title: New potent antagonists of leukotrienes C4 and D4. 1. Synthesis and structure-activity relationships.
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.
authors.affiliation: Research Institute, Ono Pharmaceutical Co., Ltd., Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakai
authors.forename: M
authors.initials: M
authors.lastname: Konno
authors.forename: S
authors.initials: S
authors.lastname: Kosuge
authors.forename: S
authors.initials: S
authors.lastname: Sakuyama
authors.forename: M
authors.initials: M
authors.lastname: Toda
authors.forename: Y
authors.initials: Y
authors.lastname: Arai
authors.forename: T
authors.initials: T
authors.lastname: Obata
authors.forename: N
authors.initials: N
authors.lastname: Katsube
authors.forename: T
authors.initials: T
authors.lastname: Miyamoto
authors.forename: T
authors.initials: T
authors.lastname: Okegawa
mesh_terms: D000818:Animals; D001993:Bronchodilator Agents / Q000138:chemical synthesis*; D002934:Cinnamates / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009119:Muscle Contraction / Q000187:drug effects*; D013189:SRS-A / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D062367:ortho-Aminobenzoates / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D001993:Bronchodilator Agents; D002934:Cinnamates; D013189:SRS-A; D062367:ortho-Aminobenzoates