Abstract
In this paper, we describe the antinociceptive activity, molecular modeling and in silico ADMET screening of a series of sulphonyl-hydrazone and sulphonamide imidobenzene derivatives. Among these compounds, the sulphonyl-hydrazones 9 and 11 showed the most potent analgesic activity (ID50 = 5.1 and 6.8 μmol/kg, respectively). Interestingly, all derivatives evaluated in this study have a better analgesic profile than the control drugs, acetyl salicylic acid and acetaminophen. Derivative 9 was the most promising compound; with a level of activity that was 24 times higher than the control drugs. Our SAR study showed a relationship among the distribution of the frontier orbital HOMO coefficients, HOMO-LUMO energy gap of these molecules and their reactivity. The best analgesic compounds (including 6, 9, 10, 11 and 12) fulfilled the Lipinski “rule-of-five”, which is theoretically important for good drug absorption and permeation.
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de Oliveira, K.N., Souza, M.M., Sathler, P.C. et al. Sulphonamide and sulphonyl-hydrazone cyclic imide derivatives: Antinociceptive activity, molecular modeling and In Silico ADMET screening. Arch. Pharm. Res. 35, 1713–1722 (2012). https://doi.org/10.1007/s12272-012-1002-1
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DOI: https://doi.org/10.1007/s12272-012-1002-1