Antiaggregating and antithrombotic activities of new 1, 2, 3-triazolecarboxamides.
Twenty five new triazolecarboxamides related to YC-1 were prepared and tested for their antiplatelet (in vitro) and antithrombotic (in vivo) activities. Five of them inhibited the aggregation of blood platelets (Born test, inducer collagen) with IC50 values between 90 and 130 microM. Nine compounds exhibited significant antithrombotic properties with an inhibition of thrombus formation between 11 and 7%. Only one compound (8c) showed both, in vitro and in vivo effects. In vitro, the most active compounds were 11c and 12d. They inhibit platelet aggregation with IC50 = 90 and 95 microM. In vivo, 10a showed the strongest inhibition of thrombus formation with 11% in arterioles (5% in venules) after a single oral dose of 60 mg/kg. With serotonin as inducer both, 11c and 12d, showed lower IC50 values namely 25 or 30 microM, respectively. Additional antiplatelet activities were found for 11c against adrenaline (IC50 = 25 microM) and for 12d against platelet activating factor (PAF) (IC50 = 15 microM) as inducer.
Cwiklicki
Anke
A
Institut für Pharmazie, Freie Universität Berlin, Berlin, Germany.
Rehse
Klaus
K
D000818:Animals; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000187:drug effects / Q000502:physiology; D007191:Indazoles / Q000138:chemical synthesis / Q000378:metabolism; D007834:Lasers / Q000009:adverse effects; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology
D005343:Fibrinolytic Agents; D007191:Indazoles; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D010727:Phosphoric Diester Hydrolases; D006162:Guanylate Cyclase