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 A(2) 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 microM, 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.

Synthesis of Novel Benzo[b][1,6]naphthyridine Derivatives and Investigation of Their Potential as Scaffolds of MAO Inhibitors

“…Here, we describe the first example of the formation of tetrahydroazocino[4,5- b ]quinolines; however, such transformations have been studied for other heterocyclic systems annulated with the tetrahydropyridine fragment and the mechanism of azocine fragment formation has been presented [ 36 , 37 , 38 , 39 , 40 , 41 ].…”

Investigating 1,2,3,4,5,6-hexahydroazepino[4,3-b]indole as scaffold of butyrylcholinesterase-selective inhibitors with additional neuroprotective activities for Alzheimer's disease

“…Selective BChE inhibitors usually contain polycyclic structures [24][25][26][27], such as compound 5, ethopropazine [28,29], quinazolinimine-based derivatives [30,31], carbazole and indolpiperidines [32,33]. Previously, some of us reported efficient syntheses of partially hydrogenated pyrrole-and indole-fused azaheterocycles with six-to-eight-membered ring size [34][35][36], as scaffolds of novel bioactive compounds, such as antiplatelet [37,38], antimicrobial [39], antioxidant agents [40,41] and AChE inhibitors [42][43][44]. More recently, some N 6 -substituted partially hydrogenated azepino [4,3-b]indole derivatives showed selective inhibition of BChE [45].…”