SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL ACTIVITY OF NOVEL PYRAZOLO[3,4-b]PYRIDINES AND THEIR SPIRO-HETEROCYCLIC DERIVATIVES
DOI:
https://doi.org/10.24297/jac.v10i7.6802Keywords:
Pyrazolo[3,4-b]pyridine, Chalcones, Heterocyles, Spiroindolylpyrazolopyridine, AntimicrobialAbstract
The present work describes the synthesis of a novel series of heterocyclic moieties derived from 5-acetylpyrazolo[3,4-b]pyridine (1). The formation of chalcones (2a-d) was utilized to synthesize pyrazoline, isoxazoline and pyrimidine derivatives (3-10). Thiosemicarbazone and semicarbazone (11, 17) were utilized to synthesize other new triazolethiones, thiadiazole and selenadiazole derivatives (11-19). Some new spiro derivatives (22-25) were synthesized by the reaction of chalcone (21) of 1 and isatine with hydrazines, hydroxyl amines and thiourea. Also, The reaction of 1 with cyanoacetyl hydrazine gave the hydrazide-hydrazone derivative 26, which was allowed to react with aromatic aldehydes and α-cyanocinnamonitrile to afford coumarine and substituted pyridine derivatives (28, 29). The structures of all the new compounds have been established on the basis of their analytical and spectral data. Twenty two of the synthesized compounds were also evaluated for their antibacterial and antifungal activity against various strains of bacteria and fungi and most are found to possess promising antimicrobial activity when compared with Chloramphenicol and Clotrimazole
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[13] Abdel-Aziz, H.A., Saleh, T.S., and El-Zahabi, H.A.S. Arch. Pharm. 2010, 343, 24-30. Facile Synthesis and In-Vitro Antitumor Activity of Some Pyrazolo[3,4-b]pyridines and Pyrazolo[1,5-a]pyrimidines Linked to a Thiazolo[3,2 a]benzimidazole Moiety.
[14] Cunico, W., Cechinel, C.A., Bonacorso, H.G., Martins, M.A., Zanatta, N., de Souza, M.V., Freitas, I.O., Soares, R.P., and Krettli, A.U. Bioorg. Med. Chem. Lett. 2006, 16, 649-653. Antimalarial activity of 4-(5-trifluoromethyl-1H pyrazol-1-yl)-chloroquine analogues
[15] El-Emary, T.I., Kamal El-Dean, A.M., and El-Kashef, H.S. II Farmaco, 1998, 53, 383-388. Facile synthesis of some new pyrazolo [3,4-b] pyrazines and their antifungal activity.
[16] El-Kashef, H.S., El-Emary, T.I., Gasquet, M., Timon-David, P., Maldonado, J., and Vanelle, P. Pharmazie, 2000, 55, 572-576. New pyrazolo[3,4-b]pyrazines: Synthesis and biological activity.
[17] El-Emary, T.I., and Abdel-Mohsen, S.A. Molecules, 2012, 17, 14464-14483. Multi-Component One-Pot Synthesis and Antimicrobial Activities of 3-Methyl- 1,4-diphenyl-7-thioxo-4,6,8,9-tetrahydropyrazolo[5,4-b]pyrimidino[5,4- e]pyridine-5-one and Related Derivatives.
[18] Bernardino, A.M.R., Rolim, A.M., and Castro, H.C. Bioorg. Med. Chem . 2006, 14, 5765–5770. Design, synthesis, SAR, and biological evaluation of new (phenylamino)pyrazolo[2,3-b]pyridine4- derivativesâ€.
[19] Wust, F., Kniess, T., Kretzschmar, M., and Bergmann, R. Bioorg. Med. Chem. Lett. 2005, 15,1303-1306. Synthesis and biodistribution of a 18F-labelled corticosteroid as ligand for mapping brain glucocorticoid receptors by means of PET.
