New potent antagonists of leukotrienes C4 and D4. 1. Synthesis and structure-activity relationships

Article abstract of DOI:10.1021/jm00396a013

(p-Amylcinnamoyl)anthranilic acid (3a) had moderate antagonist activities against LTD₄-induced smooth muscle contraction on guinea pig ileum and LTC₄-induced bronchoconstriction in anesthetized guinea pigs. Modifications were made in the hydrophobic part (cinnamoyl moiety) and the hydrophilic part (anthranilate moiety) of 3a. A series of 8-(benzoylamino)-2-tetrazol-5-yl-1,4-benzodioxans and 8-(benzoylamino)-2-tetrazol-5-yl-4-oxo-4H-1-benzopyrans were revealed to be potent antagonists of leukotrienes C₄ and D₄. Among both series, ONO-RS-347 (18k) and ONO-RS411 (19h) were the most potent and orally active antagonists, respectively. Structure-activity relationships are discussed.