Bernstein P R, Vacek E P, Adams E J, Snyder D W, Krell R D
Department of Medicinal Chemistry, Stuart Pharmaceuticals, Wilmington, Delaware 19897.
J Med Chem. 1988 Mar;31(3):692-6. doi: 10.1021/jm00398a033.
The synthesis and biological characterization of a series of novel leukotriene antagonists and agonists are reported. All of these compounds are derivatives of (5S,6R,7Z)-5-hydroxy-6-mercapto-9-phenyl-7-nonenoic acid. One of the more potent compounds is (5S,6R,7Z)-6-[[(4-carboxy-2-methoxyphenyl)methyl]thio]-5-hydroxy-9 -(4- heptylphenyl)-7-nonenoic acid (3f). In vitro evaluation of this compound on guinea pig trachea revealed that it is a competitive antagonist of LTD4 and LTE4 with pKB values of 6.4 and 5.8, respectively. On guinea pig ileum, the pKB values obtained for it with LTD4 and E4 were both 7.2. The selectivity of 3f was shown by its lack of effect on carbachol, histamine, and barium chloride concentration-response curves in guinea pig trachea.
报道了一系列新型白三烯拮抗剂和激动剂的合成及生物学特性。所有这些化合物都是(5S,6R,7Z)-5-羟基-6-巯基-9-苯基-7-壬烯酸的衍生物。其中一种活性较强的化合物是(5S,6R,7Z)-6-[[(4-羧基-2-甲氧基苯基)甲基]硫基]-5-羟基-9-(4-庚基苯基)-7-壬烯酸(3f)。对该化合物在豚鼠气管上的体外评估显示，它是LTD4和LTE4的竞争性拮抗剂，其pKB值分别为6.4和5.8。在豚鼠回肠上，它与LTD4和E4的pKB值均为7.2。3f的选择性表现在它对豚鼠气管中卡巴胆碱、组胺和氯化钡浓度-反应曲线无影响。
