SYNTHESIS AND BIOLOGICAL PROPERTIES OF PINANE-THROMBOXANE-A2, A SELECTIVE INHIBITOR OF CORONARY-ARTERY CONSTRICTION, PLATELET-AGGREGATION, AND THROMBOXANE FORMATION
SYNTHESIS AND BIOLOGICAL PROPERTIES OF PINANE-THROMBOXANE-A2, A SELECTIVE INHIBITOR OF CORONARY-ARTERY CONSTRICTION, PLATELET-AGGREGATION, AND THROMBOXANE FORMATION
复制标题
DOI：
10.1073/pnas.76.6.2566
复制
发表时间：
1979-01-01
影响因子：
11.1
通讯作者：
LEFER, AM
中科院分区：
文献类型：
--
作者：
NICOLAOU, KC;MAGOLDA, RL;LEFER, AM
合成了平烷-血栓素A2(PtA2，[1，α，2，β(Z)，-3.alpha.(1E，3R)，5.alpha.]-7-{3-(3-hydroxy-1-octenyl)-6，6-dimethylbicyclo[3.1.1]hept-2-yl}-5-heptenoic酸])，并在对血栓素A2、稳定的前列腺素过氧化物(PgH_2)类似物和前列环素(PGI_2)反应的系统中测试了生物活性。在低浓度时，PTA2可抑制稳定的前列腺素内源性过氧化类似物所致的猫冠状动脉收缩，并稳定肝脏溶酶体。当浓度稍高时，它会抑制血小板聚集。在更高浓度时，PTA2抑制血栓素合成酶，但不影响前列环素合成酶。该类似物对前列腺素D2或前列腺素D2抑制血小板聚集无明显作用。显然，PTA2具有合适的生化特性，可用作抗血栓药物。
Pinane-thromboxane A2 (PTA2, [1.alpha.,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) was synthesized and tested for biological activity in systems responsive to thromboxane A2, stable prostaglandin endoperoxide (PGH2) analogs and prostacyclin (PGI2). At low concentrations PTA2 inhibited cat coronary artery constriction induced by stable prostaglandin endoperoxide analogs and stabilized liver lysosomes. At slightly higher concentrations it inhibited platelet aggregation. At still higher concentrations PTA2 inhibited thromboxane synthetase but did not effect prostacyclin synthetase. The analog had no effect on the inhibition of platelet aggregation by PGI2 or prostaglandin D2. Apparently, PTA2 has a suitable biochemical profile for use as an antithrombotic agent.