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Synthesis, in silico metabolic and toxicity prediction of some novel imidazolinones derivatives as potent anticonvulsant agents.
- Source :
-
Journal of enzyme inhibition and medicinal chemistry [J Enzyme Inhib Med Chem] 2012 Apr; Vol. 27 (2), pp. 201-7. Date of Electronic Publication: 2011 Jun 03. - Publication Year :
- 2012
-
Abstract
- A series of 1,2,4-trisubstituted 5-imidazolinone derivatives were synthesized by Erlenmeyer condensation of benzoylglycine (hippuric acid) with different aldehydes in the presence of sodium acetate and acetic anhydride. The derivatives of the compounds were prepared by condensation of some known sulpha drugs with 5-oxazolone derivatives. The anticonvulsant activity of the compounds was determined by the protection of pentylenetetrazole-induced convulsions that was ranged from 10 to 60%. The compounds with p-OCH₃, p-OH and o-Cl substitutions in the phenyl ring on 4(th) position of the imidazolinone ring exhibited good anticonvulsant activity. In silico metabolic and toxicity studies showed that all the compounds in the series are not likely to exhibit toxicity except the compounds IIIa, IIIb, VIa and VIb, that is predicted to show 29% mutagenicity and 53% irritation in comparison to the other compounds. The predicted lethal effect and hERG toxicity of the compounds showed that IIa, IVa, Va and Vb might be toxic at higher concentrations. The results successfully establish the synthesized imidazolinone derivatives as novel compounds with anticonvulsant properties, low predicted cardiotoxicity and lethal effects thus can be promising leads for further development as novel anticonvulsants.
- Subjects :
- Animals
Convulsants toxicity
Mice
Molecular Structure
Pentylenetetrazole toxicity
Seizures chemically induced
Software
Structure-Activity Relationship
Anticonvulsants chemical synthesis
Anticonvulsants pharmacology
Anticonvulsants toxicity
Imidazolines chemical synthesis
Imidazolines pharmacology
Imidazolines toxicity
Seizures prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1475-6374
- Volume :
- 27
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of enzyme inhibition and medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 21635210
- Full Text :
- https://doi.org/10.3109/14756366.2011.584191