氯吡格雷杂质 | 1360923-54-1

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 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
• 中文名称: 氯吡格雷杂质
• 英文名称: (R)-methyl 2-(2-chlorophenyl)-2-(2-oxo-7,7a-dihydrothieno-[3,2-c]pyridin-5(2H,4H,6H)-yl)acetate
• 英文别名: Methyl (2R)-2-(2-chlorophenyl)-2-(2-oxo-2,6,7,7a-tetrahydrothieno[3,2-c]pyridin-5(4H)-yl)acetate；methyl (2R)-2-(2-chlorophenyl)-2-(2-oxo-4,6,7,7a-tetrahydrothieno[3,2-c]pyridin-5-yl)acetate
• CAS: 1360923-54-1
• 化学式: C₁₆H₁₆ClNO₃S
• 分子量: 337.827
• InChiKey: JBSAZVIMJUOBNB-AWKYBWMHSA-N

物化性质

• 沸点：
  488.1±45.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  71.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  氯吡格雷杂质 在 potassium dihydrogenphosphate 、 magnesium(II) chloride hexahydrate 、 葡萄糖 、 水 、 G₆PDH dehydrogenase 、 P₄₅₀ synthase 、 还原型辅酶II(NADPH)四钠盐 、 sodium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 0.5h， 生成 (2Z)-2-[1-[(1R)-1-(2-chlorophenyl)-2-methoxy-2-oxoethyl]-4-sulfanylpiperidin-3-ylidene]acetic acid
  参考文献：
  名称：

  氯吡格雷代谢活性体二硫衍生物、其制备方法及医药用途

  摘要：

  本发明涉及药物化学领域，提供一系列氯吡格雷代谢活性体二硫衍生物、药学上可接受的盐或溶剂化物。这些化合物与氯吡格雷相比，具有更优的代谢特征，能够绕过人体内P450系统，具备很好的成药性。本发明还公开了上述化合物的制备方法及其在医药领域尤其是心脑血管血栓或栓塞性疾病药物领域的用途。

  公开号：

  CN111484446A
• 作为产物：
  描述：

  (S)-2'-氯-α-羟苯基乙酸甲酯 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 30.0h， 生成 氯吡格雷杂质
  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

• 噻吩吡啶类衍生物及其制备方法和用途
  申请人：陕西合成药业股份有限公司

  公开号：CN107304215A

  公开（公告）日：2017-10-31

  本发明属于药物化学技术领域，具体公开了噻吩吡啶类衍生物及其制备方法和用途。本发明通过对噻吩吡啶类化合物的结构进行改造，合成了一系列噻吩吡啶类衍生物新化合物，主要包括和阿司匹林和阿司匹林衍生物进行成酯；化合物进入体内后迅速代谢为有效代谢产物，成功避开了CYP2C19酶的代谢，可直接代谢为活性化合物而发挥药效，从而解决了噻吩吡啶类化合物抵抗问题，有效提高了化合物抗血栓活性，而对出血风险无显著影响，同时这类化合物对肝肾具较理想的保护作用，对其他心血管疾病亦具有潜在的治疗意义。
• 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。
• Mixed disulfide conjugates of thienopyridine compounds and uses thereof
  申请人：The Regents of the University of Michigan

  公开号：US10173980B2

  公开（公告）日：2019-01-08

  This invention is in the field of medicinal chemistry. In particular, the invention relates to mixed disulfide conjugates of thienopyridine compounds, and their use as therapeutics for the treatment, amelioration, and prevention of cardiovascular diseases.

  本发明属于药物化学领域。特别是，本发明涉及噻吩并吡啶化合物的混合二硫化物共轭物，以及它们作为治疗、改善和预防心血管疾病的治疗剂的用途。
• 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
• MIXED DISULFIDE CONJUGATES OF THIENOPYRIDINE COMPOUNDS AND USES THEREOF
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：US20150353492A1

  公开（公告）日：2015-12-10

  This invention is in the field of medicinal chemistry. In particular, the invention relates to mixed disulfide conjugates of thienopyridine compounds, and their use as therapeutics for the treatment, amelioration, and prevention of cardiovascular diseases.