[20] Helosia, D.M., Aurea, E., Alice, M.B., Marilene, C.C., and Leonor, L.L. J. Med. Chem. 2004, 47, 5427-5432. Antileishmanial Pyrazolopyridine Derivatives:Synthesis and Structure−Activity Relationship Analysis.
[21] Yu, G., Mason, H.J., Wu, X., Wang, J., Chong, S., Dorough, G., Henwood, A., Pongrac, R., Seliger, L., He, B., Normandin, D., Adam, L., Krupinski, J., and Macor, J.E. J. Med. Chem. 2001, 44, 1025-1027. Substituted pyrazolopyridines as potent and selective PDE5 inhibitors: potential agents for treatment of erectile dysfunction.
[22] El-Kashef, H.S. and El-Emary, T.I. J. Chem. Res. Synop. 1998, 20-21. Polycyclic Pyrazoles: Routes to New Pyrazoloazines.
[23] El-Emary, T.I., and Bakhite, E.A. Pharmazie, 1999, 54, 106-111. Synthesis and biological screening of new 1,3-diphenylpyrazoles with different heterocyclic moieties at position-4.
[24] El-Emary, T.I., Al-Muaikel, N., and Moustafa, O.S. Phosphorus Sulfur Silicon Relat. Elem.2002, 177, 195-210. Synthesis and Antimicrobial Activity of some New Heterocycles Based on 3-Methyl-1-Phenyl-5-Benzene Sulfonamido Pyrazole.
[25] El-Emary, T.I., Khalil, A., El-Hag, G.A., and El-Adasy, M. A. Phosphorus Sulfur Silicon Relat. Elem. 2005, 180, 19-30. A Facile Synthesis of Some New Thiazolo[3, 2]pyridines Containing Pyrazolyl Moiety and Their Antimicrobial Activity.
[26] Haeufel ,J., and Breitmeir, E. Angew. Chem. Int. Ed. Engl. 1974, 13: 604-609. Synthesis of Pyrazolo Heteroaromatic Compounds by Means of 5-Amino-3-methyl-1-phenylpyrazole-4-carbaldehyde.
[27] El-Emary, T.I. j. Chin. Chem. Soc.2007, 54, 507-518. Synthesis of Newly Substituted Pyrazoles and Substituted Pyrazolo[3,4-b]pyridines Based on 5-Amino-3-methyl-1-phenylpyrazole.
[28] Haythem, A.S., Ibrahim, M. M., Amal, G.A., and Mohammad, S.M. Monatsh. Chem. 2010, 141,471–478.Synthesis and antimicrobial activity of new 1,2,4-triazole-3-thiol metronidazole derivatives.
[29] Saravanan, S., Nithya, A., and Muthusubramanian, S. J. heterocycl. Chem. 2006, 43, 149-155. Synthesis and characterization of 4-aryl-5-(1-aryl-2-methyl-2-nitropropyl)-1,2,3-selenadiazoles .
[30] Sondhi, S.M., Dinodia, M., and Kumar, .A. Bioorg. Med. Chem. 2006, 14,4657–4663. Synthesis, anti-inflammatory and analgesic activity evaluation of Some amidine and hydrazone derivatives.
[31] Kwon-Chung, K.J., and Bennett, J.W. Med. Mycol. Lea. Febiger. Philadel. 1992, 81–102. Principles of antifungal and antibacterial therapy .
[2] Parmar, S.S., Pandey. B.R., Dwivedi, C., and Ali. B. J. Med. Chem. 1974, 17, 1031-1033. 3-Hydroxy-1-nitrophenyl-1(H-pyrazolo(3,4-b)pyridines as selective inhibitors of rat liver xanthine oxidase. [3] Zhmurenko, L.A., Molodavkin, G.M., Voronina, T.A., and Lezina, V.P. J.Pharm. Chem. 2012, 46, 15-19. Synthesis and antidepressant and anxiolytic activity of derivatives of pyrazolo[4,3-c]pyridine and 4-phenylhydrazinonicotinic acids .
