烷，乙酸酯，酰胺，苄基酯，氧化唑和乙烷衍生物显示出降低的结合，而乙烯基，苯基和乙酯显示出适度的结合亲和力。与4'-碘多卡因相比，只有异丙基衍生物8的结合亲和力提高了2倍（3）。8'在2'位的羟基化反应得到14，不仅使DAT的结合力提高了2倍，而且还增强了DAT相对于去甲肾上腺素和5-羟色胺转运蛋白的选择性。在宽剂量范围内，化合物14未能在C57BL / 6J小鼠中刺激运动活性，并阻止了可卡因诱导的运动刺激作用。
• Copper‐mediated nucleophilic radiofluorination of [ ¹⁸ F]β‐CFT for positron emission tomography imaging of dopamine transporter
  作者：Hung‐Man Yu、Ching‐Yun Li、Shiu‐Wen Liu、Chun‐Hung Yang、Yu Chang

  DOI：10.1002/jlcr.3905

  日期：2021.5.30

  [18F]β-CFT is a positron emission tomography (PET) ligand for imaging of dopamine transporter. It was proved to be a sensitive PET marker to detect presynaptic dopaminergic hypofunction in Parkinson's disease. In recent years, copper-mediated 18F-fluorination of aryl boronic esters has been successful in some molecules containing aromatic groups. In this study, we describe the novel synthetic strategy of [18F]β-CFT by copper-mediated nucleophilic radiofluorination with pinacol-derived aryl boronic esters upon reaction with [18F]KF/K222 and Cu (OTf)2(py)4. The radiolabeling protocol was optimized with [18F]fluoride elution method and amount of copper catalyst used. [18F]β-CFT is obtained from boronic ester precursors in 2.2% to 10.6% non-isolated radiochemical yield (RCY). Purified [18F]β-CFT with >99% radiochemical purity (RCP) and high molar activity was obtained in validation runs. The radiolabeling procedure is straightforward and can easily be adapted for clinical use.

  [18F]β-CFT是一种用于多巴胺转运体成像的正电子发射断层扫描（PET）配体。它被证明是检测帕金森病突触前多巴胺能功能减退的灵敏 PET 标志物。近年来，铜介导的芳基硼酸酯 18F 氟化在一些含有芳香基团的分子中取得了成功。在本研究中，我们介绍了铜介导的亲核放射性氟化[18F]β-CFT的新合成策略，该方法是以频哪醇衍生的芳基硼酸酯为原料，与[18F]KF/K222和Cu (OTf)2(py)4反应生成[18F]β-CFT。从硼酸酯前体中获得的[18F]β-CFT 的非分离放射化学收率（RCY）为 2.2% 至 10.6%。在验证运行中，获得了纯化的[18F]β-CFT，其放射化学纯度（RCP）大于 99%，摩尔活性很高。放射性标记过程简单明了，可轻松应用于临床。
• Generation of Polyclonal Catalytic Antibodies Against Cocaine Using Transition State Analogs of Cocaine Conjugated to Diphtheria Toxoid.
  作者：Garo P. BASMADJIAN、Satendra SINGH、Budiono SASTRODJOJO、Blaine T. SMITH、Kwasi AVOR、Fengchun CHANG、Stanley L. MILLS、Thomas W. SEALE

  DOI：10.1248/cpb.43.1902

  日期：——

  Six novel transition state analogs (TSAs) of cocaine (10-14 and 17) and one non-cocaine, p-aminophenyl-phosphonyl ester of cyclohexanol (19), were synthesized and characterized by 1H- and 13C-NMR and FAB-MS.(1R)-ecgonine methyl ester or cyclohexanol were subjected to phenylphosphonylation in the presence of dicyclohexyl carbodiimde (DCC) and 4-N, N-dimethyl aminopyridine (4-DMAP). TSA-IV (10), however, was synthesized from norcocaine which was protected with dibromoethane to yield 4 before acid hydrolysis, esterification and phenyl-phosphonylation were carried out. TSA-III (11) TSA-I (12) and (19), using various length spacer arms, were coupled with the immunogenic protein, diphtheria toxoid (DT). The TSAs coupled with DT were used to immunize mice and after appropriate boosts their sera were tested for the presence and titer of anti-TSA polyclonal antibodies using ELISA. Preliminary results show that the mice immunized with these TSAs produced high titers of polyclonal catalytic antibodies, except for (19), with the ability to hydrolyze the substrate 125I-4'-iodococaine in an in vitro assay, even in the presence of noncatalytic anti-TSA antibodies.

  合成了六种新型可卡因过渡态类似物 (TSA) (10-14 和 17) 和一种非可卡因环己醇对氨基苯基膦酰酯 (19)，并通过 1H 和 13C-NMR 和 FAB-MS 进行表征(1R)-芽子碱甲酯或环己醇在二环己基碳二亚胺(DCC)和4-N，N-二甲基氨基吡啶(4-DMAP)存在下进行苯基膦酰化。然而，TSA-IV (10) 是由去甲可卡因合成的，在进行酸水解、酯化和苯基膦酰化之前，将去甲可卡因用二溴乙烷保护以产生4。 TSA-III (11) TSA-I (12) 和 (19) 使用不同长度的间隔臂与免疫原性蛋白白喉类毒素 (DT) 偶联。 TSA 与 DT 结合用于免疫小鼠，并在适当加强后，使用 ELISA 测试其血清中抗 TSA 多克隆抗体的存在和滴度。初步结果表明，用这些 TSA 免疫的小鼠产生了高滴度的多克隆催化抗体（（19）除外），在体外测定中具有水解底物 125I-4'-碘可卡因的能力，即使在存在非催化抗体的情况下也是如此。 -TSA 抗体。
• [EN] METHODS FOR PRODUCING HYDROXYALKYL TROPANE ESTERS<br/>[FR] PROCÉDÉS DE PRODUCTION D'HYDROXYALKYL TROPANE ESTERS
  申请人：ENTROPIN INC

  公开号：WO2004018464A1

  公开（公告）日：2004-03-04

  This invention provides a method for preparing a hydroxyalkyl tropane ester, comprising: (a) contacting a tropane and 1,1'-carbonyldiimidazole to produce an activated tropane ester; (b) contacting the activated tropane ester with an excess of an alkanediol to form a reaction mixture; and (c) maintaining the reaction mixture at a temperature and for a sufficient time for the activated tropane ester to react with the alkanediol to form the corresponding hydroxyalkyl tropane ester. This method may be used to produce hydroxyalkyl derivatives of tropanes such as benzoylecgonine, ecgonine and ecgonidine.

  本发明提供了一种制备羟基烷基曲柳酯的方法，包括：（a）将曲柳和1,1'-羰基二咪唑接触以产生活化的曲柳酯；（b）将活化的曲柳酯与过量的脂肪二醇接触以形成反应混合物；并且（c）在足够的时间内将反应混合物保持在一定的温度下，使活化的曲柳酯与脂肪二醇反应形成相应的羟基烷基曲柳酯。该方法可用于生产苯甲酰异可卡因、异可卡因和异可吡啶等曲柳酯的羟基烷基衍生物。