Grue-Sørensen G, Nielsen I M, Nielsen C K
Chemical Research Department, Leo Pharmaceutical Products, Ballerup, Denmark.
J Med Chem. 1988 Jun;31(6):1174-8. doi: 10.1021/jm00401a017.
Two new achiral platelet activating factor (PAF) antagonists, N-[5-[[2-methylene-3- [[(octadecylamino)carbonyl]oxy]propoxy]carbonyl]pentyl]pyridinium bromide and 3-[6-[[2-methylene-3- [[(octadecylamino)carbonyl]oxy]propoxy]carbonyl]hexyl]thiazolium bromide were synthesized from 2-methylenepropane-1,3-diol. Platelet aggregation in platelet-rich plasma from rabbits, induced by racemic C16-PAF, was competitively antagonized by 9 or 10. At concentrations less than or equal to 10(-4) M, neither compound 9 nor compound 10 caused platelet aggregation, nor did they inhibit platelet aggregation induced by collagen or adenosine diphosphate. Bronchoconstriction in the guinea pig and hypotension in the rat, induced by racemic C16-PAF, were also effectively antagonized by 9 and 10. Both appear to be more potent as PAF antagonists than Takeda's CV-3988.
由2-亚甲基丙烷-1,3-二醇合成了两种新的非手性血小板活化因子（PAF）拮抗剂，即溴化N-[5-[[2-亚甲基-3-[[(十八烷基氨基)羰基]氧基]丙氧基]羰基]戊基]吡啶鎓和溴化3-[6-[[2-亚甲基-3-[[(十八烷基氨基)羰基]氧基]丙氧基]羰基]己基]噻唑鎓。外消旋C16-PAF诱导的兔富血小板血浆中的血小板聚集受到9或10的竞争性拮抗。在浓度小于或等于10^(-4) M时，化合物9和化合物10均未引起血小板聚集，也未抑制胶原蛋白或二磷酸腺苷诱导的血小板聚集。外消旋C16-PAF诱导的豚鼠支气管收缩和大鼠低血压也被9和10有效拮抗。两者作为PAF拮抗剂似乎比武田公司的CV-3988更有效。
