Synthesis and Anticonvulsant Activity Evaluation of 2-Phenyl-2H-benzo[e][1,3]oxazin-4(3H)-ones

Li-Jing Cui; Jun Guo; Guo-Hua Gong; Zhe-Shan Quan

doi:10.14233/ajchem.2014.15725

Issue

Vol. 26 No. 9 (2014): Vol 26 Issue 9

Issue Published : April 28, 2014

This work is licensed under a Creative Commons Attribution 4.0 International License.

Synthesis and Anticonvulsant Activity Evaluation of 2-Phenyl-2H-benzo[e][1,3]oxazin-4(3H)-ones

https://doi.org/10.14233/ajchem.2014.15725

Li-Jing Cui

Department of Pharmacy, Guangdong Food and Drug Vocational College, Guangzhou 510520, P.R. China

Jun Guo

College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, P.R. China

Guo-Hua Gong

Institute of Medicinal Chemistry, Inner Mongolia University for Nationalities, Tongliao 028002, Inner Mongolia Autonomous Region, P.R. China

Zhe-Shan Quan

College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, P.R. China

Corresponding Author(s) : Guo-Hua Gong

gongguohua0211@163.com

Asian Journal of Chemistry, Vol. 26 No. 9 (2014): Vol 26 Issue 9
Article Published : April 29, 2014

Abstract

A series of new 2-phenyl-2H-benzo[e][1,3]oxazin-4(3H)-one derivatives (1a-1t) were designed based on the known anticonvulsant activity of quinolinone derivatives. All target compounds 1a-1t, characterized by IR, ¹H NMR and MS, have been evaluated for their anticonvulsant activity against MES-induced seizures. The pharmacological results showed that all the compounds displayed some degree of anticonvulsant activity. Among them, 2-phenyl-2,3-dihydrobenzo[e][1,3]oxazin-4-one (1a) and 2-(2-fluorophenyl)-2,3-dihydrobenzo[e][1,3]oxazin-4-one (1b) were considerd more promising because of their lower ED₅₀ (34.1 and 28.4 mg/kg) and higher protective index (11.1 and 8.0).

Keywords

Anticonvulsant 1-Isoquinolinone Maximal electroshock test Neurotoxicity Benzo[e][1,3]oxazin-4(3H)-one

Cui, L.-J., Guo, J., Gong, G.-H., & Quan, Z.-S. (2014). Synthesis and Anticonvulsant Activity Evaluation of 2-Phenyl-2H-benzo[e][1,3]oxazin-4(3H)-ones. Asian Journal of Chemistry, 26(9), 2553–2556. https://doi.org/10.14233/ajchem.2014.15725

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References

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T.W. Strine, R. Kobau, D.P. Chapman, D.J. Thurman, P. Price and L.S. Balluz, Epilepsia, 46, 1133 (2005); doi:10.1111/j.1528-1167.2005.01605.x.

O.J. McNamara, L.L. Brunton, J.S. Lazo and K.L. Parker, The Pharmacological Basis of Therapeutics, McGraw-Hill: New York (2006).

P. Kwan and M.J. Brodie, N. Engl. J. Med., 342, 314 (2000); doi:10.1056/NEJM200002033420503.

B.B. Spear, Epilepsia, 42(s5), 31 (2001); doi:10.1046/j.1528-1157.2001.0420s5031.x.

J. Rémi, A. Hüttenbrenner, B. Feddersen and S. Noachtar, Epilepsy Res., 88, 145 (2010); doi:10.1016/j.eplepsyres.2009.10.007.

K.J. Meador, J. Clin. Psychiatry, 64(Suppl. 8), 30 (2003).

V. Belcastro, P. Striano, G. Gorgone, C. Costa, C. Ciampa, D. Caccamo, L.R. Pisani, G. Oteri, M.G. Marciani, U. Aguglia, S. Striano, R. Ientile, P. Calabresi and F. Pisani, Epilepsia, 51, 274 (2010); doi:10.1111/j.1528-1167.2009.02303.x.

H.P. Bootsma, L. Ricker, Y.A. Hekster, J. Hulsman, D. Lambrechts, M. Majoie, A. Schellekens, M. de Krom and A.P. Aldenkamp, Seizure, 18, 327 (2009); doi:10.1016/j.seizure.2008.11.006.

G.M. Kennedy and S.D. Lhatoo, CNS Drugs, 22, 739 (2008); doi:10.2165/00023210-200822090-00003.

P.E. Penovich and L.J. Willmore, Epilepsia, 50, 37 (2009); doi:10.1111/j.1528-1167.2009.02234.x.

Z.S. Quan, J.M. Wang, J.R. Rho, K.C. Kwak, H.C. Kang, C.S. Jun and K.Y. Chai, Korean Chem. Soc., 26, 1757 (2005); doi:10.5012/bkcs.2005.26.11.1757.

Z.T. Piao, L.P. Guan, L.M. Zhao, H.R. Piao and Z.S. Quan, Eur. J. Med. Chem., 43, 1216 (2008); doi:10.1016/j.ejmech.2007.08.006.

L.J. Guo, C.X. Wei, J.H. Jia, L.M. Zhao and Z.S. Quan, Eur. J. Med. Chem., 44, 954 (2009); doi:10.1016/j.ejmech.2008.07.010.

L.Q. Zhang, L.P. Guan, C.X. Wei, X.Q. Deng and Z.S. Quan, Chem. Pharm. Bull. (Tokyo), 58, 326 (2010); doi:10.1248/cpb.58.326.

M.X. Song, C.B. Zhang, X.Q. Deng, Z.G. Sun and Z.S. Quan, Lett. Drug Des. Discov., 8, 769 (2011); doi:10.2174/157018011796575962.

R.L. Krall, J.K. Penry, B.G. White, H.J. Kupferberg and E.A. Swinyard, Epilepsia, 19, 409 (1978); doi:10.1111/j.1528-1157.1978.tb04507.x.

R.J. Porter, J.J. Cereghino, G.D. Gladding, B.J. Hessie, H.J. Kupferberg, B. Scoville and B.G. White, Cleve. Clin. Quart., 51, 293 (1984); doi:10.3949/ccjm.51.2.293.

R.B. Gammill, J. Org. Chem., 46, 3340 (1981); doi:10.1021/jo00329a041.

Anticonvulsant Screening Project, Antiepileptic Drug Development Program. National Institute of Health, DHEW Publ (NIH), US, p. 78 (1978).

Issue

Vol. 26 No. 9 (2014): Vol 26 Issue 9

Synthesis and Anticonvulsant Activity Evaluation of 2-Phenyl-2H-benzo[e][1,3]oxazin-4(3H)-ones

Corresponding Author(s) : Guo-Hua Gong

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