Synthesis and pharmacological evaluation of 2,3-dialkylindoles, "in vitro" inhibitors of thrombin-induced platelet aggregation.
A series of 2,3-dialkylindoles (1-5) have been prepared and tested as antithrombotic agents. The whole class showed in vitro interesting activity in the inhibition of thrombin-induced aggregation. Among these compounds some ones showed activity comparable to standards also in the inhibition of collagen-induced aggregation. Owing to a very fast metabolic degradation through a beta-oxidative mechanism, a drastic decrease of activity in several tests ex vivo or in vivo was observed.
Arcari
M
M
Istituto Biochimico Italiano, IBI Sud, Research Laboratories, Aprilia, (LT).
Aveta
R
R
Brandt
A
A
Cecchetelli
L
L
Corsi
G B
GB
Solinas
F
F
D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D010976:Platelet Count / Q000187:drug effects; D051381:Rats; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013923:Thromboembolism / Q000517:prevention & control
D007211:Indoles; D010975:Platelet Aggregation Inhibitors; D013917:Thrombin