Synthesis and anticonvulsant activity of enaminones - Part 7. Synthesis and anticonvulsant evaluation of ethyl 4-[(substituted phenyl)amino]-6-methyl-2-oxocyclohex-3-ene-1-carboxylates and their corresponding 5-methylcyclohex-2-enone derivatives

European Journal of Medicinal Chemistry

Volumn 38, Issue 1, 2003, Pages 49-64

  Eddington, Natalie D ^a   Cox, Donna S ^a,e   Khurana, Manoj ^a   Salama, Noha N ^a   Stables, James P ^b   Harrison, Sylvia J ^c   Negussie, Abraham ^c   Taylor, Robert S ^c   Tran, Uy Q ^c   Moore, Jacqueline A ^c   Barrow, Judith C ^d   Scott, K R ^c  

^a UNIVERSITY OF MARYLAND SCHOOL OF PHARMACY   (United States)

^b NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE   (United States)

^c HOWARD UNIVERSITY   (United States)

^d Howard University   (United States)

^e DUPONT COMPANY   (United States)

Author keywords

Anticonvulsant activity; Enaminones; LC MS analysis; Maximal electroshock seizure test; Structure activity relationship

Indexed keywords

3 [N (3 BROMOPHENYL)AMINO] 5 METHYL 2 CYCLOHEXENONE; 3 [N (3 CHLOROPHENYL)AMINO] 5 METHYL 2 CYCLOHEXENONE; 3 [N (3 CYANOPHENYL)AMINO] 5 METHYL 2 CYCLOHEXENONE; 3 [N (3 FLUOROPHENYL)AMINO] 5 METHYL 2 CYCLOHEXENONE; 3 [N (3 IODOPHENYL)AMINO] 5 METHYL 2 CYCLOHEXENONE; 3 [N (3 METHOXYPHENYL)AMINO] 5 METHYL 2 CYCLOHEXENONE; 3 [N (3 NITROPHENYL)AMINO] 5 METHYL 2 CYCLOHEXENONE; 3 [N (3 TOLYL)AMINO] 5 METHYL 2 CYCLOHEXENONE; 3 [N (3 TRIFLUOROMETHOXYPHENYL)AMINO] 5 METHYL 2 CYCLOHEXENONE; 3 [N (3 TRIFLUOROMETHYLPHENYL)AMINO] 5 METHYL 2 CYCLOHEXENONE; 3 [N (4 BROMOPHENYL)AMINO] 5 METHYL 2 CYCLOHEXENONE; 3 [N (4 CYANOPHENYL)AMINO] 5 METHYL 2 CYCLOHEXENONE; 3 [N (4 FLUOROPHENYL)AMINO] 5 METHYL 2 CYCLOHEXENONE; 3 [N (4 IODOPHENYL)AMINO] 5 METHYL 2 CYCLOHEXENONE; 3 [N (4 NITROPHENYL)AMINO] 5 METHYL 2 CYCLOHEXENONE; 3 [N (4 TRIFLUOROMETHYLPHENYL)AMINO] 5 METHYL 2 CYCLOHEXENONE; 3 N [(4 TOLYL)AMINO] 5 METHYL 2 CYCLOHEXENONE; 3 N [(PHENYL)AMINO] 5 METHYL 2 CYCLOHEXENONE; ANTICONVULSIVE AGENT; CYCLOHEXENE DERIVATIVE; ENAMINE; ESTER DERIVATIVE; ETHYL 4 [(4 CHLOROPHENYL)AMINO] 6 METHYL 2 OXOCYCLOHEX 3 ENE CARBOXYLATE; ETHYL 4 [(4 CYANOPHENYL)AMINO] 6 METHYL 2 OXOCYCLOHEX 3 ENE 1 CARBOXYLATE; KETONE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTICONVULSANT ACTIVITY; ARTICLE; BRAIN; CONTROLLED STUDY; DRUG DISTRIBUTION; DRUG METABOLISM; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; ELECTRIC SHOCK; LIQUID CHROMATOGRAPHY; MALE; MASS SPECTROMETRY; NONHUMAN; RAT; SEIZURE; URINE;

ANIMALS; ANTICONVULSANTS; BRAIN CHEMISTRY; CYCLOHEXANECARBOXYLIC ACIDS; CYCLOHEXANONES; ELECTROSHOCK; MICE; MODELS, CHEMICAL; MOLECULAR STRUCTURE; RATS; RATS, SPRAGUE-DAWLEY; SEIZURES; SODIUM CHANNELS; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0037367811     PISSN: 02235234     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0223-5234(02)00006-5     Document Type: Article

References (43)

