title: Structure-activity relationships in platelet-activating factor (PAF). 7. Tetrahydrofuran derivatives as dual PAF antagonists and acetylcholinesterase inhibitors. Synthesis and PAF-antagonistic activity.
abstract: 2,5-Disubstituted tetrahydrofuran derivatives present a dual activity: they are effective PAF antagonists and acetylcholinesterase inhibitors. In this paper their synthesis and in vitro PAF-antagonistic effect are described. Introduction in position 2 of a long aliphatic chain bearing a carbamate group and a pyridinium moiety appears to be required for potent platelet aggregation inhibition. Substitution in position 5, or cis-trans isomerism do not induce any increase in activity. No correlation can be established between global lipophilicity and the anti-aggregant activity. Structural requirements for a potent activity are discussed and are consistent with the hypothesis we have proposed for the PAF receptor considered as a multipolarized structure with alternants of electropositive, electronegative and hydrophobic areas.
authors.affiliation: Université Paris 7-Denis Diderot, France.
authors.forename: L
authors.initials: L
authors.lastname: Le Texier
authors.forename: E
authors.initials: E
authors.lastname: Favre
authors.forename: C
authors.initials: C
authors.lastname: Redeuilh
authors.forename: N
authors.initials: N
authors.lastname: Blavet
authors.forename: T
authors.initials: T
authors.lastname: Bellahsene
authors.forename: G
authors.initials: G
authors.lastname: Dive
authors.forename: E
authors.initials: E
authors.lastname: Pirotzky
authors.forename: J J
authors.initials: JJ
authors.lastname: Godfroid
mesh_terms: D002219:Carbamates / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004952:Esters / Q000494:pharmacology; D005663:Furans / Q000737:chemistry; D007536:Isomerism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D002219:Carbamates; D002800:Cholinesterase Inhibitors; D004952:Esters; D005663:Furans; D010972:Platelet Activating Factor; C018674:tetrahydrofuran