(S)-methyl 2-(2-acetoxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-phenylacetate | 1314081-70-3

• 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-acetoxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-phenylacetate
• 英文别名: methyl (2S)-2-(2-acetyloxy-6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-2-phenylacetate
• CAS: 1314081-70-3
• 化学式: C₁₈H₁₉NO₄S
• 分子量: 345.419
• InChiKey: ADEWDQXXGFWEQF-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  84.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  methyl 2-(2-fluorophenyl)-2-hydroxyacetate 在 4-二甲氨基吡啶 、 potassium hydrogencarbonate 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 生成 (S)-methyl 2-(2-acetoxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-phenylacetate 、 (R)-methyl 2-(2-acetoxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-phenylacetate
  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：Jiangsu Vcare PharmaTech Co., Ltd.

  公开号：US10000506B2

  公开（公告）日：2018-06-19

  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 代表的具有光学活性的 2-羟基四氢噻吩吡啶衍生物及其药学上可接受的盐、制备方法和在制造药物中的用途。药效学实验结果表明，本发明的式 I 化合物可用于抑制血小板聚集。药代动力学实验结果表明，本发明的式 I 化合物可在体内转化为具有药理活性的代谢物，因此可用于抑制血小板聚集。因此，本化合物可用于制造预防或治疗血栓和栓塞相关疾病的药物。
• 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
• US8772489B2
  申请人：——

  公开号：US8772489B2

  公开（公告）日：2014-07-08
• 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.