噻加宾乙酯 | 145821-58-5

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 噻加宾乙酯
• 英文名称: ethyl (R)-1-<4,4-bis(3-methyl-2-thienyl)-3-butenyl>-3-piperidinecarboxylate
• 英文别名: tiagabine ethyl ester hydrochloride；ethyl (R)-1-(4,4-bis(3-methylthiophen-2-yl)but-3-en-1-yl)piperidine-3-carboxylate；ethyl (3R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]hexahydro-3-pyridinecarboxylate；(R)-tiagabine ethyl ester；tiagabine ethyl ester；ethyl (3R)-1-[4,4-bis(3-methylthiophen-2-yl)but-3-enyl]piperidine-3-carboxylate
• CAS: 145821-58-5
• 化学式: C₂₂H₂₉NO₂S₂
• 分子量: 403.61
• InChiKey: NSGCWILIYQUGIO-GOSISDBHSA-N

物化性质

• 沸点：
  534.8±50.0 °C(Predicted)
• 密度：
  1.144±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  86
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  噻加宾乙酯 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 噻加宾
  参考文献：
  名称：

  The synthesis of novel GABA uptake inhibitors. 1. Elucidation of the structure-activity studies leading to the choice of (R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid (Tiagabine) as an anticonvulsant drug candidate

  摘要：

  A series of different synthetic approaches to novel GABA uptake inhibitors are described, leading to examples which are derivatives of nipecotic acid and guvacine, substituted at nitrogen by 4,4-diaryl-3-butenyl or 2-(diphenylmethoxy)ethyl moieties. The in vitro value for inhibition of [H-3]-GABA uptake in rat synaptosomes was determined for each compound. It was found that the most potent examples are those having a substituent in an ''ortho'' position in one or both aromatic/heteroaromatic groups. The majority of the compounds described are structurally related to tiagabine, (R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid hydrochloride (NNC 05-0328) and some of the reasoning behind the selection of this compound as a drug candidate is summarized.

  DOI：

  10.1021/jm00064a005
• 作为产物：
  描述：

  生成 噻加宾乙酯
  参考文献：
  名称：

  噻加宾的制备方法及其前体化合物

  摘要：

  本发明涉及噻加宾的制备方法及其前体化合物。具体公开了一种噻加宾及其消旋体和S-构型产物的制备方法，其特征在于其中包括使化学式V的化合物与化学式VI的化合物反应制备化学式VII的化合物的步骤： 其中，X选自由氯、溴和碘组成的组中；R 1 为选自由氢、取代或未取代的烷基、取代或未取代的芳基组成的组中的基团，优选为氢、C1-C4烷基或苄基，更优选为氢、甲基、乙基或苄基。本发明的方法通过改变手性哌啶甲酸酯的烷基化方法，利用酰基化转变完成烷基化，从而大大提高手性哌啶甲酸酯的利用率，保持整个N-烷基化总收率80％以上。

  公开号：

  CN102827152A

文献信息

• Cobalt-Catalyzed 1,1-Diboration of Terminal Alkynes: Scope, Mechanism, and Synthetic Applications
  作者：Simon Krautwald、Máté J. Bezdek、Paul J. Chirik

  DOI：10.1021/jacs.7b00445

  日期：2017.3.15

  A cobalt-catalyzed method for the 1,1-diboration of terminal alkynes with bis(pinacolato)diboron (B2Pin2) is described. The reaction proceeds efficiently at 23 °C with excellent 1,1-selectivity and broad functional group tolerance. With the unsymmetrical diboron reagent PinB-BDan (Dan = naphthalene-1,8-diaminato), stereoselective 1,1-diboration provided products with two boron substituents that exhibit

  描述了一种用双 (频哪醇) 二硼 (B2Pin2) 对末端炔烃进行 1,1-二硼化的钴催化方法。该反应在 23 °C 下高效进行，具有出色的 1,1-选择性和广泛的官能团耐受性。使用不对称二硼试剂 PinB-BDan（Dan = naphthalene-1,8-二氨基），立体选择性 1,1-二硼化提供了具有两个硼取代基的产物，这些硼取代基表现出不同的反应性。一个由 1-辛炔二硼化制备的例子被结晶，其立体化学通过 X 射线晶体学确定。1,1-二硼基烯烃产品的实用性和多功能性在许多合成应用中得到了证明，包括癫痫药物tiagabine的简明合成。此外，1,1,1-三硼烷烃的合成是通过钴催化的 1 硼氢化反应完成的，具有 HBPin 的 1-二硼基烯烃。氘标记和化学计量实验支持一种机制，包括将炔基硼酸酯选择性插入硼酸钴络合物的 Co-B 键以形成乙烯基钴中间体。后者被分离出来，并通过核磁共振光谱和
• A convergent approach to (R)-Tiagabine by a regio- and stereocontrolled hydroiodination of alkynes
  作者：Giuseppe Bartoli、Roberto Cipolletti、Giustino Di Antonio、Riccardo Giovannini、Silvia Lanari、Mauro Marcolini、Enrico Marcantoni

