Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
권호 표지
DOI QR코드

DOI QR Code

Synthesis of 6-Alkyloxyl-3,4-dihydro-2(1H)-quinoliones and Their Anticonvulsant Activities

  • Quan, Zhe Shan (College of Pharmacy, Yanbian University) ;
  • Wang, Jun-Min (College of Pharmacy, Yanbian University) ;
  • Rho, Jung-Rae (Department of Marine Information Science, Kunsan National University) ;
  • Kwak, Kyung-Chell (Department of Bionanochemistry and Basic Sciences Research Institute, Wonkwang University / Medicinal Resources Research Center of Wonkwang University) ;
  • Kang, Hee-Cheol (Department of Bionanochemistry and Basic Sciences Research Institute, Wonkwang University / Medicinal Resources Research Center of Wonkwang University) ;
  • Jun, Chang-Soo (Department of Bionanochemistry and Basic Sciences Research Institute, Wonkwang University / Medicinal Resources Research Center of Wonkwang University) ;
  • Chai, Kyu-Yun (Department of Bionanochemistry and Basic Sciences Research Institute, Wonkwang University / Medicinal Resources Research Center of Wonkwang University)
  • Published : 2005.11.20
Download PDF
⟨ Previous Next ⟩

Abstract

A series of 6-alkyloxyl-3,4-dihydro-2(1H)-quinoliones (5a-5n) were synthesized through nitration, reduction, diazotization, hydrolysis and alkylation from 3,4-dihydro-2(1H)-quinolione. Their structures were characterized by IR, $^1H$-NMR and MS. The anticonvulsant activity was evaluated by the Maximal electroshock test (MES) and the subcutaneous pentylenetetrazole (Metrazole) test (sc-Met). The neurotoxicity was measured by the Rotarod test (Tox). The result showed that 6-hexyloxy-3,4-dihydro-2 (1H)-quinolinone (5c) was potent in anti-MES and anti-scMet test with $ED_{50}$ of 24.0 mg/kg and 21.2 mg/kg, respectively, albeit its $TD_{50}$ (67.6 mg/kg) revealed the high neurotoxicity. 6-Benzyloxy-3,4-dihydro-2(1H)-quinolinone (5f) was less effective against MES induced seizure with $ED_{50}$ of 29.6 mg/kg, but no neurotoxicity was observed even under 300 mg/kg. Its Protective index (PI) was greater than 10 preferable to Phenytoin, Carbamazepin, Phenobarbital and Valproate.

Keywords

References

  1. Joseph, B.; Darro, F.; Behard, A.; Lesur, B.; Collignon, F.; Decaestecker, C.; Frydman, A.; Guillaumet, G.; Kiss, R. J. Med. Chem. 2002, 45, 2543-2555 https://doi.org/10.1021/jm010978m
  2. Xiao, Z.; Waters, N. C.; Woodard, C. L.; Li, Z.; Li, P. K. Bioorg. Med. Chem. Lett. 2001, 11, 2875-2878 https://doi.org/10.1016/S0960-894X(01)00578-9
  3. Nishi, T.; Kimura, Y.; Nakagawa, K. Yakugaku. Zasshi. 2000, 120, 1247-1260
  4. Oshiro, Y.; Sakurai, Y.; Sato, S.; Kurahashi, N.; Tanaka, T.; Kikuchi, T.; Tottori, K.; Uwahodo, Y.; Miwa, T.; Nishi, T. J. Med. Chem. 2000, 43, 177-189 https://doi.org/10.1021/jm980333v
  5. Otsubo, K.; Morita, S.; Uchida, M.; Yamasaki, K.; Kanbe, T.; Shimizu, T. Chem. Pharm. Bull. 1991, 39, 2906-2909 https://doi.org/10.1248/cpb.39.2906
  6. Banno, K.; Fujioka, T.; Kikuchi, T.; Oshiro, Y.; Hiyama, T.; Nakagawa, K. Chem. Pharm. Bull. 1988, 36, 4377-4388 https://doi.org/10.1248/cpb.36.4377
  7. Bell, A. S.; Campbell, S. F.; Roberts, D. A.; Ruddock, K. S. J. Med. Chem. 1989, 32, 2042-2049 https://doi.org/10.1021/jm00129a005
  8. Piao, H. R.; Quan, Z. S.; Xu, M. X.; Deng, D. W. Chin. J. Med. Chem. 1999, 9, 79-83 https://doi.org/10.1021/jm00319a021
  9. Wu, C. X.; Dai, L. Y.; Chen, Y. Q.; Weng, Z. X. . 2003, 61, 337-339
  10. Krall, R. L.; Penry, J. K.; White, B. G..; Kupferberg, H. J.; Swinyard, E. A. Epilepsia. 1978, 19, 409-428 https://doi.org/10.1111/j.1528-1157.1978.tb04507.x
  11. Porter, R. J.; Cereghino, J. J.; Gladding, G. D.; Hessie, B. J.; Kupferberg, H. J.; Scoville, B.; White, B. G.. Cleve. Clin. Q 1984, 51, 293-305 https://doi.org/10.3949/ccjm.51.2.293
  12. Ucar, H.; Van derpoorten, K.; Cacciaguerra, S.; Spampinato, S.; Stables, J. P.; Depovere, P.; Isa, M.; Masereel, B.; Delarge, J.; Poupaert, J. H. J. Med. Chem. 1998, 41, 1138-1145 https://doi.org/10.1021/jm970682+

