Convenient Synthesis and Biological Activity of 4-Aminomethylene 1-phenylpyrazolidine-3,5-diones

Eman A. Ahmed

Chemistry Department, Faculty of Science, Sohag University, 82524 Sohag, Egypt. E-mail: abdala_15@yahoo.com. Tel.: +20934601159.

Received April 1^st, 2015; ]]> Accepted August 3^rd, 2015.

Abstract

Reaction of (Z)-4-((dmethylamino)methylene)-1-phenylpyrazolidine-3,5-dione (1) with different nucleophiles is described. Treatment of enaminone 1 with phenylhydrazine led to 3-oxo-W,2-diphenyl-2,3-dihydro-1H-pyrazole-4-carbohydrazide 7. New enaminone derivatives 2-6 and 12-14 were conveniently obtained in high yields via nucleophilic substitution of the dimethylamino group in enaminone 1 when reacted with o-aminophenol, o-aminothiophenol, ethanolamine, cysteamine hydrochloride, piperidine, morpholine, 2-aminopyridine and glycine. Reaction of enaminone 1 with diaza-nucleophiles, such as hydrazine hydrate, ethylenediamine and o-phenylenediamine, afforded the corresponding bis-enaminones 9-11. Anti-inflammatory and antimicrobial activities of some new products were evaluated. Compounds 1, 2, 4, 7, 12a, and 12b showed high anti-inflammatory activity compared with indomethacin as the reference, while the highest antimicrobial effect was observed in the case of compound 3.

Key words: pyrazolidine-3,5-diones, enaminones, nucleophiles, anti-inflammatory activity, antimicrobial activity.

Resumen

Se describe la reacción de (Z)- 1-fenil-4-((dimetilamino) metilen)pirazolidin-3,5-diona (1) con diferentes nucleófilos. El tratamiento de la enaminona 1 con fenilhidrazina condujo a la N', 2-difenil-2,3-dihidro-3-oxo-1H-pirazol-4-carbohidrazida 7. Los nuevos derivados enaminónicos 2-6 y 12-14 se obtuvieron convenientemente en elevados rendimientos vía sustitución nucleofílica del grupo dimetilamino en la enaminona 1 cuando reaccionó con o-aminofenol, o-aminotiofenol, etanolamina, clorhidrato de cisteamina, piperidina, morfolina, 2-aminopiridina y glicina. La reacción de 1 con diaza-nucleófilos, tales como hidrato de hidrazina, etilendiamina y o-fenildiamina, proporcionó las bis-enaminonas correspondientes 9-11. Se evaluó la actividad anti-inflamatoria y antimicrobiana de algunos productos nuevos. Los compuestos 1, 2, 4, 7, 12a y 12b mostraron elevada actividad anti-inflamatoria en comparación a la indometacina como compuesto de referencia, mientras que se observó la más elevada actividad antimicrobiana para el compuesto 3.

Palabras clave: pirazolidin-3,5-dionas, enaminonas, nucleófilos, actividad anti-inflamatoria, actividad antimicrobiana.

References

1. Singh, K.; Singh, J.; Singh, H. Tetrahedron 1998, 54, 935-942.         [ Links ]

2. Shawali, A. S.; Haboub, A. J. M. J. Chem. Res. 2011, 35, 341-345.         [ Links ]

3. Al-Awadi, N. A.; Ibrahim, M. R.; Elnagdi, M. H.; John, E.; Ibrahim, Y. A. Beilstein J. Org. Chem. 2012, 8, 441-447.         [ Links ]

4. Domínguez, E.; Ibeas, E.; de Maigorta, E. M.; Palacios, J. K.; SanMartin, R. A. J. Org. Chem. 1996, 61, 5435-5439.         [ Links ]

5. Nikolovaa, S.; Kochovskaa, E.; Ivanov, I. Synth. Commun. 2013, 43, 326-336.         [ Links ]

6. Khodairy, A. Synth. Commun. 2011, 41, 612-621.         [ Links ]

7. Nagaraju, V.; Purnachander, D.; Rao Mangina, N. S. V. M.; Suresh, S.; Sridhar, B.; Karunakar, G. V. Org. Biomol. Chem. 2015, 13, 3011-3023.         [ Links ]

8. Khurana, M.; Salama, N. N.; Scott, K. R., Nemieboka, N. N.; Bauer, K. S. Jr.; Eddington, N. D. Biopharm. Drug Dispos. 2003, 24, 397-407.         [ Links ]

9. Thumar, N. J.; Patel, M. P. Saudi Pharm J. 2011, 19, 75-83.         [ Links ]

10. Michael, J. P.; Koning, C. B.; Hosken, G. D.; Stanbury, T. V. Tetrahedron 2001, 57, 9635-9648.         [ Links ]

11. Jackson, P. L.; Hanson, C. D.; Farrell, A. K.; Butcher, R. J.; Stables, J. P.; Eddington, N. D.; Scott, R. K. Eur. J. Med. Chem. 2012, 5, 42-51.         [ Links ]

12. Riyadh, S. M. Molecules 2011, 16, 1834-1853.         [ Links ]

13. El-Shennawy, A. M.; Mohamed, A. H.; Abass, M. Medscape Gen. Med. J. 2007, 9, 15-33.         [ Links ]

14. Naringrekar, V. H.; Stella, V. J. J. Pharm. Sci. 1990, 79, 138-146.         [ Links ]

15. El-Deeb, I. M.; Lee, S. H. Bioorg. Med. Chem. 2010, 18, 3961-3973.         [ Links ]

16. Rashad, A. E.; Hegab, M. I.; Abdel-Megeid, R. E.; Micky, J. A.; Abdel-Megeid, F. M. E. Bioorg. Med. Chem. 2008, 16, 7102-7106.         [ Links ]

17. El-Hashim, A.; Yousefi, S.; Edafiogho, I.; Raghupathy, R.; Yousif, M.; Simon, H. Eur. J. Pharm. 2010, 632, 73-78.         [ Links ]

18. Kolle, U.; Kolb, B.; Mannschreck, A. Chem. Ber. 1980, 113, 2545-2565.         [ Links ]

19. Crystallographic data have been deposited at the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 964084. Akkurt, M.; Mohamed, S. K.; Elremaily, M. A. A.; Ahmed, E. A.; Albayati, M. R. Acta Crystallogr. E 2013, 69, o1408-o1409.         [ Links ]

20. Crystallographic data have been deposited at the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 1005600. Mague, J. T.; Mohamed, S. K.; Akkurt, M.; Ahmed, E. A.; Albayati, M. R. Acta Crystallogr. E 2014, 70, o819-o820.         [ Links ]

21. Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 270-283.         [ Links ]

22. Janoschek, R. Pure Appl. Chem. 2001, 73, 1521-1553.         [ Links ]

23. Crystallographic data have been deposited at the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 1015152. Mohamed, S. K.; Akkurt, M.; Mague, J. T.; Ahmed, E. A. and Albayati, M. R. Acta Crystallogr. E 2014, 70, o938-o939.         [ Links ]

24. Kataoka, T.; Teraoka, J.; Sakoda, A.; Nishiyama, Y.; Yamato, K.; Monden, M., Ishimori, Y; Nomura, T.; Taguc, T., Yamaoka, K. Inflammation 2012, 35, 713-722.         [ Links ]

25. Winter, C. A.; Risley, E. A.; Nuss, G. W. Experiment. Biol. Med. 1962, 111, 544-547.         [ Links ]