Quantitative structure-activity relationship analysis of the substituent effects on the binding affinity of derivatives of trimetazidine.
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 ortho-hydroxy 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.
Department of Chemistry, University of Sofia, Sofia, Bulgaria.
Svetoslav
S
Slavov
Maria
M
Djunlieva
Sonia
S
Ilieva
Boris
B
Galabov
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004563:Electrochemistry; D016014:Linear Models; D008928:Mitochondria / Q000378:metabolism; D008958:Models, Molecular; D000442:Octanols / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D011789:Quantum Theory; D012995:Solubility; D014292:Trimetazidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology; D014665:Vasodilator Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D014867:Water / Q000737:chemistry
D000442:Octanols; D014665:Vasodilator Agents; D014867:Water; D014292:Trimetazidine