title: A novel class of platelet activating factor (PAF) antagonists. I. Synthesis and structure-activity studies on PAF-sulfonamide isosteres.
abstract: New platelet activating factor (PAF) antagonists, 3 were synthesized by replacing the charged phosphate and trimethylammonium moieties with sulfonamide and heterocyclic quaternary ammonium functionalities, respectively (PAF-sulfonamide isosteres). Darmstoff phosphatidic acid analogues of this class (Darmstoff-sulfonamide isosteres), 6 were also synthesized. The activity of these compounds as PAF antagonists was evaluated from their in vitro inhibitory effect on PAF-induced platelet aggregation in rabbit platelet-rich plasma. Among the compounds tested, some of the 2-methoxypropane derivatives with an octadecylcarbamoyloxy or octadecylcarbamoylthio side chain at the 1-position and a propylsulfonamide function bearing a terminal polar substituent such as a quaternary quinolinium or substituted quinolinium group at the 3-position were found to be the most potent (IC50 = 0.3-0.6 microM).
authors.affiliation: Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tsuri
authors.forename: N
authors.initials: N
authors.lastname: Haga
authors.forename: T
authors.initials: T
authors.lastname: Matsui
authors.forename: S
authors.initials: S
authors.lastname: Kamata
authors.forename: H
authors.initials: H
authors.lastname: Kakushi
authors.forename: K
authors.initials: K
authors.lastname: Uchida
mesh_terms: D000818:Animals; D066298:In Vitro Techniques; D007536:Isomerism; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000737:chemistry; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D013449:Sulfonamides