Structure-activity relationships in platelet-activating factor (PAF). 7. Tetrahydrofuran derivatives as dual PAF antagonists and acetylcholinesterase inhibitors. Synthesis and PAF-antagonistic activity.
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.
Le Texier
L
L
Université Paris 7-Denis Diderot, France.
Favre
E
E
Redeuilh
C
C
Blavet
N
N
Bellahsene
T
T
Dive
G
G
Pirotzky
E
E
Godfroid
J J
JJ
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
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D004952:Esters; D005663:Furans; D010972:Platelet Activating Factor; C018674:tetrahydrofuran