3D-QSAR design of novel antiepileptic sulfamides

Proposed pharmacophore for anticonvulsant activity, derived from a CoMFA that uses a training set of 27 AC drugs. New AC symmetric sulfamides were designed on its basis. A three-dimensional quantitative structure–activity relationship method, the comparative molecular field analysis (CoMFA), was app...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2007-02, Vol.15 (3), p.1556-1567
Main Authors: Gavernet, Luciana, Dominguez Cabrera, M. Josefina, Bruno-Blanch, Luis E., Estiú, Guillermina L.
Format: Article
Language:English
Subjects:
Animals
Anticonvulsant drugs
Anticonvulsants - chemical synthesis
Anticonvulsants - chemistry
Anticonvulsants - pharmacology
Anticonvulsants. Antiepileptics. Antiparkinson agents
Biological and medical sciences
CoMFA
Drug Design
Epilepsy - drug therapy
Female
Ligands
Male
Medical sciences
Mice
Models, Molecular
Molecular Structure
Neuropharmacology
Pharmacology. Drug treatments
Quantitative Structure-Activity Relationship
Structure-Activity Relationship
Sulfamides
Sulfonamides - chemical synthesis
Sulfonamides - chemistry
Sulfonamides - pharmacology
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Summary:Proposed pharmacophore for anticonvulsant activity, derived from a CoMFA that uses a training set of 27 AC drugs. New AC symmetric sulfamides were designed on its basis. A three-dimensional quantitative structure–activity relationship method, the comparative molecular field analysis (CoMFA), was applied to design new anticonvulsant symmetric sulfamides. The training set (27 structures) was comprised by traditional and new-generation anticonvulsant (AC) ligands that exhibit a potent activity in MES test. Physicochemical determinants of binding, such as steric and electrostatic properties, were mapped onto the molecular structures of the set, in order to interpret graphically the CoMFA results in terms of field contribution maps. The 3D-QSAR models demonstrate a good ability to predict the activity of the designed compounds ( r 2 = 0.967, q 2 = 0.756).
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2006.06.010