New 2-amino-thiazole-4-acetamides with antiplatelet activity.
In the Born test, 23 title compounds were synthesized and investigated for their antiplatelet activities against collagen, ADP, adrenaline, and platelet-activating factor (PAF) as inducers of the aggregation. Using collagen, three compounds with IC(50) values below 10 microM were found (3a, 3b, 3c) and 15 compounds with IC(50) values between 10 and 100 microM were determined. In general, a cyclohexylamino rest on an 4-carboxamide moiety is a pre-requisite for this pharmacological activity. A clear dependence from the substituent R(1) in the structural element Y is observed. The same is true for the spacer n in the 4-carboxamide substituent. Compound 3e showed strong ADP-antagonistic effects (IC(50) = 2.2 nM); 3c antagonized adrenaline (IC(50) = 2.8 nM), while 3n was highly effective against platelet-activating factor (IC(50) = 0.2 microM).
Rehse
Klaus
K
Institut für Pharmazie, Freie Universität Berlin, Berlin, Germany. rehiwer@zedat.fu-berlin.de
Baselt
Tobias
T
D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D015195:Drug Design; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000081:Acetamides; D010975:Platelet Aggregation Inhibitors; D013844:Thiazoles