Abstract
BackgroundLipophilicity is a physicochemical property of an essential importance in medicinal chemistry; therefore, fast and reliable measurement of lipophilicity will affect greatly the drug discovery process.ResultsA series of N-benzenesulfonamide-1H-pyrazoles, oximes and hydrazones as celecoxib analogues was investigated with regard to their retention behavior using reversed-phase high performance liquid chromatography (RP-HPLC). The mobile phases employed for this study consist of a mixture of water and methanol in different proportions. In addition, the stationary phase utilized for this separation was C18 silanized silica gel and using 200 nm as a detection wavelength. The retention behavior of the investigated compounds was determined based on practical determination of log k at different concentrations of methanol (as an organic modifier) in the mobile phase ranging from 60 to 80%. It was observed that the retention of these compounds (expressed as log k) decreased in a linear manner with increasing the concentration of methanol. High correlation coefficients (more than 0.90 in most cases) were obtained for the relationship between the volume fraction of the organic solvent and the retention values represented as log kw. A comparative evaluation was carried out between chromatographically-obtained lipophilicity parameters (represented as lipophilicity chromatographic index log kw or isocratic chromatographic hydrophobicity index, varphi0) and the computationally calculated log P values (miLogP, ALOGP, ACD/Labs and ALOGPs).ConclusionIt was found that a good correlation exists between the experimental and computed log P values. In the future, these results can give a deep insight about the anti-inflammatory and analgesic activity of the newly synthesized compounds.
Highlights
ResultsA series of N-benzenesulfonamide-1H-pyrazoles, oximes and hydrazones as celecoxib analogues was inves‐ tigated with regard to their retention behavior using reversed-phase high performance liquid chromatography (RPHPLC)
Lipophilicity is a paramount descriptor which represents an essential part in design of new medications with required biological action [1]
Lipophilicity is a fundamental molecular property which is defined as the logarithm of the octanol– water partition coefficient, which is, in turn, expressed as the non-ionized drug spread ratio between the two phases of octanol and water [7]. log P measurements by different experimental protocols are illustrated in detail by the Organization for Economic Cooperation and Development (OECD) guidelines as test No 107, which is Shake Flask method [8], and Test No 123, which is the Slow Stirring method [9]
Summary
A series of N-benzenesulfonamide-1H-pyrazoles, oximes and hydrazones as celecoxib analogues was inves‐ tigated with regard to their retention behavior using reversed-phase high performance liquid chromatography (RPHPLC). The mobile phases employed for this study consist of a mixture of water and methanol in different proportions. The retention behavior of the investigated compounds was determined based on practical determi‐ nation of log k at different concentrations of methanol (as an organic modifier) in the mobile phase ranging from 60 to 80%. It was observed that the retention of these compounds (expressed as log k) decreased in a linear manner with increasing the concentration of methanol. High correlation coefficients (more than 0.90 in most cases) were obtained for the relationship between the volume fraction of the organic solvent and the retention values represented as log kw. A comparative evaluation was carried out between chromatographically-obtained lipophilicity parameters (repre‐ sented as lipophilicity chromatographic index log kw or isocratic chromatographic hydrophobicity index, φ0) and the computationally calculated log P values (miLogP, ALOGP, ACD/Labs and ALOGPs)
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