（±）-反式-2-（3-甲氧基-5-甲基磺酰基-4-丙氧基苯基）-5-（3,4,5-三甲氧基苯基）四氢呋喃（L-659,989），一种新型强效血小板活化因子受体拮抗剂。
(+/-)-trans-2-(3-Methoxy-5-methylsulfonyl-4-propoxyphenyl)-5-(3,4,5- trimethoxyphenyl)tetrahydrofuran (L-659,989), a novel, potent PAF receptor antagonist.
作者信息
Ponpipom M M, Hwang S B, Doebber T W, Acton J J, Alberts A W, Biftu T, Brooker D R, Bugianesi R L, Chabala J C, Gamble N L
机构信息
Merck Sharp & Dohme Research Laboratories, Rahway, NJ 07065.
出版信息
Biochem Biophys Res Commun. 1988 Feb 15;150(3):1213-20. doi: 10.1016/0006-291x(88)90758-9.
The title compound, L-659,989, is a highly potent, competitive, and selective antagonist of the binding of [3H]PAF to its receptors in platelet membranes from rabbits and humans. It exhibits equilibrium inhibition constants for PAF binding of 1.1 nM (rabbit) to 9.0 nM (human), values that are at least 1-2 orders of magnitude lower than those of other PAF antagonists tested. L-659,989 potently inhibits PAF-induced aggregation of rabbit platelets and degranulation of rat (ED50 4.5 nM) and human (ED50 10 nM) neutrophils. L-659,989 inhibits PAF-induced extravasation and lysosomal enzyme release in rats, and is active orally in female rats (ED50 0.2 mg/kg) with an extraordinary oral duration of action of 12 to 16 hours at 1.0 mg/kg p.o.
标题化合物L-659,989是一种高效、竞争性且具有选择性的拮抗剂，可抑制[3H]PAF与兔和人血小板膜中其受体的结合。它对PAF结合的平衡抑制常数为1.1 nM（兔）至9.0 nM（人），该值比所测试的其他PAF拮抗剂至少低1至2个数量级。L-659,989有效抑制PAF诱导的兔血小板聚集以及大鼠（ED50 4.5 nM）和人（ED50 10 nM）中性粒细胞的脱颗粒。L-659,989抑制PAF诱导的大鼠血管外渗和溶酶体酶释放，并且在雌性大鼠中口服活性良好（ED50 0.2 mg/kg），口服1.0 mg/kg时具有12至16小时的超长作用持续时间。
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