[4] Dias, L.R.S., Alvim. M.J., Freitas. A.C., Barreiro. E.J., and Miranda, A.L.P. Pharm. Acta. Helv.1994, 69, 163-169. Synthesis and analgesic properties of 5-acyl-arylhydrazone 1-H pyrazolo [3,4-b] pyridine derivatives.
[5] Bare, T.M., McLaren, C.D., Campbell, J.B., Firor, J.W., Resch, J.F., Walters, C.P., Salama, A.I., Meiners, B.A., And Patel, J.B. J. Med. Chem. 1989, 32, 2561-2573.Synthesis and structure-activity relationships of a series of anxioselective pyrazolopyridine ester and amide anxiolytic agents. [6] Falco, J.L., Lloveras, M., Buira, I., Teixido, J., and Borrell, J.I. Eur. J. Med. Chem . 2005, 40, 1179-1187. Design, synthesis and biological activity of acyl substituted 3-amino-5-methyl-1,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones as potential hypnotic drugs.
[7] Bernardino, A.M.R., Azevedo, A.R., Pinheiro, L.C.S., Borges, J.C., Carvalho, V.L., Miranda, M.D., Meneses, M.D.F., Nascimento, M., Ferreira, D., Rebello, M.A., Silva, V.A.G., and Frugulhetti, I.C. Med. Chem. Res. 2007, 16, 352-369. Synthesis and Antiviral activity of new 4-(phenylamino)/4-[(methylpyridin-2-yl)amino]-1-phenyl-1H- pyrazolo[3,4-b]pyridine-4-carboxylic acids derivatives.
[8] Tucker, T.J., Sisko, J.T., Tynebor, R.M., Williams, T.M., Felock, P.J., Flynn, J.A., Lai, M.T., Liang, Y., McGaughey, G., Liu, M., Miller, M., Moyer, G., Munshi, V., Perlow-Poehnelt, R., Prasad, S., Reid, J.C., Sanchez, R., Torrent, M., Vacca, J.P., Wan, B.L., and Yan, Y. J. Med. Chem . 2008, 51, 6503-6511. Discovery of 3-{5-[(6-Amino-1H-pyrazolo[3,4-b]pyridine-3-yl)methoxy]-2-chlorophenoxy}-5-chlorobenzonitrile (MK-4965): A Potent, Orally Bioavailable HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor with Improved Potency against Key Mutant Viruses.
[9] Stasch, J.P., Dembowsky, K., Perzborn, E., Stahl, E., and Schramm, M.B. J. Pharmacol. 2002, 135, 344-355. Cardiovascular actions of a novel NO independent guanylyl cyclase stimulator, BAY 41-8543: in vivo studies.
[10] Dyck, B., Grigoriadis, D.E., Gross, R.S., Guo, Z., Marinkovic, D., McCarthy, J.R., Moorjani, M., Regan, C.F., Saunders, J., Schwaebe, M.K., Szabo, T., Williams, J.P., Zhang, X., Bozigian, H., and Chen, T.K. J. Med. Chem. 2005, 48,4100-4110. Potent, Orally Active Corticotropin-Releasing Factor Receptor-1 Antagonists Containing a Tricyclic Pyrrolopyridine or Pyrazolopyridine Core.
[11] Hoehn, H., Polacek, I., and Schulze, E. J. Med. Chem. 1973, 16, 1340-1346. Potential antidiabetic agents. Pyrazolo[3,4-b]pyridines.
[12] Kuczynski, L., Mrozikiewicz, A., Banaszkiewicz, W., and Poreba, K. Pol. J. Pharmacol.Pharm. 1979, 31, 217-225. Synthesis and biological activity of pyrazo-[3,4-b]-pyridine derivatives. Part I.
[13] Abdel-Aziz, H.A., Saleh, T.S., and El-Zahabi, H.A.S. Arch. Pharm. 2010, 343, 24-30. Facile Synthesis and In-Vitro Antitumor Activity of Some Pyrazolo[3,4-b]pyridines and Pyrazolo[1,5-a]pyrimidines Linked to a Thiazolo[3,2 a]benzimidazole Moiety.
