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Design and Synthesis of Novel N-(4-(Pyridin-2-yloxy)benzylidene)-4-[4-(substituted)phenyl]semicarbazides as Potential Anticonvulsant Agents
Corresponding Author(s) : Laxmi Tripathi
Asian Journal of Chemistry,
Vol. 30 No. 10 (2018): Vol 30 Issue 10, 2018
Abstract
A new series of N-(4-(pyridin-2-yloxy)benzylidene)-4-[4-(substituted)phenyl]semicarbazides (PSSD1-8) were designed and synthesized keeping in view the structural requirement of pharmacophore and evaluated for their possible anticonvulsant activity. All the derivatives were synthesized by the given scheme and reaction process was monitored by thin layer chromatography. The structure of synthesized derivatives was confirmed by FT-IR, 1H NMR, mass spectroscopy and elemental analysis. The anticonvulsant activity was established after intraperitoneal administration in MES and scMET seizure models. The most active compound of the series was 1-(4-(pyridin-2-yloxy)-benzylidene)-4-p-tolylsemicarbazide (PSSD5). A molecular docking study was carried out in order to assess the interaction and binding modes with target receptor/enzyme. Titled compounds were found to strongly bind to human gamma-aminobutyric acid receptor (GABAAR-β3). A computational study was also carried to predict the pharmacokinetic properties of the synthesized compounds.
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- R.G. Greenberg, C. Melloni, H. Wu, D. Gonzalez, L. Ku, K.D. Hill, C.P. Hornik, N. Zheng, W. Jiang, M. Cohen-Wolkowiez and J.T. Guptill, Clin. Neuropharmacol., 39, 232 (2016); https://doi.org/10.1097/WNF.0000000000000172.
- M.J. Ahsan, Cent. Nerv. Syst. Agents Med. Chem., 13, 148 (2013); https://doi.org/10.2174/18715249113136660016.
- D.K. Jain, A. Singh, V.K. Patel, R. Veerasamy, N. Aggarwal and H. Rajak, Cent. Nerv. Syst. Agents Med. Chem., 17, 30 (2017); https://doi.org/10.2174/1871524916666160411143941.
- S.N. Pandeya, A.A. Khan and A. Srivastava, J. Chem. Pharm. Res., 3, 456 (2011).
- L. Tripathi, R. Singh and J.P. Stables, Eur. J. Med. Chem., 46, 509 (2011); https://doi.org/10.1016/j.ejmech.2010.11.030.
- A. Jain, S. Patil and A. Gajbhiye, Int. J. Pharmacol. Pharm. Technol., 1, 2277 (2015).
- L. Tripathi, P. Kumar, R. Singh and J.P. Stables, Eur. J. Med. Chem., 47, 153 (2012); https://doi.org/10.1016/j.ejmech.2011.10.038.
- R.L. Krall, J.K. Penry, B.G. White, H.J. Kupferberg and E.A. Swinyard, Epilepsia, 19, 409 (1978); https://doi.org/10.1111/j.1528-1157.1978.tb04507.x.
- E.A. Swinyard, J.H. Woodhead, H.S. White and M.R. Franklin, Antiepileptic Drugs, Raven-Press, New York, USA, vol. III, pp. 989-995 (1989).
- P. Yogeeswari, D. Sriram, V. Saraswat, J.V. Ragavendran, M.M. Kumar, S. Murugesan, R. Thirumurugan and J.P. Stables, Eur. J. Pharm. Sci., 20, 341 (2003); https://doi.org/10.1016/j.ejps.2003.08.002.
- P. Ertl, B. Rohde and P. Selzer, J. Med. Chem., 43, 3714 (2000); https://doi.org/10.1021/jm000942e.
- C.A. Lipinski, L. Lombardo, B.W. Dominy and P.J. Feeney, Adv. Drug Deliv. Rev., 46, 3 (2001); https://doi.org/10.1016/S0169-409X(00)00129-0.
