[PAF-antagonists with phospholipid structure. 3. Phospholipids with heterocyclane head groups and variations of the phosphorus-nitrogen distance; synthesis, characterization and structure-activity relationship].
A series of 13 PAF-analogues with heterocyclane head groups and variation of the P-N-distance on the C-3-position of the backbone were synthesized. The proaggregatory and inhibitory potencies on rabbit and human blood platelets in vitro was evaluated. Investigations of structure-activity relationship revealed that the PAF-inhibitory potency is strongly influenced by the distance between phosphate and onium center and the structure of the heterocyclane. Derivatives with a P-N-distance of 4 or more methylene groups emerged effective inhibitors. The best activity was observed by chinuclidine- and N-methylpiperidine analogues with a chain length of 6 methylene groups (KB = 1.1 to 2.3 mumol/l).
Kertscher
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Sektion Biowissenschaften, Universität Leipzig.
Ostermann
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D000818:Animals; D002855:Chromatography, Thin Layer; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008968:Molecular Conformation; D010743:Phospholipids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013329:Structure-Activity Relationship
D006571:Heterocyclic Compounds; D010743:Phospholipids; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors
PAF-Antagonisten mit Phospholipidstruktur. 3. Mitteilung: Phospholipide mit Heterocyclankopfgruppen und veränderter Phosphor-Stick-stoff-Distanz; Synthese, Charakterisierung und Struktur-Wirkungsvergleich.