Structure-activity relationships in platelet-activating factor (PAF antagonists). 6. Synthesis and in vitro antagonistic activities of 2-substituted 5-oxotetrahydrofurans.
The synthesis of 2,5-disubstituted tetrahedrofuran compounds as potential in vitro PAF antagonists is described. Results demonstrate that the structural requirements for potent PAF antagonist activity are: a moderate lipophilic group or a trimethoxyphenyl group in position-5, and a long aliphatic chain terminated by a cationic polar head in position-2. The cis-trans configuration does not induce any difference in biological activity. Some conformational features of the putative PAF receptor are proposed in light of the present findings.
Favre
E
E
Laboratoire de Pharmacochimie Moléculaire, Unité de Recherches Chimie et Pharmacologie, Université Paris, France.
Heymans
F
F
Redeuilh
C
C
Batt
J P
JP
Massicot
F
F
Blavet
N
N
Braquet
P
P
Godfroid
J J
JJ
D000818:Animals; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D005663:Furans; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; C018674:tetrahydrofuran