Investigation on the antiplatelet activity of pyrrolo[3,2- c ]pyridine-containing compounds

Abstract

A series of 4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridines (THPPs), mostly C(2)-substituted derivatives, and some 2, 3, 4, 5-tetrahydro-1H-pyrido[4, 3-b]indoles (THPIs) were synthesized and tested in-vitro for their ability to inhibit aggregation of human platelet-rich plasma (PRP) induced by adenosine 5′-diphosphate (ADP) and adrenaline (epinephrine). 5-Benzyl THPP (3), 2-(benzylamino)methyl THPP (5f) and 2-ethyl THPI (6) moderately and dose-dependently inhibited platelet aggregation induced by adrenaline and, to a lesser extent, by ADP. These compounds inhibited the second phase of the PRP aggregation triggered by adrenaline, which largely depends upon thromboxane A2 production and ADP release. In the adrenaline-stimulated aggregation, the THPI derivative 6 was found to be nearly equipotent with aspirin, their IC50 values (concentration effecting 50% inhibition of aggregation) being 90 and 60 μM, respectively. A relation between activity and calculated octanol-water partition coefficient suggested that a log P value around 2.5 should be the optimal lipophilicity value for the activity of THPP-containing compounds.