Efecto de Piridazino (4-5-b)indoles en Trombano Sintetasa

Abstract

Se han realizado los ensayos como inhibidores selectivos de Tromboexa no Sintetasa de siete comouestos de éstructura relativa a piridazino (45-b)indol. La inhibición en la segunda onda de agregación inducida en plaquetas humanas por ADP, en la inducida por ácido araquidónico y por prostaglandina H₂ (PGH₂), así como en la producción de Tromboxano B₂ (TXB₂), han permitido determinar que dos de estos compuestos, 3,4-dihidro-4-oxo-5H-piridazino (4,5-b)indol (I) y 3,4-dihidro-4-oxo-5H-8-benciloxi-piridazino (4, 5-b)indol (VII), son nuevos inhibidores selectivos de este sistema enzimático.

Assays were performed which identified seven compounds with the general structure indol-piridazine (4,5-b) as selective inhibitors of Thromboxane Synthetase. Compounds whose activities includes inhibition of human platelet aggregation induced by Arachidonic acid (AA) and Prostaglandin H₂ (PGH₂), and inhibition of the second wave of platelet aggregation induced by ADP, were subjected to radioimmunoassay studies to measue TXB₂ and PGE₂ levels in the samples using AA as the aggregating agent. This work has determined that two of the compounds, 3,4-dihydro-4-oxo-5H-pyridazino-(4,5-b)indole(I) and 3,4-dihydro-4-oxo-5H 8-benzyloxypyridazino (4,5-b)indole (VII), are new selective inhibitors of this enzymatic system