[PAF-antagonists with phospholipid structure. 4. Alkylcarbamoylphospholipids with heteroarene and heterocyclase head groups and variation of the P-N-distance; synthesis, characterization and structure-activity relationship].
A series of 11 PAF-analogues, structurally modified in position 1 (alkylcarbamoyloxy), position 2 (n-propyl), and position 3 (polar head group) were synthesized, and the inhibitory potencies on human blood platelets in vitro was evaluated. Investigations of structure-activity relationships revealed, that the PAF antagonist activity is strongly influenced by the chain length of the alkylcarbamoyl residue and the structure of the polar head group. Derivatives with pentadecyl and octadecylcarbamoyl structure emerged effective inhibitors. The best activity was observed by dimethylaminopyridinium, analogues with a P-N distance of 3 or 4 methylene groups and pentadecyl or octadecylcarbamoyl structure (IC50 = 1.0-1.6 mumol/l).
Kertscher
H P
HP
Sektion Biowissenschaften, Universität Leipzig.
Schmidt
B
B
Ostermann
G
G
D001792:Blood Platelets / Q000187:drug effects; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / 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; D013329:Structure-Activity Relationship
D002219:Carbamates; D010743:Phospholipids; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors
PAF-Antagonisten mit Phospholipidstruktur. 4. Mitteilung: Alkylcarbamoylphospholipide mit Heteroaren- bzw. Heterocyclankopfgruppen und verändertem Phosphor-Stickstoff-Abstand; Synthese, Charakterisierung und Struktur-Wirkungs-Vergleich.