(S)-methyl 2-(2-(2,2-dimethylbutanoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)acetate | 1314081-57-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-methyl 2-(2-(2,2-dimethylbutanoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)acetate
• 英文别名: (S)-5-(1-(2-chlorophenyl)-2-methoxy-2-oxoethyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl 2,2-dimethylbutanoate；(S)-methyl 2-(2-(2,2-dimethylbutanoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate；[5-[(1S)-1-(2-chlorophenyl)-2-methoxy-2-oxoethyl]-6,7-dihydro-4H-thieno[3,2-c]pyridin-2-yl] 2,2-dimethylbutanoate
• CAS: 1314081-57-6
• 化学式: C₂₂H₂₆ClNO₄S
• 分子量: 435.972
• InChiKey: QMXFQSJTYAEYQD-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  84.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-methyl 2-(2-(2,2-dimethylbutanoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)acetate 在 盐酸 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 0.08h， 以88%的产率得到(S)-methyl 2-(2-(2,2-dimethylbutanoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate hydrochloride
  参考文献：
  名称：

  OPTICALLY ACTIVE 2-HYDROXY TETRAHYDROTHIENOPYRIDINE DERIVATIVES, PREPARATION METHOD AND USE IN MANUFACTURE OF MEDICAMENT THEREOF

  摘要：

  光学活性的2-羟基四氢噻吡啶衍生物，其化学式如下所示，并且还公开了其药用可接受的盐、制备方法以及在制备药物中的用途。药效实验结果表明，化学式I的这些化合物对抑制血小板聚集是有用的。药代动力学实验结果表明，化学式I的这些化合物在体内可以转化为药理活性代谢物，因此对于抑制血小板聚集是有用的。因此，这些化合物对于制备用于预防或治疗与血栓形成和栓塞相关的疾病的药物是有用的。

  公开号：

  US20130165476A1
• 作为产物：
  描述：

  2-氯扁桃酸甲酯 在 4-二甲氨基吡啶 、 potassium hydrogencarbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 34.17h， 生成 (S)-methyl 2-(2-(2,2-dimethylbutanoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)acetate
  参考文献：
  名称：

  Overcoming Clopidogrel Resistance: Discovery of Vicagrel as a Highly Potent and Orally Bioavailable Antiplatelet Agent

  摘要：

  A series of optically active 2-hydroxytetrahydrothienopyridine derivatives were designed and synthesized as prodrugs of clopidogrel thiolactone in order to overcome clopidogrel resistance. The final compounds were evaluated for their inhibitory effect on ADP-induced platelet aggregation in rats. Compound 9a was selected for further in vitro and in vivo metabolism studies, since its potency was comparable to that of prasugrel and was much higher than that of clopidogrel. Preliminary pharmacokinetic study results showed that the bioavailability of clopidogrel thiolactone generated from 9a was 6-fold higher than that generated from clopidogrel, implying a much lower clinically effective dose for 9a in comparison with clopidogrel. In summary, 9a (vicagrel) holds great promise as a more potent and a safer antiplatelet agent that might have the following advantages over clopidogrel: (1) no drug resistance for CYP2C19 poor metabolizers; (2) lower dose-related toxicity due to a much lower effective dose; (3) faster onset of action.

  DOI：

  10.1021/jm300038c

文献信息

• Optically active 2-hydroxy tetrahydrothienopyridine derivatives, preparation method and use in manufacture of medicament thereof
  申请人：Sun Hongbin

  公开号：US08772489B2

  公开（公告）日：2014-07-08

  Optically active 2-hydroxytetrahydrothienopyridine derivatives represented by Formula I and pharmaceutically acceptable salts, preparation method and use in the manufacture of a medicament thereof are disclosed. The pharmacodynamic experiment results show that the present compounds of Formula I are useful for inhibiting platelet aggregation. The pharmacokinetic experiment results show that the present compound of Formula I can be converted in vivo into pharmacologically active metabolites and are therefore useful for inhibiting platelet aggregation. Therefore, the present compounds are useful for the manufacture of a medicament for preventing or treating thrombosis and embolism related diseases.

  本发明公开了由式I所表示的光学活性2-羟基四氢噻吩吡啶衍生物及其药学上可接受的盐、制备方法和用于制备药物的用途。药效学实验结果表明，式I的化合物对于抑制血小板聚集是有用的。药代动力学实验结果表明，式I的化合物能在体内转化为药理活性代谢物，因此对于抑制血小板聚集是有用的。因此，本发明的化合物对于制备预防或治疗与血栓形成和栓塞有关的疾病的药物是有用的。
• US8772489B2
  申请人：——

  公开号：US8772489B2

  公开（公告）日：2014-07-08
• [EN] OPTICALLY ACTIVE 2-HYDROXY TETRAHYDROTHIENOPYRIDINE DERIVATIVES, PREPARATION METHOD AND USE IN MANUFACTURE OF MEDICAMENT THEREOF<br/>[FR] DÉRIVÉS DE 2-HYDROXYTÉTRAHYDROTHIÉNOPYRIDINE OPTIQUEMENT ACTIFS, LEUR PROCÉDÉ DE PRÉPARATION ET UTILISATION DANS FABRICATION DE MÉDICAMENT
  申请人：JIANGSU VCARE PHARMATECH CO LTD

  公开号：WO2011095049A1

  公开（公告）日：2011-08-11

  Optically active 2-hydroxy tetrahydrothienopyridine derivatives represented by formula I and pharmaceutically acceptable salts, preparation method and use in the manufacture of a medicament thereof are disclosed. The pharmacodynamic experiment result shows that the present compounds of formula I are useful for inhibiting platelet aggregation; the pharmacokinetic experiment result shows that the present compounds of formula I can convert in vivo into pharmacological metabolites and are therefore useful for inhibiting platelet aggregation. Therefore, the present compounds can be useful for the manufacture of a medicament of preventing or treating thrombosis and embolism relevant diseases.
• OPTICALLY ACTIVE 2-HYDROXY TETRAHYDROTHIENOPYRIDINE DERIVATIVES, PREPARATION METHOD AND USE IN MANUFACTURE OF MEDICAMENT THEREOF
  申请人：Jiangsu Vcare Pharmatech Co., Ltd

  公开号：EP2532668B1

  公开（公告）日：2017-05-24
• Overcoming Clopidogrel Resistance: Discovery of Vicagrel as a Highly Potent and Orally Bioavailable Antiplatelet Agent
  作者：Jiaqi Shan、Boyu Zhang、Yaoqiu Zhu、Bo Jiao、Weiyi Zheng、Xiaowei Qi、Yanchun Gong、Fang Yuan、Fusheng Lv、Hongbin Sun

  DOI：10.1021/jm300038c

  日期：2012.4.12

  A series of optically active 2-hydroxytetrahydrothienopyridine derivatives were designed and synthesized as prodrugs of clopidogrel thiolactone in order to overcome clopidogrel resistance. The final compounds were evaluated for their inhibitory effect on ADP-induced platelet aggregation in rats. Compound 9a was selected for further in vitro and in vivo metabolism studies, since its potency was comparable to that of prasugrel and was much higher than that of clopidogrel. Preliminary pharmacokinetic study results showed that the bioavailability of clopidogrel thiolactone generated from 9a was 6-fold higher than that generated from clopidogrel, implying a much lower clinically effective dose for 9a in comparison with clopidogrel. In summary, 9a (vicagrel) holds great promise as a more potent and a safer antiplatelet agent that might have the following advantages over clopidogrel: (1) no drug resistance for CYP2C19 poor metabolizers; (2) lower dose-related toxicity due to a much lower effective dose; (3) faster onset of action.