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

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.

Authors
Voskressensky L.G. 2 , De Candia M. , Carotti A.1 , Borisova T.N. 2 , Kulikova L.N. 2 , Varlamov A.V. 2 , Altomare C.1
Journal
Journal of Pharmacy and Pharmacology
Publisher
Pharmaceutical Press
Number of issue
3
Language
English
Pages
323-332
Status
Published
Link
External link
DOI
10.1211/002235702676
Volume
55
Year
2003
Organizations
  • 1 Dipartimento Farmaco-Chimico, Universita degli Studi di Bari, Via Orabona 4, 70125 Bari, Italy
  • 2 Organic Chemistry Department, Russian Peoples' Friendship Univ., 6 Miklukho-Maklaia St., Moscow 117198, Russian Federation
Keywords
1 (4,5,7 trimethyl 4,5,6,7 tetrahydro 1h pyrrolo[3,2 c]pyridin 2 yl)ethanone; 2 (2 chlorobenzyl) 8 methoxy 2,3,4,5 tetrahydro 1h pyrido[4,3 b]indole oxalic acid; 2 benzylaminomethyl 4,5,6,7 tetrahydro 1h pyrrolo[3,2 c]pyridine; 2 ethyl 2,3,4,5 tetrahydro 1h pyrido[4,3 b]indole; 2 [(4,5,7 trimethyl 4,5,6,7 tetrahydro 1h pyrrolo[3,2 c]pyridin 2 yl)methylene]malononitrile; 2,2,2 trifluoro 1 (4,5,7 trimethyl 4,5,6,7 tetrahydro 1h pyrrolo[3,2 c]pyridin 2 yl)ethanol; 2,2,2 trifluoro 1 (4,5,7 trimethyl 4,5,6,7 tetrahydro 1h pyrrolo[3,2 c]pyridin 2 yl)ethanone; 2,3,4,5 tetrahydro 1h pyrido[4,3 b]indole derivative; 4,5,6,7 tetrahydro 1h pyrrolo[3,2 c]pyridine derivative; 4,5,7 trimethyl 4,5,6,7 tetrahydro 1h pyrrolo[3,2 c]pyridine 2 carbaldehyde oxime; 4,5,7 trimethyl 4,5,6,7 tetrahydro 1h pyrrolo[3,2 c]pyridine 2 carbonitrile; 5 acetyl 1 vinyl 4,5,6,7 tetrahydro 1h pyrrolo[3,2 c]pyridine derivative; 5 benzyl 4,5,6,7 tetrahydro 1h pyrrolo[3,2 c]pyridine; acetylsalicylic acid; adenosine diphosphate; adrenalin; n benzyl n [(4,5,7 trimethyl 4,5,6,7 tetrahydro 1h pyrrolo[3,2 c]pyridin 2 yl)methyl]amine monooxalic acid; n [(4,5,7 trimethyl 4,5,6,7 tetrahydro 1h pyrrolo[3,2 c]pyridin 2 yl)methyl]propane 1,3 diamine monooxalic acid; pyrrolo[3,2 c]pyridine derivative; thromboxane A2; ticlopidine; unclassified drug; adrenalin release; adult; article; calculation; comparative study; controlled study; dose response; drug potency; drug screening; drug structure; drug synthesis; experimentation; human; human cell; IC 50; in vitro study; lipophilicity; normal human; partition coefficient; physicochemical model; statistical analysis; structure activity relation; thrombocyte activation; thrombocyte aggregation inhibition; thrombocyte rich plasma
Date of creation
19.10.2018
Date of change
19.10.2018
Short link
https://repository.rudn.ru/en/records/article/record/81/
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