1. J.J. Coatsworth, NINDS Monograph No. 12 HEW Publication No. (NIH) 73-51, US Government Printing Office, 1971.
2. Edafiogho I.O., Hinko C.N., Chang H., Moore J.A., Mulzac D., Nicholson J.M., Scott K.R. J. Med. Chem. 35:1992;2798-2805.
3. Mulzac D., Scott K.R. Epilepsia. 34:1993;1141-1146.
4. Nicholson J.M., Edafiogho I.O., Moore J.A., Farrar V.A., Scott K.R. J. Pharm. Sci. 83:1994;76-78.
5. Edafiogho I.O., Moore J.A., Farrar V.A., Nicholson J.M., Scott K.R. J. Pharm. Sci. 83:1994;79-84.
6. Edafiogho I.O., Moore J.A., Alexander M.S., Scott K.R. J. Pharm. Sci. 83:1994;1155-1170.
7. Edafiogho I.O., Alexander M.S., Moore J.A., Farrar V.A., Scott K.R. Curr. Med. Chem. 1:1994;159-175.
8. Scott K.R., Edafiogho I.O., Richardson E.L., Farrar V.A., Moore J.A., Tietz E.I., Hinko C.N., Chang H., El-Assadi A., Nicholson J.M. J. Med. Chem. 36:1993;1947-1955.
9. Scott K.R., Rankin G.O., Stables J.P., Alexander M.S., Edafiogho I.O., Farrar V.A., Kolen K.R., Moore J.A., Sims L.D., Tonnu A.D. J. Med. Chem. 38:1995;4033-4043.
10. Laws M.L., Roberts R.R., Nicholson J.M., Butcher R., Stables J.P., Goodwin A.M., Smith C., Scott K.R. Bioorg. Med. Chem. 6:1998;2289-2299.
11. Foster J.E., Nicholson J.M., Butcher R., Stables J.P., Edafiogho I.O., Goodwin A.M., Henson M.C., Smith C.A., Scott K.R. Bioorg. Med. Chem. 7:1999;2415-2425.
12. Eddington N.D., Cox D.S., Roberts R.R., Stables J.P., Powell C.B., Scott K.R. Curr. Med. Chem. 7:2000;417-436.
13. Cox D.S., Du J., Scott K.R., Gao H., Eddington N.E. J. Chromatogr. Sect. B. 749:2000;191-196.
14. Cox D.S., Scott K.R., Gao H., Raje S., Eddington N.D. J. Pharm. Sci. 90:2001;1540-1552.
15. Cox D.S., Gao H., Raje S., Scott K.R., Eddington N.D. Eur. J. Pharm. Biopharm. 52:2001;145-150.
16. Eddington N.D., Cox D.S., Roberts R.R., Butcher R.J., Edafiogho I.O., Stables J.P., Cooke N., Goodwin A.M., Smith C.A., Scott K.R. Eur. J. Med. Chem. 37:2002;635-648.
17. Cox D.S., Scott K.R., Gao H., Eddington N.D. J. Pharmacol. Exp. Ther. 302:2002;1096-1104.
18. Friary R.J., Gilligan J.M., Szajewski R.P., Falci K.J., Franck R.W. J. Org. Chem. 38:1973;3487-3491.
19. Stables J.P., Kupferberg H.J. The NIH anticonvulsant drug development (ADD) program: preclinical anticonvulsant screening project. Avanzini G., Tanganelli P., Avoli M. Molecular and Cellular Targets for Anti-epileptic Drugs. 1997;191-198 John Libbey and Co.
20. Krall R.L., Penry J.K., White B.G., Kupferberg H.J., Swinyard E.A. Epilepsia. 19:1978;409-428.
21. Porter R.J., Cereghino J.J., Gladding G.D., Hessie B.J., Kupferberg H.J., Scoville B., White G.G. Cleveland Clin. Q. 51:1984;293-305.
22. Piredda S.G., Woodhead J.H., Swinyard E.A. J. Pharmacol. Exp. Ther. 232:1985;741-745.
23. Edafiogho I.O., Abdel-Hamid M.E., Hamza H., Scott K.R. J. Liq. Chromatogr. Relat. Technol. 24:2001;565-577.
24. MACLOGP Program, Version 4.0 BioByte Corp., Claremont, CA 91711, USA.
25. Willow M., Kuenzel E.A., Catterall W.A. Mol. Pharmacol. 25:1984;228-234.
26. Zhu Y., Im W.B., Lewis R.A., VonVoigtlander P.F. Br. J. Pharmacol. 106:1992;49-54.
27. Natsuki N., Quandt F.N., Eick R.E., Yeh J.Z. J. Pharmacol. Exp. Ther. 228:1948;523-530.
28. Benes J., Parada A., Figueiredo A.A., Alves P.C., Freitas A.P., Learmonth D.A., Cunha R.A., Garrett J., Soares-da-Silva P. J. Med. Chem. 42:1999;2582-2587.
29. Vamecq J., Bac P., Herrenknecht C., Maurois P., Delcourt P., Stables J.P. J. Med. Chem. 43:2000;1311-1319.
30. Oliver A.P., Hoffer B.J., Wyatt R.J. Epilepsia. 18:1977;543-548.
31. Piredda S., Yonekawa W.D., Whittingham T.S., Kupferberg H.J. Epilepsia. 26:1985;167-174.
32. Lothman E.W., Salerno R.A., Perlin J.B., Kaiser D.L. Epilepsy Res. 2:1988;367-379.
33. Kupferberg H.J., Stables J.P. Mechanisms of action revisited: drug discovery, testing and clinical prediction. Stefan H., Kramer G., Mamoli B. Challenge in Epilepsy - New Anticonvulsant Drugs. 1998;7-27 Blackwell Science Ltd.
34. Craig P.N. J. Med. Chem. 14:1971;680-684.
35. Craig P.N. J. Med. Chem. 14:1971;144-149.
36. J.P. Stables, personal communication.
37. Mecozzi S., West A.P. Jr., Dougherty D.A. Proc. Natl. Acad. Sci. USA. 93:1996;10566-10571.
38. Dougherty D.A. Science. 271:1996;163-168.
39. Dougherty D.A., Stauffer D.A. Science. 250:1990;1558-1560.
40. M.E. Abdel-Hamid, I.O. Edafiogho, K.R. Scott, J. Pharm. Biochem. Anal. 30 (2002) 1001-1011.
41. Hamill O.P., Marty A., Neher E., Sakmann B., Sigworth F.J. Pfluger's Arch. 391:1981;85-100.
42. Lothman E.W., Williamson J.M. Brain Res. 649:1994;71-84.
43. Guide for the Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources, National Research Council, 1986, NIH Publication No. 86-23.