Eight novel antitumour and analgesic active 8-aryl-2,6,7,8-tetrahydroimidazo[2,1-c][1,2,4]triazine-3,4-diones (1-8) have been obtained as a bioactive set of substances and their lipophilicity has been studied. The logk values of fifteen reference compounds and eight newly synthesised imidazotriazine-3,4-dione derivatives were determined by reversed-phase high performance liquid chromatography (RP-HPLC) using mixtures of methanol and water as mobile phases with different methanol concentrations. The relationships between logk values of a set of reference compounds (fifteen compounds) and investigated ones (eight compounds) and concentration of methanol was used for determination of the logkwater values by extrapolation. The partition coefficients (logP) values for reference compounds measured experimentally were taken from the literature. The calibration equation was then obtained for the standards of known lipophilicity (logPHPLC) and logkwater. In next step the partition coefficients of new synthesised solutes were calculated from the calibration equation. For the comparison purpose, additionally the partition coefficients (logPcalc.) of the examined imidazotriazine-3,4-diones were calculated by means of the Pallas 220.127.116.11. software. It was found that logkwater values as a lipophilicity measure of derivatives correlate well with partition coefficients measured experimentally (logPHPLC). Correlation between the logPHPLC and the logarithm of partition coefficient calculated by Pallas software (logPcalc.) is not so satisfactory as that for values determined experimentally. Furthermore, it has been found that the lipophilicity variation of investigated imidazotriazine-3,4-diones (1-8) correlates well with their acute toxicity expressed as log(1/LD50). The drug-likeness of all the bioactive 8-aryl-2,6,7,8-tetrahydroimidazo[2,1-c][1,2,4]triazine-3,4-diones was assessed on the basis of their structural properties by applying Lipniski's rule of five. The solutes have all four parameters important for the favourable pharmacokinetics in the human body that would make them likely orally active drugs in humans.
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