蒎烷-血栓素A2的合成及其生物学特性，一种冠状动脉收缩、血小板聚集和血栓素形成的选择性抑制剂。
Synthesis and biological properties of pinane-thromboxane A2, a selective inhibitor of coronary artery constriction, platelet aggregation, and thromboxane formation.
作者信息
Nicolaou K C, Magolda R L, Smith J B, Aharony D, Smith E F, Lefer A M
出版信息
Proc Natl Acad Sci U S A. 1979 Jun;76(6):2566-70. doi: 10.1073/pnas.76.6.2566.
Abstract
Pinane-thromboxane A2 (PTA2, [1alpha,2 beta(Z),-3 alpha (1E,3R*),5 alpha]-7-(3-(3-hydroxy-1-octenyl)-6,6-dimethylbicyclo[3.1.1]hept-2-yl)-5-heptenoic acid) has been synthesized and tested for biological activity in systems responsive to thromboxane A2, stable prostaglandin endoperoxide (PGH2) analogs, and prostatacyclin (PGI2). At low concentrations, PTA2 inhibited cat coronary artery constriction induced by stable prostaglandin endoperoxide analogs, and it stabilized liver lysosomes. At slightly higher concentrations, it inhibited platelet aggregation. At still higher concentrations, PTA2 inhibited thromboxane synthetase, but it had no effect on prostacyclin synthetase. The analog also had no effect on the inhibition of platelet aggregation by PGI2 or prostaglandin D2. It is suggested that PTA2 has a suitable biochemical profile for use as an antithrombotic agent.
摘要
蒎烷 - 血栓素A2（PTA2，[1α,2β(Z),-3α(1E,3R*),5α]-7-(3-(3 - 羟基 - 1 - 辛烯基)-6,6 - 二甲基双环[3.1.1]庚 - 2 - 基)-5 - 庚烯酸）已被合成，并在对血栓素A2、稳定的前列腺素内过氧化物（PGH2）类似物和前列环素（PGI2）有反应的系统中测试了其生物活性。在低浓度下，PTA2抑制由稳定的前列腺素内过氧化物类似物诱导的猫冠状动脉收缩，并能稳定肝溶酶体。在稍高浓度下，它抑制血小板聚集。在更高浓度下，PTA2抑制血栓素合成酶，但对前列环素合成酶没有影响。该类似物对PGI2或前列腺素D2抑制血小板聚集也没有影响。有人认为PTA2具有适合用作抗血栓药物的生化特性。
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