SYNTHESIS AND ANTICONVULSANT ACTIVITY OF SOME NEWER SEMICARBAZONE DERIVATIVES
Abstract
A series of 4-(3-Chlorophenyl)-1-(substituted acetophenone) semicarbazones 3(a-j) was synthesized by starting with 3-chloroaniline which on reaction with sodium cyanate yielded 1-(3’-chlorophenyl) urea (1) followed by reaction with hydrazine hydrate in the presence of ethanol gave 4-(3’-chlorophenyl) semicarbazide (2). Compound (2) on condensation with substituted acetophenone gets converted in to final compounds 3(a-j). The purity of the newer compounds was checked by m.p. and TLC analysis. The structures of the newly synthesized compounds were characterized by FTIR, 1H NMR, EIMS-spectral data and elemental analysis. All the synthesized compounds were evaluated for their anticonvulsant activity by Maximal Electroshock (MES) method by using phenytoin as standard at a concentration of 30 mg/kg. The anticonvulsant effect of the newly synthesized compounds was assessed by absence or reduction of hind limb tonic extensor phase. Among the synthesized derivatives compounds 3e and 3j were found to be the most potent compounds in the series.
Keywords:
Anticonvulsant, MES method, SemicarbazoneDOI
https://doi.org/10.25004/IJPSDR.2012.040305References
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21. Yogeeshwari P, Sriram D, Thirumurgan R, Jeewanlal LR, Jit S, Raghvendran JV, Kavya R, Rakhra K, Sarasvat V. Synthesis of N4-(2,4-dimethylphenyl)semicarbazones as 4-aminobutyrate aminotransferase inhibitors.Acta Pharm. 2000; 56: 259-272.
22. Siddiqui N, Pandeya SN, Khan SA, Stables J, Rana A, Alam M, Arshad MF, Bhat MA. Synthesis and Anticonvulsant activity of sulfonamide derivatives-hydrophobic domain.Bioorg Med Chem Lett. 2007; 17: 235-259.
23. Murti Y, Agrawal T, Pathak D. Synthesis and Anticonvulsant activity of Substituted Benzaldehyde-4-aryl-thiosemicarbazones. Indian Drugs. 2010; 47(10): 19-27.
2. Kaminski K, Obniska J. Design, Synthesis and Anticonvulsant activity of N-phenylamino derivatives of 3, 3-dialkyl-pyrrolidine-2, 5-diones and hexahydro-isoindole-1, 3-diones. Bioorg Med Chem. 2008; 16: 4921-4931.
3. Obniska J, Kaminski K, Skrzynska D, Pichor J. Synthesis and Anticonvulsant activity of new N-[(4-arylpiperazin-1-yl)-alkyl] derivatives of 3-phenyl-pyrrolidine-2,5-dione. Eur J Med Chem. 2009; 44: 2224-2233.
4. Erington AC, Coyne L, Stihr T, Selve N, Lees G. Seeking a mechanism of action of novel anticonvulsant lacosamide. Neuropharmacol. 2006; 50: 1016-1029.
5. Librowsky T, Kubacka M, Meusel M, Scolari S, Muller CE, Gutschow M. Evaluation of Anticonvulsant and Analgesic effects of benzyl- and benzhydryl ureides. Eur J Pharmacol, 2007; 559: 138-149.
6. Jin HG, Sun XY, Chai KY, Piao HR, Quan ZS. Anticonvulsant and Toxicity Evaluation of some 7-alkoxy-4, 5-dihydro-[1, 2, 4]triazolo[4, 3-a]quinoline-1(2H)-ones. Bioorg Med Chem. 2006; 14: 6868-6873.
7. Flaherty PT, Greenwood TD, Manheim AL, Wolfe JF. Synthesis and Evaluation of N-(phenylacetyl) trifluoromethane sulfonamides as anticonvulsant agents. J Med Chem, 1996; 39: 1509-1513.
8. Guo LJ, Wei CX, Jia JH, Zhao LH, Quan ZS. Design and Synthesis of 5-alkoxy-[1, 2, 4]triazolo[4, 3-a]quinoline derivatives with anticonvulsant activity. Eur J Med Chem. 2009; 44: 954-958.
9. Chen J, Sun X, Chai K, Lee JS, Song MS, Quan ZS. Synthesis and Anticonvulsant evaluation of 4-(4-alkoxyphenyl)-3-ethyl-4H-1, 2, 4-triazoles as open-chain analogues of 7-alkoxyl-4, 5-dihydro[1, 2, 4] triazolo[4, 3-a]quinolines. Bioorg Med Chem. 2009; 15: 6775-6781.
