STRUCTURE-ACTIVITY-RELATIONSHIPS IN PLATELET-ACTIVATING-FACTOR (PAF) .8. TETRAHYDROFURAN DERIVATIVES AS DUAL PAF ANTAGONISTS AND ACETYLCHOLINESTERASE INHIBITORS - ANTIACETYLCHOLINESTERASE ACTIVITY AND COMPARATIVE SAR

2,5-disubstituted tetrahydrofuran derivatives display a dual functiona lity: they are PAF antagonists and acetylcholinesterase (AChE) inhibit ors. In vitro anti-AChE activity and in vivo trials are presented here in, These compounds are competitive and potent AChE inhibitors, Struct ure-activity relationships are described and compared with PAF-antagon ist results, The presence of an onium group, a suitable distance suppl ied by a chain of 7 or 10 carbon atoms separating the function from th e polar head and an appreciable chain hydrophobicity (4 < Sigma f < 7) are the main features required for a dual activity, The derivatives a re evaluated in a mouse passive avoidance model, Only compounds with b oth activities are able to reverse scopolamine-induced amnesia. In add ition, they display a very weak toxicity.