Venton D L, Enke S E, Le Breton G C
J Med Chem. 1979 Jul;22(7):824-30. doi: 10.1021/jm00193a014.
A series of 13-azaprostanoic acids (4a-h) and a 15-azaprostanoic acid (11a) have been prepared. Synthesis of the 15-aza derivative is based on a novel transformation of a ketone to an N-substituted ethylenamine using a formylmethylimino phosphate derivative. Several of the azaprostanoic acid derivatives were found to be potent inhibitors of platelet aggregation induced by arachidonic acid, whereas no effect was observed on ADP-induced primary aggregation, indicating blockade of the platelet arachidonic acid cascade. The compounds do not inhibit bovine cyclooxygenase activity and are postulated as acting beyond the synthesis of the prostaglandin endoperoxides. The inhibitory effect of the 13-aza series is highly sensitive to both stereochemistry and length of the amino side chain. Any deviation from the natural prostaglandin skeletal arrangement results in decreased biological activity.
已制备出一系列13-氮杂前列腺酸（4a - h）和一种15-氮杂前列腺酸（11a）。15-氮杂衍生物的合成基于一种使用甲酰甲基亚氨基磷酸酯衍生物将酮转化为N-取代乙二胺的新型转化方法。发现几种氮杂前列腺酸衍生物是花生四烯酸诱导的血小板聚集的有效抑制剂，而对ADP诱导的初级聚集没有观察到影响，表明阻断了血小板花生四烯酸级联反应。这些化合物不抑制牛环氧化酶活性，推测其作用于前列腺素内过氧化物合成之后。13-氮杂系列的抑制作用对立体化学和氨基侧链的长度都高度敏感。与天然前列腺素骨架排列的任何偏差都会导致生物活性降低。
