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 inhibitor s. In this paper their synthesis and in vitro PAF-antagonistic effect are described. Introduction in position 2 of a long aliphatic chain be aring 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 c orrelation can be established between global lipophilicity and the ant i-aggregant activity. Structural requirements for a potent activity ar e discussed and are consistent with the hypothesis we have proposed fo r the PAF receptor considered as a multipolarized structure with alter nants of electropositive, electronegative and hydrophobic areas.