Sulphonamide and sulphonyl-hydrazone cyclic imide derivatives: antinociceptive activity, molecular modeling and in silico ADMET screening.
Arch Pharm Res
; 35(10): 1713-22, 2012 Oct.
Article
en En
| MEDLINE
| ID: mdl-23139121
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 (ID(50) = 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Sulfonamidas
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Diseño de Fármacos
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Hidrazonas
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Analgésicos
/
Imidas
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Límite:
Animals
Idioma:
En
Año:
2012
Tipo del documento:
Article