[PAF-antagonists with a phospholipid structure. 5. Propanediol phospholipids with various substituted pyridinium and quinuclidinium head groups and variations of the phosphorus-nitrogen distance;synthesis, characterization and structure activity relationship].
A series of 10 PAF-analogues, structurally modified in position C-2 (n-propyl) and position C-3 (polar head group) were synthesized, and the PAF-inhibitory potencies was evaluated using PAF-induced aggregation of human blood platelets in vitro. Structure-activity relationships revealed, that the PAF-inhibitory activity is strongly influenced by the distance between phosphate and onium center and the structure of the substituted heterocyclus. The best activity was observed by 3,5-dimethylpyridinium- and 4-ethylpyridinium derivative with a P-N-distance of 6 methylene groups (IC50 = 1.9 x 10(-6) mol/l and 2.7 x 10(-6) mol/l).
Kertscher
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Fachbereich Biowissenschaften, Universität Leipzig, Berlin.
Schwabe
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D001792:Blood Platelets / Q000187:drug effects; D002855:Chromatography, Thin Layer; D006801:Humans; D066298:In Vitro Techniques; D010743:Phospholipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D011409:Propylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011812:Quinuclidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013329:Structure-Activity Relationship
D010743:Phospholipids; D010972:Platelet Activating Factor; D011409:Propylene Glycols; D011726:Pyridinium Compounds; D011812:Quinuclidines