Cited by

  1. Combinatorial Library Synthesis of N-arylquinoline Derivatives in Aqueous Medium vol.60, pp.3, 2012, https://doi.org/10.1002/jccs.201200359
  2. Synthesis and anticonvulsant activity evaluation of 7-alkoxy-2,4-dihydro-1H-benzo[b][1,2,4]triazolo[4,3-d][1,4]thiazin-1-ones in various murine experimental seizure models vol.23, pp.4, 2014, https://doi.org/10.1007/s00044-013-0778-y
  3. Synthesis of Novel 2-Oxoquinoline Derivatives via Ugi-Four-Component-Heck Reaction vol.52, pp.2, 2014, https://doi.org/10.1002/jhet.2053
  4. Synthesis of 8-alkoxy-4,5-dihydro-[1,2,4]triazole[4,3-a]quinoline-1-ones and evaluation of their anticonvulsant properties vol.29, pp.12, 2006, https://doi.org/10.1007/BF02969295
  5. Synthesis of 2-Substituted-7-heptyloxy-4,5-dihydro-[1,2,4]-triazolo[4,3-a]quinolin-1(2H)-ones with Anticonvulsant Activity vol.340, pp.9, 2007, https://doi.org/10.1002/ardp.200700106
  6. Synthesis and Anti-inflammatory Activity Evaluation of Novel 7-Alkoxy-1-amino-4,5-dihydro[1,2,4]triazole[4,3-a]quinolines vol.341, pp.5, 2008, https://doi.org/10.1002/ardp.200700182
  7. Synthesis and anticonvulsant evaluation of 3-substituted-4-(4-hexyloxyphenyl)-4H-1,2,4-triazoles vol.18, pp.1, 2009, https://doi.org/10.1007/s00044-008-9106-3
  8. ]Phthalazines vol.73, pp.3, 2009, https://doi.org/10.1111/j.1747-0285.2009.00776.x
  9. ]quinazolines vol.342, pp.11, 2009, https://doi.org/10.1002/ardp.200900119
  10. Synthesis and Anticonvulsant Activity of Some 7-Alkoxy-2H-1,4-benzothiazin-3(4H)-ones and 7-Alkoxy-4H-[1,2,4]triazolo[4,3-d]benzo[b][1,4]thiazines vol.58, pp.3, 2010, https://doi.org/10.1248/cpb.58.326
  11. Synthesis and anticonvulsant activity of 1-formamide-triazolo[4,3-a]quinoline derivatives vol.33, pp.5, 2010, https://doi.org/10.1007/s12272-010-0502-0
  12. Synthesis of 6-Alkyloxyl-3,4-dihydro-2(1H)-quinolinones and Their Anticonvulsant Activities. vol.37, pp.10, 2005, https://doi.org/10.1002/chin.200610236
  13. Synthesis and Studies on Anticonvulsant and Antidepressant Activities of 5-Alkoxy-tetrazolo[1,5-a]quinolines vol.31, pp.2, 2010, https://doi.org/10.5012/bkcs.2010.31.02.447
  14. Synthesis and anticonvulsant activity of a new 6-alkoxy-[1,2,4]triazolo[4,3-b]pyridazine vol.45, pp.5, 2005, https://doi.org/10.1016/j.ejmech.2009.12.077
  15. Ruthenium-Catalyzed Intramolecular Arene C(sp2)-H Amidation for Synthesis of 3,4-Dihydroquinolin-2(1H)-ones vol.23, pp.9, 2005, https://doi.org/10.1021/acs.orglett.1c00781