含有取代哌嗪及哌啶结构的噻吩并吡啶类化合物的合成及活性研究

成碟 ;刘颖 ;刘登科 ;刘默 ;徐为人 ;刘昌孝

中国药学杂志 ›› 2009, Vol. 44 ›› Issue (22) : 1752-1754.

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中国药学杂志
PDF(1714 KB)
中国药学杂志 ›› 2009, Vol. 44 ›› Issue (22) : 1752-1754.
论文

含有取代哌嗪及哌啶结构的噻吩并吡啶类化合物的合成及活性研究

  • 成碟 1a ,1b,2 ，刘颖 1b ，刘登科 1b ，刘默 1b ，徐为人 1b ，刘昌孝 1a *
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Synthesis and Activity Evaluation of Some Novel Derivatives of 4, 5, 6, 7-Tetrahydrothieno [3, 2-c]-Pyridine Containing Substituted Piperazine or Piperidine

  • CHENG Die 1a ,1b,2 ， LIU Ying1b ， LIU Deng-ke1b ， LIU Mo1b ， XU Wei-ren1b ， LIU Chang-xiao 1a *
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摘要

目的 设计合成一系列新型的含取代哌嗪及哌啶的噻吩并吡啶类衍生物，并对其体内抗血小板聚集活性进行了初步评价。 方法 从噻吩并吡啶 ( 1 ) 出发，与氯乙酰氯连接得到关键中间体（ 2 ），再与一系列取代哌嗪及哌啶连接得到目标化合物（ 3-19 ）。 结果 得到 17 个新化合物，所有化合物结构都经过 1 H NMR 及质谱确证。这些化合物都进行了大鼠体内抑制血小板聚集活性测试。其中化合物 10-14 具有较高活性。 结论 该类噻吩并吡啶衍生物有可能成为新型结构的具有抗血小板聚集活性的先导化合物，值得进一步研究。

Abstract

OBJECTIVE To design and synthesize a novel series of 4, 5, 6, 7-tetrahydrothieno [3,2-c] pyridine containing substituted piperazine or piperidine derivatives and to test their in vivo anti-platelet aggregation activity in the rat. METHODS Key intermediate 2 was synthesized by connecting compound 1 with chloroacetyl chloride. Title compounds 3-19 were produced by connecting intermediate 2 with a series of substituted piperazine or piperidine. RESULTS 17 novel compounds were synthesized and structurally characterized by 1H NMR and MS. Their in vivo anti-platelet aggregation activities were evaluated in the rat. Compounds 10-14 exhibited more potent inhibitory activity than other compounds synthesized. CONCLUSION These thienopyridine derivatives showed a certain anti-platelet aggregation activity, and were worth further developing as promising lead compounds.

关键词

噻吩并吡啶 / 抗血小板聚集活性 / P2Y12 受体

Key words

thienopyridines / anti-platelet aggregation activities / P2Y12 receptors

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成碟 ;刘颖 ;刘登科 ;刘默 ;徐为人 ;刘昌孝 . 含有取代哌嗪及哌啶结构的噻吩并吡啶类化合物的合成及活性研究[J]. 中国药学杂志, 2009, 44(22): 1752-1754
CHENG Die;LIU Ying;LIU Deng-ke;LIU Mo;XU Wei-ren;LIU Chng-xio . Synthesis and Activity Evaluation of Some Novel Derivatives of 4, 5, 6, 7-Tetrahydrothieno [3, 2-c]-Pyridine Containing Substituted Piperazine or Piperidine[J]. Chinese Pharmaceutical Journal, 2009, 44(22): 1752-1754

参考文献


[1] DUPIN J P ， GRYGLEWSKI R J ， GRAVIER D ， et al . Synthesis and thrombolytic activity of new thienopyrimidinone derivatives[J]. J Physiol Pharmacol ， 2002 ， 53 (4) : 625-634.
[2] STOREY R F. Biology and pharmacology of the platelet P2Y12 receptor[J]. Curr Pharm Des ， 2006 ， 12 (10) :1255-1259.
[3] PANAK E ， MAFFRAND J P ， PICARD-FRAIRE C ， et al . Ticlopidine: a promise for the prevention and treatment of thrombosis and its complications[J]. Haemostasis ， 1983 ， 13 (suppl 1): 1-54.
[4] COUKELL A J ， MARKHAM A. Clopidogrel[J]. Drugs ， 1997 ， 54 (5): 745-750.
[5] SUGIDACHI A ， ASAI F ， YONEDA K ， et al . Antiplatelet action of R-99224 ， an active metabolite of a novel thienopyridine-type Gi-linked P2T antagonist ， CS-747[J]. Br J Pharmacol ， 2001 ， 132 (1 ): 47-54.
[6] HASHIMOTO M ， SUGIDACHI A ， ISOBE T ， et al . The influence of P2Y12 receptor deficiency on the platelet inhibitory activities of prasugrel in a mouse model: Evidence for specific inhibition of P2Y12 receptors by prasugrel[J]. Biochem Pharmacol ， 2007 ， 74 (7 ): 1003-1009.
[7] LODEWIJK E ， KHATRI H N. 2-(2-Nitrovinyl)thiophene reduction and synthesis of thieno (3,2-c)pyridine derivatives. EP0342118[P]. 1989-11-15 .
（ 收稿日期 ： 2008-12-20 ）

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