New NO-donors with antithrombotic and vasodilating activities, Part 14. 1,3,4-Triazol-1-oles.
Five 1,3,4-triazol-1-oles (5a-f) with different alkyl, aryl, and arylalkyl substituents in 2,5-position were synthesized and tested for their antithrombotic properties. The 2,5-dimethyl derivative 5a was most active. 2 h after administration of 60 mg/kg to rats thrombus formation by a laser beam was inhibited by 42% in arterioles and by 33% in venules. At the same dose the blood pressure of SHR rats was slightly (5%) but significantly decreased even 4 h after application of 5a. This pattern of activities suggests a nitric oxide mediated mechanism of action. 1,1'-Azo-bis-ethanone oxime(7)-the synthetic precursor of 5a-inhibited the aggregation of blood platelet (Born test) with an IC50 = 15 mumol/L.
Rehse
K
K
Institut für Pharmazie I, Freien Universität Berlin, Germany.
Piechocki
D
D
Schober
M
M
Scheffler
H
H
Reitner
N
N
Unsöld
E
E
D000818:Animals; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D013927:Thrombosis / Q000188:drug therapy; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology
D005343:Fibrinolytic Agents; D014230:Triazoles; D014665:Vasodilator Agents