Application of Chromatographic Data in QSAR Studies of 3-[ω-(4-Arylpiperazin-1-yl)alkyl]pyrimido[5,4-c]quinolin-4(3H)-one Derivatives as 5-HT1A Receptor Ligands

• Published in: Journal of chromatographic science Vol. 52; no. 7; pp. 596 - 603
• Main Authors: Żydek, Grażyna, Brzezińska, Elżbieta, Stańczak, Andrzej, Lewgowd, Wiesława
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-08-2014
• Subjects: Amino Acids - chemistry; Amino Acids - metabolism; Chromatography, Thin Layer - methods; Drug Discovery; Ligands; Linear Models; Models, Chemical; Piperazines - analysis; Piperazines - chemistry; Piperazines - metabolism; Quantitative Structure-Activity Relationship; Receptor, Serotonin, 5-HT1A; Reproducibility of Results
• ISSN: 0021-9665; 1945-239X
• DOI: 10.1093/chromsci/bmt082

The activity of several 3-[ω-(4-arylpiperazin-1-yl)alkyl]pyrimido[5,4-c]quinolin-4(3H)-ones (LCAPs) with well-defined serotonin 1A (5-HT1A) receptor affinity was described by using chromatographic and calculated physicochemical parameters in quantitative structure–activity relationship analysis. Normal-phase thin-layer chromatography plates impregnated with solutions of L-aspartic acid, L-serine, L-phenylalanine, L-tryptophan, L-tyrosine, L-asparagine, L-threonine and their mixtures (denoted as S1–S11 biochromatographic models) were used with two mobile phases as a model of the interaction between LCAP and 5-HT1A receptors. Molecular descriptors for the investigated compounds were calculated by using HyperChem and ACD/Labs programs. The significant relationship explains that 82% of the variance was successfully validated by leave-one-out and leave-many-out tests. The results demonstrated that this model has significant predictive ability and can be used for the preliminary screening of newly synthesized potential 5-HT1A receptor ligands.