Synthesis and pharmacological characterization of a series of leukotriene analogues with antagonist and agonist activities

Article abstract of 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 pK(B) values of 6.4 and 5.8, respectively. On guinea pig ileum, the pK(B) 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.