- Molinspiration Cheminformatics, Bratislava, Slovak Republic. http://www.molinspiration.com/servies/properties.html [accessed 16.08.2017].
- Y.H. Zhao, M.H. Abraham, J. Le, A. Hersey, C.N. Luscombe, G. Beck, B. Sherborne and I. Cooper, Pharm. Res., 19, 1446 (2002); https://doi.org/10.1023/A:1020444330011.
- V.A. Farrar, M. Ciechanowicz-Rutkowska, J. Grochowski, P. Serda, T. Pilati, G. Filippini, C.N. Hinko, A. El-Assadi and J.A. Moore, J. Med. Chem., 36, 3517 (1993); https://doi.org/10.1021/jm00075a005.
References
R.G. Greenberg, C. Melloni, H. Wu, D. Gonzalez, L. Ku, K.D. Hill, C.P. Hornik, N. Zheng, W. Jiang, M. Cohen-Wolkowiez and J.T. Guptill, Clin. Neuropharmacol., 39, 232 (2016); https://doi.org/10.1097/WNF.0000000000000172.
M.J. Ahsan, Cent. Nerv. Syst. Agents Med. Chem., 13, 148 (2013); https://doi.org/10.2174/18715249113136660016.
D.K. Jain, A. Singh, V.K. Patel, R. Veerasamy, N. Aggarwal and H. Rajak, Cent. Nerv. Syst. Agents Med. Chem., 17, 30 (2017); https://doi.org/10.2174/1871524916666160411143941.
S.N. Pandeya, A.A. Khan and A. Srivastava, J. Chem. Pharm. Res., 3, 456 (2011).
L. Tripathi, R. Singh and J.P. Stables, Eur. J. Med. Chem., 46, 509 (2011); https://doi.org/10.1016/j.ejmech.2010.11.030.
A. Jain, S. Patil and A. Gajbhiye, Int. J. Pharmacol. Pharm. Technol., 1, 2277 (2015).
L. Tripathi, P. Kumar, R. Singh and J.P. Stables, Eur. J. Med. Chem., 47, 153 (2012); https://doi.org/10.1016/j.ejmech.2011.10.038.
R.L. Krall, J.K. Penry, B.G. White, H.J. Kupferberg and E.A. Swinyard, Epilepsia, 19, 409 (1978); https://doi.org/10.1111/j.1528-1157.1978.tb04507.x.
E.A. Swinyard, J.H. Woodhead, H.S. White and M.R. Franklin, Antiepileptic Drugs, Raven-Press, New York, USA, vol. III, pp. 989-995 (1989).
P. Yogeeswari, D. Sriram, V. Saraswat, J.V. Ragavendran, M.M. Kumar, S. Murugesan, R. Thirumurugan and J.P. Stables, Eur. J. Pharm. Sci., 20, 341 (2003); https://doi.org/10.1016/j.ejps.2003.08.002.
P. Ertl, B. Rohde and P. Selzer, J. Med. Chem., 43, 3714 (2000); https://doi.org/10.1021/jm000942e.
C.A. Lipinski, L. Lombardo, B.W. Dominy and P.J. Feeney, Adv. Drug Deliv. Rev., 46, 3 (2001); https://doi.org/10.1016/S0169-409X(00)00129-0.
Molinspiration Cheminformatics, Bratislava, Slovak Republic. http://www.molinspiration.com/servies/properties.html [accessed 16.08.2017].
Y.H. Zhao, M.H. Abraham, J. Le, A. Hersey, C.N. Luscombe, G. Beck, B. Sherborne and I. Cooper, Pharm. Res., 19, 1446 (2002); https://doi.org/10.1023/A:1020444330011.
V.A. Farrar, M. Ciechanowicz-Rutkowska, J. Grochowski, P. Serda, T. Pilati, G. Filippini, C.N. Hinko, A. El-Assadi and J.A. Moore, J. Med. Chem., 36, 3517 (1993); https://doi.org/10.1021/jm00075a005.