Xian-Yu SUN, Kyu-Yun CHI, Guan-Rong TIAN, Li-Ping GUAN, Zhe-Shan QUAN

The synthesis and anticonvulsant activity of 1-substituted-7-methoxy-1,2,4,-triazolo [4, 3-a] quinoline

A new series of 1-substituted-7-methoxy-5-phenyl-1,2,4-triazolo[4,3-a]quinolines were synthesized using ethyl-3-oxo-3-phenylpropanoate and 4-methoxybenzenamine as the starting material. Their anticonvulsant activity was evaluated by the maximal electroshock (MES) test and 7-methoxy-5-phenyl-1,2,4-triazolo[4,3-a]quinoline (4a) was identified as the most potent compound, with an $ED_{50}$ value of 9.2 mg $kg^{−1}$, which is comparable to the reference drug phenytoin ($ED_{50}$ = 9.9 mg $kg^{−1}$). To explore the possible mechanism of its anticonvulsant activity, compound 4a was tested with the rotarod neurotoxicity test, pentylenetetrazole (sc-PTZ) test, and isoniazid test. Compound 4a had a higher protective index (PI = $TD_{50}/ED_{50}$) value (16.6) than phenytoin (PI = 7.0), and it antagonized pentylenetetrazole- and isoniazid-induced seizures with an ED50 of 21.1 mg $kg^{−1}$ and 83.3 mg $kg^{−1}$, respectively.

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1. W. Loscher, Eur. J. Pharmacol. 1, 1-13 (1998).
2. I. E. Leppik, Epilepsia. 35 (S4), 29-40 (1994).
3. Y. A. Al-Soud, N. A. Al-Masoudi and Ael-R. Ferwanah, Bioorg. Med. Chem. 11, 1701-1708 (2003).
4. L. P. Guan, Q. H. Jin, G. R. Tian, K. Y. Chai and Z. S. Quan, J. Pharm. Pharm. Sc. 3, 254-262 (2007).
5. R. J. Krall, J. K. Penry, B. G. White and H. J. Kupferberg, Epilepsia. 19, 409-428 (1978).
6. R. J. Poter, J. J. Cereghino, G. D. Gladding, B. J. Hessie, H. J. Kupferberg and B. Scoville, Clev. Clin. J. Med. 51, 293-305 (1984).
7. M. Geurts, J. H. Poupaert, G. K. Scriba and D. M. Lambert, J. Med. Chem. 41, 24-30 (1998).
8. R. Bernasconi, M. Klein, P. Martin, P. Christen, T. Hafner, C. Portet and M. Schmutz, J. Neural. Transm. 72, 213-233 (1988).
9. K. Hino, K. Kawashima, M. Oka, H. Uno, and J. I. Matsumoto, Chem. Pharm. Bull. 1,190-192 (1989).
10. B. Bouteau, J. C. Lancelot and M. Robba, J. Heterocycl. Chem. 6, 1649-1651 (1990).
11. D. B. Moran, G. O. Morton and J. D. Albright, J. Heterocycl. Chem. 23, 1071-1077 (1986).
12. R. Okada and H. Negishi, Brain Res. 480, 383-387 (1989).
13. R.W. Olsen, J. Neurochem. 27, 1-3 (1981).
14. K. Gale, Epelepsia. 33, S3-S12 (1992).