Wissner A, Schaub R E, Sum P E, Kohler C A, Goldstein B M
J Med Chem. 1986 Mar;29(3):328-33. doi: 10.1021/jm00153a005.
Racemic analogues of platelet activating factor (PAF) in which the methylene bridge separating the phosphate and trimethylammonium moieties is altered in length (7a-f) have been prepared. Increasing the length of this bridge results in a progressive decrease in the hypotensive and platelet aggregation responses. Analogues in which the phosphocholine group is substituted with a methyl group (7h and 7i) or a phenyl group (5j) or in which the methylene bridge is replaced with a meta-substituted benzyl group (5k) have been prepared. With respect to both the blood pressure and platelet aggregation responses, 7i and 5k showed little if any changes in potency compared to racemic C16-PAF (1a). While 7h is more potent than 1a with respect to both the hypotensive and platelet aggregation properties, 5j is less potent. Replacement of the phosphate moiety of C18-PAF (1b) with a phosphonate group (7g) leads to decreased activity in both assays. Analogue 11, in which the phosphocholine group has been replaced with a 4-(trimethylammonio)butoxy group, exhibited no detectable hypotensive or platelet aggregating activity. None of the analogues exhibited a separation of the blood pressure and platelet aggregation activities.
已制备了血小板活化因子（PAF）的外消旋类似物，其中分隔磷酸基团和三甲基铵部分的亚甲基桥长度发生了改变（7a - f）。增加该桥的长度会导致降压和血小板聚集反应逐渐降低。已制备了磷酸胆碱基团被甲基（7h和7i）或苯基（5j）取代的类似物，或者亚甲基桥被间位取代苄基取代的类似物（5k）。就血压和血小板聚集反应而言，与外消旋C16 - PAF（1a）相比，7i和5k的活性几乎没有变化。虽然7h在降压和血小板聚集特性方面比1a更有效，但5j的活性较低。用膦酸酯基团取代C18 - PAF（1b）的磷酸基团（7g）会导致两种测定中的活性降低。类似物11中，磷酸胆碱基团被4 - （三甲基铵基）丁氧基取代，未表现出可检测到的降压或血小板聚集活性。这些类似物均未表现出血压和血小板聚集活性的分离。
