Abstract
Michael addition of certain nucleophiles on α, β-unsaturated ketones 1 led to the formation of adducts2-7 as well as the reaction of arylidene derivatives with secondary amines afforded the amino compounds9 and11. Also, dialkylmalonates were treated with α-cyano cinnamide to afford13. On the other hand, double Michael cycloaddition of ethylcyanoacetate or tetrachlorophthalic anhydride to the suitable divinylketone were synthesized to produce15-17. Selected compounds (13 and6) were screened for muscle relaxant, anticonvulsant, and sedative activities using established pharmacological models. Their activities were compared with that of phenobarbital sodium taken as standard. Compound 6 was the most potent muscle relaxant while compounds13a and13c offered the highest anticonvulsant activity. Meanwhile compound13c showed the highest potentiation of phenobarbital induced sleep in mice.
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Aboal-Enein, M. N. and El-Azzouny, A. A., A Facile Synthesis of 2′,3′,7′,8′-Tetrahydro-7′-Aryl and Aralkylspiro[cycloalkyl 1,6′ (5′H)-imidazo[1,2-a] pyrazin]-5′-ones. A Heterocycle of Potential Analgesic Profile.Egypt. J. Chem., 31, 141 (1988).
Allen, L. E., Ferguson. H. C., and Kissel, J. W., Psychosedative Agents 2,8-(4-substituted-1-piperazinylalkyl)-8-azaspiro-[4.5]-decane-7,9-diones.J. Med. Chem., 15, 477 (1972).
Bloom, F., Neurotransmission and the Central nervous system. Inthe Pharmacological basis of therapeutics. Hardman J, Limbird L, Goodman A (eds). 10th Edition McGraw Hill Companies Jne. New York, USA (2001).
Bose, M., Dutta, D., Pathak, B., and Patra, B., Synthesis of some spiro[5.5] undecanes as possible Analgesic agents.J. Indian Chem. Soc., 62, 69 (1985).
Braulio, I, Alfredo, P., John, V., and Jairo, Q., Synthesis of 2,3-dihydropyrido and 2,3-dihydropyrimido[1,4] diazepines from triamino pyridine and triamino pyrimidine.J. Heterocyclic Chem., 34, 1555 (1997).
Carrol, F. A., Prespectives on structure and Mechanism. InOrganic Chemistry. Brooks/Cole Publishing Company 3rd Edition 645 (1988).
Collins, I., Moyes, C., Davey, W., Rowley, M., Bromidge, F., Quirk, K., Atack, J., McKernan, R., Thompson, S. A., Wafford, K., Dawson, G., Pike, A., Sohal, B., Tsou, N., Bull, R., and Castro, J., 3-Heteroaryl-2-pyridones: Benzodiazepine site ligands with functional selectivity for α2/α3-subtypes of human GABAA receptor-ion channels.J. Med. Chem., 45, 1887–1900 (2002).
De, A. U. and Pal, D., Possible Antineoplastic Agents 11.,J. Pharm. Sci., 66, 232 (1977).
Goehring, R. R, Greenwood, T. D., Nwokogus, G. C., Pisipati, J. S., Rogers, T. G., Wolfe, J. F. (Harvey W. Peters Res Cent. Study Parkinsons Dis. Disord. Cent. Nerv. Syst. Virginia Polytechnic Inst. And state Univ. Blacksburg. VA 24061 USA), Synthesis and anticonvulsant activity of 2-benzylglutarimides.J. Med. Chem., 33 (3), 926 (Eng) (1990). T.C.A. 112, 118615p (1990).
James, A. R., Gordon, D. J., Witold, F. K., Teanby, H. S., and John, W. P. (wellcome Foundation Ltd.), PCT Int. Appl. WO 95 01326 (Cl. Co7 C233/25), 12 Jan 1995, GB Appl. 93/13, 459, 30 Jun 1993; 60pp., Preparation of antiatherosclerotic diaryl compounds; T.C.A. 123, 143447V. (1995).
March, J., Advanced Organic Chemistry. John Willey and Sons, 4th Edition, 741 (2000).
Meyers, F. H, Jawetz, E., and GoldFien, A., Review of Medicinal Pharmaacology., Lange Medical Publications, Los Atlos, California; 5th Edition, 222 (1976).
Osman, A. N., Kandeel, M. M., Said, M. M., and Ahmed, E. M., Synthesis and anticonvulsant activity of some spiro compound derived from barbituric and thiobarbituric acids.Indian J. Chem., 35 B, 1073 (1996).
Reddy, D. B., Padmavathi, V., and Reddy, P. V. R., Cyclokexanone dicarboxylates as precursors for the synthesis of some spiropyrimidinetetrones and spiropyrazolidinetriones.Indian J. Chem., 31 B, 774 (1992).
Reddy, T. I. and Varma, R. S., Rare-earth (RE) exchanged nay zeolite promoted Knoevenagel condensation.Tetrahedron Lett., 38, 1721 (1997).
Sergio, M., Tiziano, B., Enzo, B., Metlide, B. (Farmitalia Carlo Erba S.R.I.) Eur. Pat. Appl. Ep 449, 346 (Cl CO7D 457/02), 02 Oct 1991. GB Appl. 9016, 722, 27 Mar 1990; 9 pp.; preparation of [(4.piperidinyl)akyl] ergolines as antiparkinson agents; T.C.A. 116, 21303e (1992).
Sykes, P., A guidebook to Mechanism in Organic Chemistry Long mon London and New York,New York, 5th Edition, 198 (1985).
Villar, R., Laguna, M. R., Calleja, J. M., and Cadavid, I., Effect of Kseletonema statum extracts on the central nervous system.Planta Med., 38, 398 (1992).
Vogel, A. G. and Vogel, W. H., Drug Discovery and Evaluation, Pharmacological Assay, Spring, Berlin 260 (1997).
Vollhardt, K. P. C., Organic Chemistry., W. H. Freeman and Company New York 3rd Edition, 1048 (1999).
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Said, M.M., Ahmed, A.A.E. & El-Alfy, A.T. Synthesis and pharmacological screening for muscle relaxant, anticonvulsant, and sedative activities of certain Organic compounds produced by Michael addition. Arch Pharm Res 27, 1194–1201 (2004). https://doi.org/10.1007/BF02975880
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DOI: https://doi.org/10.1007/BF02975880