  DOI：10.1039/c005042c

  日期：——

  The occurrence of unsaturated systems in natural products combined with the mildness and the wide range of applicability of CeCl3 promoted methodologies suggest several potential future synthetic applications within the field of total synthesis of biologically active molecules. On this concept, the use of CeCl3·7H2O–NaI system as an efficient heterogeneous promoter has been highlighted in the iodofunctionalization of carbon–carbon triple bonds. The study has shown that this method would be particularly interesting for the stereoselective formation of trisubstituted (Z)- or (E)-iodoalkenes by simply changing the nature of the solvent. The methodology has been successfully applied to the synthesis of (R)-1-[4,4-bis-(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid 1, named (R)-Tiagabine, which is a potent and selective γ-aminobutyric acid (GABA) uptake inhibitor with proven anticonvulsant efficacy in humans.

  不饱和体系在天然产物中的出现，以及CeCl3促进的方法所具有的温和性和广泛的适用性，提示在生物活性分子的全合成领域存在多个潜在的未来合成应用。在这个概念下，使用CeCl3·7H2O–NaI体系作为有效的异相促进剂，在碳-碳三重键的碘功能化中得到了强调。研究表明，这种方法对于立体选择性合成三取代的（Z）或（E）碘烯特别有趣，只需改变溶剂的性质。该方法已成功应用于合成（R）-1-[4,4-双-(3-甲基-2-噻吩基)-3-丁烯基]-3-哌啶甲酸1，即（R）-Tiagabine，这是一种有效且选择性的γ-氨基丁酸（GABA）摄取抑制剂，在人类中具有经过验证的抗癫痫疗效。
• N-(butenyl substituted) azaheterocyclic carboxylic acids
  申请人：Novo Nordisk A/S.

  公开号：US05010090A1

  公开（公告）日：1991-04-23

  1-Aminobut-3-en derivatives having optionally substituted furanyl, thienyl, pyridyl and/or pyrrolyl in the 4-position and 3-carboxypiperidin-1-yl, 3-carboxytetrahydropyrid-1-yl or 3 carboxymethylpyrrolidin-1-yl in the 1-position potentiate GABA-ergic neurotransmission.

  在1-位置具有3-羧基哌啶-1-基，3-羧基四氢吡啶-1-基或3-羧甲基吡咯烷-1-基，并在4-位置上选择性地取代呋喃基，噻吩基，吡啶基和/或吡咯基的1-氨基丁-3-烯衍生物，能够增强GABA能神经递质的传递。
• Process for Preparation of Piperidine Carboxylic Acid
  申请人：Bose Prosenjit

  公开号：US20080269495A1

  公开（公告）日：2008-10-30

  A process for preparing pure tiagabine, which is a piperidine carboxylic acid compound, via pharmaceutically acceptable salts of tiagabine ester is provided. Also, L(+) tartaric acid, oxalic acid and dibenzoyl L(+) tartaric acid salts of tiagabine esters are provided. Further, process for preparing acid addition salts of tiagabine esters is provided.

  提供了一种通过苯甲酸酯的药学可接受盐制备纯的哌啶羧酸类化合物替加巴的方法。此外，还提供了替加巴酯的L(+)酒石酸盐、草酸盐和二苯乙酰基L(+)酒石酸盐。此外，还提供了制备替加巴酯酸盐的方法。
• PROCESS FOR PREPARATION OF PIPERIDINE CARBOXYLIC ACID
  申请人：BOSE Prosenjit

  公开号：US20100305328A1

  公开（公告）日：2010-12-02

  Processes for preparing pure tiagabine, a piperidine carboxylic acid, using pharmaceutically acceptable acid addition salts of tiagabine esters are provided. L(+)-tartaric acid, oxalic acid and dibenzoyl L(+)-tartaric acid addition salts of tiagabine esters are also provided. Further, processes for preparing acid addition salts of tiagabine esters are provided.

  本发明提供使用药用可接受的酸加盐的tiagabine酯制备纯tiagabine的过程。同时提供L(+)-酒石酸、草酸和dibenzoyl L(+)-酒石酸的tiagabine酯加盐。此外，还提供制备tiagabine酯酸加盐的过程。