Disubstituted tetrahydrofurans and dioxolanes and PAF antagonists.
A new series of disubstituted tetrahydrofuran and dioxolane derivatives were prepared and evaluated for their PAF antagonist activity in the PAF-induced in vitro platelet-aggregation and in vivo hypotension tests. Several of these compounds exhibited more potent activity than the structurally related 2-[N-acetyl-N-[[[[2-methoxy-3-[(octadecylcarbamoyl) oxy]propoxy]carbonyl]amino]methyl]-1-ethylpyridinium chloride (CV-6209, 3) in the in vitro assay, whereas all showed less potency in the in vivo test. The role of both the substituent nature and the placement and number of oxygen atoms in the ring are discussed. A quantitative SAR study carried out on these nuclei.
Bartrolí
J
J
Chemistry Laboratories, J. Uriach & Cía.S.A., Barcelona, Spain.
Carceller
E
E
Merlos
M
M
García-Rafanell
J
J
Forn
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004148:Dioxolanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015394:Molecular Structure; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D004148:Dioxolanes; D005663:Furans; D007202:Indicators and Reagents; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; C018674:tetrahydrofuran