Design, synthesis and biological evaluation of some novel benzimidazole derivatives for their potential anticonvulsant activity

被引：0
作者：
Priyal Jain
Prakash Kumar Sharma
Harish Rajak
Rajesh Singh Pawar
Umesh Kumar Patil
Pradeep Kumar Singour
机构：
[1] VNS Institute of Pharmacy,Computational & Synthetic Laboratory, Department of Pharmaceutical Chemistry
[2] Guru Ghasidas University,Medicinal Chemistry Division, SLT Institute of Pharmaceutical Sciences
[3] Institute of Pharmaceutical Sciences,Medicinal Chemistry Division
[4] Guru Ghasidas University,undefined
来源：
Archives of Pharmacal Research | 2010年 / 33卷
关键词：
QSAR; Anticonvulsant; Benzimidazole; MES and PTZ convulsions;
D O I：
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摘要：
Selective GABAA receptor ligands are widely used clinically to reduce the occurrence of convulsions. Hence there is an intense interest in developing new benzimidazole derivatives demonstrating high selectivity and high affinity for GABAA receptors. With the purpose of designing new chemical entities with an enhanced binding affinity for GABAA/BZd receptor complex, we carried out a QSAR study on benzotriazine derivatives. We studied 28 potent GABAA receptor ligands; derivatives of benzotriazines, using a combination of various tested physicochemical, steric, electronic and thermodynamic descriptors to determine the quantitative correlation between binding affinity and structural features. The developed and validated final model showed a good correlative and predictive ability expressed by a squared correlation co-efficient (r2) of 0.954. The equation indicated that the binding affinity is strongly dependent upon the thermodynamic properties (CDE, DDE and PC). Correlation between these properties and anticonvulsant activity was used to synthesize compounds possessing potent anticonvulsant activity. Most of the compounds showed an ability to inhibit the maximum electroshock (MES) and pentylenetetrazole (PTZ)-induced convulsions. Compound 1A, i.e. 2-(4-Chloro-phenyl)-5-nitro-1H-benzimidazole exhibited maximum activity in both the convulsion models.
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页码：971 / 980
页数：9
相关论文
共 110 条
[1]  
Abbas S.(2004)Anticonvulsant activities of new 1,4-dihydropyridine derivatives containing 4-nitroimidazolyl substituents DARU 12 81-86
[2]  
Rastkari N.(2004)N-Substituted amino acid N-benzylamides: synthesis, anticonvulsant, and metabolic activities Bioorg. Med. Chem. 12 3079-3096
[3]  
Sharifzadeh M.(2007)Synthesis and anticonvulsant evaluation of 4-(4-alkoxylphenyl)-3-ethyl-4H-1, 2, 4-triazoles as openchain analogues of 7-alkoxyl-4,5-dihydro [1, 2, 4] triazolo [4, 3-a] quinolines Bioorg. Med. Chem. 15 6775-6781
[4]  
Beguin C.(1986)Anticonvulsant activity of 2- and 3-aminobenzanilides J. Med. Chem. 29 1534-1537
[5]  
Arnaud L. T.(2006)Synthesis, anticonvulsant, and antiinflammatory evaluation of some new benzotriazole and benzofuran-based heterocycles Bioorg. Med. Chem. 14 3672-3680
[6]  
Stables J. P.(2006)Synthesis, pharmacology and molecular modeling of N-substituted 2-phenyl-indoles and benzimidazoles as potent GABA Eur. J. Med. Chem. 41 985-990
[7]  
Voyksner R. D.(2008) agonists Bioorg. Med. Chem. 16 4471-4489
[8]  
Kohn H.(2009)Novel 3-aroylpyrazolo [5,1-c][1,2,4] benzotriazine 5-oxides 8-substituted, ligands at GABA Eur. J. Med. Chem. 44 954-958
[9]  
Chen J.(1962)/benzodiazepine receptor complex: Synthesis, pharmacological and molecular modeling studies Nature 194 178-180
[10]  
Sun X. Y.(1996)Design and synthesis of 5-alkoxy-[1,2,4]triazolo[4,3-a]quinoline derivatives with anticonvulsant activity Chem. Rev. 96 1045-1076
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