Document Report Card

ID: ALA1123967

Journal: J Med Chem

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

Authors: Nakai H, Konno M, Kosuge S, Sakuyama S, Toda M, Arai Y, Obata T, Katsube N, Miyamoto T, Okegawa T.

Abstract: (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-RS-411 (19h) were the most potent and orally active antagonists, respectively. Structure-activity relationships are discussed.

CiteXplore: 3336036

DOI: 10.1021/jm00396a013