10. Ho B, Venkatarangan PM, Cruse SF, Hinko CN, Anderson PH, Crider AM, Adloo AA, Roanc DS, Stables JP. Synthesis of 2-piperdinecarboxylic acid derivatives as potential anticonvulsants. Eur J Med Chem. 1998; 33: 23-30.
11. Blanch L, Galvez J, Domenech R. Topological virual screening: a way to find new anticonvulsant drugs from chemical diversity. Bioorg Med Chem. 2003; 13: 2749-2754.
12. Gitto R, Steffanio F, Agnello S, Luca LD, Sarro GD, Russo E, Vullo D, Supuran CT, Chimmiri A. Synthesis and Evaluation of Pharmacological profile of 1-aryl-6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-sulfonamides. Bioorg Med Chem. 2009; 17: 3659-3664.
13. Gavernet L, Barrios IA, Cravero MS, Blanch LE. Design, Synthesis and Anticonvulsant activity of some sulfamides. Bioorg Med Chem. 2007; 15: 5604-5614.
14. Yogeeshwari P, Sriram D, Jeewanlal LR, Jit S, Kumar SS, Stables JP. Synthesis and Anticonvulsant activity of 4-[2-(2, 6-dimethylphenyl amino) -2- oxoethylamino]-N-(substituted) butanamides: A pharmacophoric hybrid approach. Eur J Med Chem. 2002; 37: 231-236.
15. Lusczki JJ, Kocharov SL, Czuczwar SJ. N-(anilinomehyl)-p-isoprpoxy phenylsuccinimide potentiates the anticonvulsant action of phenobarbital and valproate in the mouse maximal electroshock induced seizure model. Neurosci. Res. 2009; 64: 267-272.
16. Azam F, Alkskas IA, Khokra SB, Prakash O. Synthesis of some novel N4-(naphtha[1,2-d]thiazol-2-yl)semicarbazides as potential anticonvulsants.Eur J Med Chem. 2009; 44: 203-211.
17. Siddiqui N, Rana A, Khan SA, Bhat MA, Haque SE. Synthesis of benzothiazole semicarbazones as novel anticonvulsants-The role of hydrophobic domain. Bioorg Med Chem Lett. 2007; 17: 4178-4182.
18. Verma M, Pandeya SN, Singh KA, Stables JP. Anticonvulsant activity of Schiff bases of Isatin derivative. Acta Pharm. 2004; 54: 49-56.
19. Yogeeshwari P, Thirumurgan R, Kavya R, Samuel JS, Stables J, Sriram D. 3-Chloro-2-methylphenyl-substituted semicarbazones: Synthesis and anticonvulsant activity.Eur J Med Chem. 2004; 39: 729-734.
20. Dimmock JR, Vashishtha SV, Stables JP. Anticonvulsant properties of various acetylhydrazones, oxamoylhydrazones and semicarbazones derived from aromatic and unsaturayed carbonyl compounds.Eur J Med Chem. 2000; 35: 241-248.
21. Yogeeshwari P, Sriram D, Thirumurgan R, Jeewanlal LR, Jit S, Raghvendran JV, Kavya R, Rakhra K, Sarasvat V. Synthesis of N4-(2,4-dimethylphenyl)semicarbazones as 4-aminobutyrate aminotransferase inhibitors.Acta Pharm. 2000; 56: 259-272.
22. Siddiqui N, Pandeya SN, Khan SA, Stables J, Rana A, Alam M, Arshad MF, Bhat MA. Synthesis and Anticonvulsant activity of sulfonamide derivatives-hydrophobic domain.Bioorg Med Chem Lett. 2007; 17: 235-259.
23. Murti Y, Agrawal T, Pathak D. Synthesis and Anticonvulsant activity of Substituted Benzaldehyde-4-aryl-thiosemicarbazones. Indian Drugs. 2010; 47(10): 19-27.
Published
01-07-2012
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“SYNTHESIS AND ANTICONVULSANT ACTIVITY OF SOME NEWER SEMICARBAZONE DERIVATIVES”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 4, no. 3, July 2012, pp. 195-8, https://doi.org/10.25004/IJPSDR.2012.040305.
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How to Cite
“SYNTHESIS AND ANTICONVULSANT ACTIVITY OF SOME NEWER SEMICARBAZONE DERIVATIVES”. International Journal of Pharmaceutical Sciences and Drug Research, vol. 4, no. 3, July 2012, pp. 195-8, https://doi.org/10.25004/IJPSDR.2012.040305.
