(R,S)-methyl 2-(2-acetoxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)acetate | 178688-44-3

• 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: (R,S)-methyl 2-(2-acetoxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)acetate
• 英文别名: methyl 2-(2-acetoxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)acetate；2-acetoxy-5-(α-methoxycarbonyl-2-chlorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c] pyridine；(S)-methyl 2-(2-acetoxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate；methyl 2-(2-acetyloxy-6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-2-(2-chlorophenyl)acetate
• CAS: 178688-44-3
• 化学式: C₁₈H₁₈ClNO₄S
• 分子量: 379.864
• InChiKey: GNHHCBSBCDGWND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  25
• 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：

  2-(2-氯苯基)-2-羟基乙酸甲酯 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 32.0h， 生成 (R,S)-methyl 2-(2-acetoxy-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

• MEDICINAL COMPOSITION
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1319399A1

  公开（公告）日：2003-06-18

  A pharmaceutical composition containing a drug (A), a waxy substance (B), and synthetic aluminum silicate and/or hydrous silicon dioxide (C). The invention provides a granular pharmaceutical composition suitable for providing a pharmaceutical characterized in that adhesion of granules thereof onto a granulation apparatus during granulation is minimized and caking of the granules is suppressed.

  一种药物组合物，包含药物（A）、蜡状物质（B）和合成氧化铝硅和/或水合二氧化硅（C）。该发明提供了一种颗粒状药物组合物，适用于提供一种药物，其特点在于在制粒过程中减少颗粒粘附到制粒设备上，并抑制颗粒结块。
• MEDICINAL COMPOSITIONS
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1161956A1

  公开（公告）日：2001-12-12

  The present invention relates to a granular pharmaceutical composition comprising a drug having a disagreeable taste, a wax and a sugar alcohol; a method for preparing the same; and a pharmaceutical product for oral administration, comprising the granular composition. The product excellently masks a disagreeable taste possessed by a drug and provides good sensation upon oral administration, and therefore is easily ingested by even the elderly, children, and patients suffering dysphagia. Moreover, the product is suitable for administration using tube.

  本发明涉及一种颗粒状药物组合物，该组合物由具有异味的药物、蜡和糖醇组成；一种制备该组合物的方法；以及一种包含该颗粒状组合物的口服药物。该产品能很好地掩盖药物的异味，并在口服时提供良好的感觉，因此即使是老人、儿童和吞咽困难患者也很容易摄入。此外，该产品还适合使用软管给药。
• Tastemasked pharmaceutical compositions
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP2275141A1

  公开（公告）日：2011-01-19

  A granular pharmaceutical composition, comprising (A) a drug having disagreeable taste; (B) one or more of waxy substances selected from the group consisting of hydrogenated castor oil, hydrogenated soybean oil, hydrogenated rape seed oil, hydrogenated cotton seed oil, camauba wax, white bees wax, beef tallow, stearyl alcohol, cetanol, polyethylene glycol, stearic acid, parmitic acid, mono-fatty acid glycerin ester, tri-fatty acid glycerin ester and fatty acid sucrose ester; and (C) erythritol, characterized in that the composition thereof does not cohere in water and has a dosage form of a granule, powder or capsule.

  一种颗粒状药物组合物，包括 (A) 有异味的药物；(B) 一种或多种蜡质物质，选自氢化蓖麻油、氢化大豆油、氢化菜籽油、氢化棉籽油、卡玛巴蜡、白蜂蜡、牛脂、硬脂醇、鲸蜡醇、聚乙二醇、硬脂酸、帕米特酸、单脂肪酸甘油酯、三脂肪酸甘油酯和脂肪酸蔗糖酯组成的组；(C) 赤藓糖醇，其特点是其成分在水中不凝聚，剂型为颗粒、粉末或胶囊。
• 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。
• Medicinal composition
  申请人：——

  公开号：US20040022848A1

  公开（公告）日：2004-02-05

  A pharmaceutical composition containing a drug (A), a waxy substance (B), and synthetic aluminum silicate and/or hydrous silicon dioxide (C). The invention provides a granular pharmaceutical composition suitable for providing a pharmaceutical characterized in that adhesion of granules thereof onto a granulation apparatus during granulation is minimized and caking of the granules is suppressed.

  一种含有药物（A）、蜡状物质（B）和合成硅酸铝和/或水合二氧化硅（C）的药物组合物。本发明提供了一种适用于提供药物的颗粒状药物组合物，其特点是在制粒过程中将颗粒在制粒设备上的附着减至最小，并抑制颗粒的结块。