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1 Polish Journal of Chemistry

1 2004

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Synthesis, Pharmacological Properties and SAR of New 1,4-Disubstituted Pierazine Derivatives with Hypnotic-Sedative Activity

Chilmonczyk Z., Mazgajska M., Chojnacka-Wójcik E., Tatarczyńska E., Kłodzińska A., Ulman M.

Polish Journal of Chemistry

2004

Vol. 78 / nr 8

1027-1037

Synthesis, chromatographic behaviour, pharmacological data and structure activity relationship (SAR) studies of some 1-(pyrimidin-2-yl)piperazine derivatives 1-13 are reported. The hydrophobic indices and chromatographic retention factors of the compounds exhibited statistically significant linear correlation with the calculated lipophilicities. The highest hypnotic-sedative activity as measured in loss of the righting reflex, rota-rod and spontaneous locomotor activity tests exhibited compound6 possessing n-hexyl R substituent. The hypnotic activity of compounds 1-13 measured in loss of the righting reflex test could be described with the aid of hydrophobic indices in terms of Hansch parabolic relationship for structurally related group of compounds (separately for compounds withR= alkyl orR= cycloalkyl). The necessity to describe the pharmacological activity for aliphatic and alicyclic series with 2 different equations corresponded well to the observed difference in the pharmacological properties between the both