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COMPARATIVE STUDIES OF ANTIPLATELET ACTIVITY OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS AND NEW PYRAZINE CH AND NH ACIDS

机译:非甾体类抗炎药与新吡嗪CH和NH酸的抗血小板活性比较研究

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摘要

Nine known nonsteroidal antiinflammatory drugs (NSAID) and three new pyrazine derivatives possessing an active methylene moiety (pyrazine CH/NH-acids) were tested with regards to their in vitro and in vivo antiplatelet activity. Concentrations of the agent were determined which caused 25% and 50% inhibition of aggregation of human blood platelets induced by fixed concentrations of ADP, collagen and epinephrine. The in vivo test consisted in determination of percent protection of mice from pulmonary microembolism caused by injection of a mixture of collagen and epinephrine. The in vitro antiaggregatory activity of the collagen-induced aggregation CH/NH-acids appeared highly potent antithrombotic agents in vivo. Activity of NSAID expressed as percent protection against lung thromboembolism in the mouse was demonstrated to depend quantitatively on acid properties of the agents. The new chemical class of pharmacologically active agents, pyrazine CH/NH-acids, offers an original pharmacophore which is distinctive from the carboxylic or enolic functionalities typical for the established NSAID, and as such, may be devoid of some disadvantages of known antiplatelet drugs. [References: 24]
机译:测试了九种已知的非甾体抗炎药(NSAID)和三种具有活性亚甲基部分的新吡嗪衍生物(吡嗪CH / NH-酸)的体外和体内抗血小板活性。确定了引起固定浓度的ADP,胶原蛋白和肾上腺素诱导的人血小板聚集的25%和50%抑制的药物浓度。体内测试包括确定对小鼠注射胶原蛋白和肾上腺素混合物引起的肺微栓塞的保护百分比。胶原蛋白诱导的聚集CH / NH-酸的体外抗聚集活性在体内表现出高度有效的抗血栓形成剂。 NSAID的活性表示为对小鼠肺血栓栓塞的防护百分率,其活性在数量上取决于试剂的酸性。新型化学药理活性剂吡嗪CH / NH-酸提供了原始药效基团,该药基团不同于已建立的NSAID的典型羧基或烯醇官能团,因此可以避免已知抗血小板药的某些缺点。 [参考:24]

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