[PAF-antagonists with phospholipid structure. 2. Phospholipids with heteroarene head groups and variations of the phosphorus-nitrogen distance; synthesis, characterization and structure-activity relationships].
A series of 27 PAF-analogues with heteroarene head groups and variation of the P-N-distance on the C-3-position of the backbone were synthesized, and the PAF-antagonistic activity on human blood platelets in vitro was evaluated. Investigation of structure-activity relationships revealed that PAF-antagonistic activity is strongly influenced by the 4-(Dimethylamino)-pyridine as polar head base and the distance between phosphate group and onium center. Maximal activity was observed with a chain length of 3 or 4 methylene groups. Among the compounds tested, 1-O-Hexadecyl-2-n-propylpropan-1,3-diol-3-phosphoric acid-4'-[4-(dimethylamino)pyridinium]butylester was the most effective inhibitor in the in vitro assay (KB = 0.3 mumol/l).
Kertscher
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Sektion Biowissenschaften, Universität Leipzig.
Ostermann
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D002855:Chromatography, Thin Layer; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009584:Nitrogen / Q000737:chemistry; D010743:Phospholipids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010758:Phosphorus / Q000737:chemistry; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013329:Structure-Activity Relationship
D010743:Phospholipids; D010972:Platelet Activating Factor; D010758:Phosphorus; D009584:Nitrogen
PAF-Antagonisten mit Phospholipidstruktur. 2. Mitteilung: Phospholipide mit Heteroarenkopfgruppen und verlängerter Phosphor-Stickstoff-Distanz; Synthese, Charakterisierung und Struktur-Wirkungs-Vergleich.