New indole and triazino[5,4-b]indol-4-one derivatives: synthesis and studies as inotropics and inhibitors of blood platelet aggregation.
New triazino[5,4-b]indol-4-one derivatives carrying amino groups in position 3 were synthetized and tested as inotropic agents and inhibitors of platelet aggregation. 2h, 2p, 5p, and 6g are the most active as inotropic agents. Compounds were tested as inhibitors of platelet aggregation induced by adenosine 5'-diphosphate (ADP) and arachidonic acid (AA) (guinea pig whole blood). 2k, 2p, 5o, 6d, 6m, and 6o are the most active as inhibitors of the platelet aggregation induced by AA. 6d, 6h, and 6o are most active compounds also in the aggregation induced by ADP. Radioimmunoassay studies, following AA induced aggregation, measuring thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were carried out on compounds 2b, 2d, 2f, 2g, 2h, 2i, 2k, 2m, 2o, 2p, 2r, 5i, 5j, 5k, 5r, and 5f, which inhibit platelet aggregation induced by AA. None of the compounds tested turned out to be selective inhibitors. Compounds 2h and 2p showed both inotropic and platelet aggregation inhibiting activity.
Monge
A
A
Centre of Investigation in Applied Pharmacobiology, University of Navarre, Pamplona, Spain.
Aldana
I
I
Font
M
M
Arraras
J A
JA
Santiago
E
E
Lopez-Unzu
M J
MJ
Martínez-de Irujo
J J
JJ
Alberdi
E
E
Fernández-Alvárez
E
E
D000818:Animals; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D014227:Triazines / Q000138:chemical synthesis* / Q000494:pharmacology
D007211:Indoles; D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D014227:Triazines