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Arzneimittelforschung 2004; 54(1): 9-14
DOI: 10.1055/s-0031-1296930
Cardiac Drugs · Cardiac Stimulants · Coronary Drugs
Editio Cantor Verlag Aulendorf (Germany)

Quantitative Structure-Activity Relationship Analysis of the Substituent Effects on the Binding Affinity of Derivatives of Trimetazidine

Svetoslav Slavov
Department of Chemistry, University of Sofia, Sofia, Bulgaria
,
Maria Djunlieva
Department of Chemistry, University of Sofia, Sofia, Bulgaria
,
Sonia Ilieva
Department of Chemistry, University of Sofia, Sofia, Bulgaria
,
Boris Galabov
Department of Chemistry, University of Sofia, Sofia, Bulgaria
› Author Affiliations
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Publication History

Publication Date:
25 December 2011 (online)

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Summary

In the present study a series of trimetazidine (1 – (2, 3, 4- trimethoxybenzyl)piperazine, CAS 5011-34-7) derivatives is subjected to quantitative structure-activity relationship (QSAR) analysis aiming at establishing the relationship between molecular structure and the binding affinity of the compounds to the respective receptor sites in the cells. Trimetazidine is used in the therapy of ischaemic heart disease. Literature data for the biological effect of the compounds are used. The derivatives studied include compounds with different substituents at the fourth position of the piperazine ring and a variation between the ortho-methoxy and orthohydroxy group in the benzyl residue. A statistically significant correlation between the Van der Waals volume of the substituents and the binding affinity of the respective compounds was found.

Zusammenfassung

Analyse der quantitativen Struktur-Wirkungs-Beziehungen von Substituenten auf die Bindungsaffinität von Trimetazi-din-Derivaten

In der vorliegenden Studie wurden Derivate von Trimetazidin (1-(2, 3, 4-Tri-methoxybenzyl)piperazin, CAS 5011-34-7) einer QSAR-Analyse (quantitative Struktur-Wirkungs-Beziehung) unterzogen, um die Beziehung zwischen Molekülstruktur und Bindungsaffinität der Verbindungen für die entsprechenden Rezeptorbindungsstellen in den Zellen zu ermitteln. Trimetazidin wird in der Therapie der ischämischen Herzkrankheit eingesetzt. Im Hinblick auf die biologischen Wirkungen werden Literaturdaten verwendet. Die untersuchten Derivate besaßen unterschiedliche Substituenten an der 4. Position im Piperazin-Ring sowie entweder eine 2-Methoxy- oder eine 2 Hydroxy-Gruppe im Benzen-Rest. Das Van der Vaals’sche Volumen der Substituenten und die Bindungsaffinität der entsprechenden Verbindungen korrelierten signifikant.

Key words

CAS 5011-34-7 - Trimetazidine derivatives, QSAR studies, substituent effects on binding affinity