Ghali N I, Kattelman E J, Hung S C, Schnorf K E, Le Breton G C, Venton D L
Prostaglandins. 1984 Jun;27(6):865-76. doi: 10.1016/s0090-6980(84)80006-4.
Because of its highly unstable nature, TXA2, produced by platelet metabolism of arachidonic acid, does not lend itself to use as a receptor probe for its own receptor. As such, the stable TXA2/PGH2 antagonist, trans-13-azaprostanoic acid (trans-13-APA, 12b), was prepared as the [17, 18 3H] derivative [( 3H] trans-13-APA, 12c) to study this receptor and to better evaluate the mechanism of action of these azaprostanoids. Tritiated trans-13-APA, 12c, was prepared in nearly theoretical specific activity (57 Ci/mmole) from (17Z)-trans-13-azaprost-17-enoic acid (11b) by catalytic tritiation. The unsaturated 11b was prepared by condensation of cis-7-amino-3-heptene (8) with 2-(6-carboxyhexyl) cyclopentanone (9), NaBH4 reduction, chromatography, and hydrolysis of the trans isomer so isolated. The olefins 11a and b were also of biochemical interest because of the unsaturation in the lower side chain. The presence of similar unsaturation in PGH3(4) and TXA3 (3) renders these prostaglandins inactive as proaggregatory agents. Evaluation of the antiaggregatory activity of 11a and b indicated it to be about the same potency in inhibiting human platelet aggregation as the parent cis and trans-13-APAs, suggesting that introduction of a double bond at the 17 position in platelet prostaglandin antagonists is unlikely to result in enhanced antiplatelet activity.
由于其高度不稳定的性质，由花生四烯酸的血小板代谢产生的血栓素A2（TXA2）不适合用作其自身受体的受体探针。因此，制备了稳定的TXA2/前列环素H2（PGH2）拮抗剂反式-13-氮杂前列腺素酸（反式-13-APA，12b）作为[17,18-3H]衍生物（[3H]反式-13-APA，12c），以研究该受体并更好地评估这些氮杂前列腺素的作用机制。通过催化氚化从（17Z）-反式-13-氮杂前列腺-17-烯酸（11b）制备了具有几乎理论比活性（57 Ci/mmol）的氚化反式-13-APA，12c。不饱和的11b通过顺式-7-氨基-3-庚烯（8）与2-（6-羧基己基）环戊酮（9）缩合、硼氢化钠还原、色谱法以及对如此分离得到的反式异构体进行水解来制备。烯烃11a和b由于其侧链下部的不饱和性也具有生化意义。PGH3（4）和TXA3（3）中类似不饱和性的存在使这些前列腺素作为促聚集剂无活性。对11a和b的抗聚集活性评估表明，其抑制人血小板聚集的效力与母体顺式和反式-13-APA大致相同，这表明在血小板前列腺素拮抗剂的17位引入双键不太可能导致增强的抗血小板活性。
