Synthesis and evaluation of platelet aggregation inhibitory activity of some 3-phenyl-pyrroloquinazolinones.

摘要: A series of 3-phenyl-2,7-dihydro-1H-pyrrolo[3,2-f]quinazolin-1-one derivatives (3-PPyQZ) was synthesized starting from 5-amino-indoles, via condensation with N-ethoxycarbonylthiobenzamides followed by thermal cyclization. On the basis their structural analogy reported anti-thrombin pyrroloquinazolines, were first tested for capacity to inhibit platelet aggregation. Some them had in vitro inhibitory effects on collagen and thrombin-induced aggregation in micromolar range, much higher inhibition than that shown some phenyl-pyrroloquinolinones. Experiments determine mechanism action most potent inhibitor (compound 18) indicated it acts at least two sites: one preceding agonist-induced increase cytosolic [Ca(2+)], following this step activation cascade. The compound also inhibited thrombin-evoked protein-Tyr-phosphorylation. Although is premature draw definitive conclusions, present results indicate 3-PPyQZ structure, quite 18, might constitute a point synthesis potential anti-thrombosis agents.