[14] Cunico, W., Cechinel, C.A., Bonacorso, H.G., Martins, M.A., Zanatta, N., de Souza, M.V., Freitas, I.O., Soares, R.P., and Krettli, A.U. Bioorg. Med. Chem. Lett. 2006, 16, 649-653. Antimalarial activity of 4-(5-trifluoromethyl-1H pyrazol-1-yl)-chloroquine analogues
[15] El-Emary, T.I., Kamal El-Dean, A.M., and El-Kashef, H.S. II Farmaco, 1998, 53, 383-388. Facile synthesis of some new pyrazolo [3,4-b] pyrazines and their antifungal activity.
[16] El-Kashef, H.S., El-Emary, T.I., Gasquet, M., Timon-David, P., Maldonado, J., and Vanelle, P. Pharmazie, 2000, 55, 572-576. New pyrazolo[3,4-b]pyrazines: Synthesis and biological activity.
[17] El-Emary, T.I., and Abdel-Mohsen, S.A. Molecules, 2012, 17, 14464-14483. Multi-Component One-Pot Synthesis and Antimicrobial Activities of 3-Methyl- 1,4-diphenyl-7-thioxo-4,6,8,9-tetrahydropyrazolo[5,4-b]pyrimidino[5,4- e]pyridine-5-one and Related Derivatives.
[18] Bernardino, A.M.R., Rolim, A.M., and Castro, H.C. Bioorg. Med. Chem . 2006, 14, 5765–5770. Design, synthesis, SAR, and biological evaluation of new (phenylamino)pyrazolo[2,3-b]pyridine4- derivativesâ€.
[19] Wust, F., Kniess, T., Kretzschmar, M., and Bergmann, R. Bioorg. Med. Chem. Lett. 2005, 15,1303-1306. Synthesis and biodistribution of a 18F-labelled corticosteroid as ligand for mapping brain glucocorticoid receptors by means of PET.
[20] Helosia, D.M., Aurea, E., Alice, M.B., Marilene, C.C., and Leonor, L.L. J. Med. Chem. 2004, 47, 5427-5432. Antileishmanial Pyrazolopyridine Derivatives:Synthesis and Structure−Activity Relationship Analysis.
[21] Yu, G., Mason, H.J., Wu, X., Wang, J., Chong, S., Dorough, G., Henwood, A., Pongrac, R., Seliger, L., He, B., Normandin, D., Adam, L., Krupinski, J., and Macor, J.E. J. Med. Chem. 2001, 44, 1025-1027. Substituted pyrazolopyridines as potent and selective PDE5 inhibitors: potential agents for treatment of erectile dysfunction.
[22] El-Kashef, H.S. and El-Emary, T.I. J. Chem. Res. Synop. 1998, 20-21. Polycyclic Pyrazoles: Routes to New Pyrazoloazines.
[23] El-Emary, T.I., and Bakhite, E.A. Pharmazie, 1999, 54, 106-111. Synthesis and biological screening of new 1,3-diphenylpyrazoles with different heterocyclic moieties at position-4.
[24] El-Emary, T.I., Al-Muaikel, N., and Moustafa, O.S. Phosphorus Sulfur Silicon Relat. Elem.2002, 177, 195-210. Synthesis and Antimicrobial Activity of some New Heterocycles Based on 3-Methyl-1-Phenyl-5-Benzene Sulfonamido Pyrazole.
[25] El-Emary, T.I., Khalil, A., El-Hag, G.A., and El-Adasy, M. A. Phosphorus Sulfur Silicon Relat. Elem. 2005, 180, 19-30. A Facile Synthesis of Some New Thiazolo[3, 2]pyridines Containing Pyrazolyl Moiety and Their Antimicrobial Activity.
[26] Haeufel ,J., and Breitmeir, E. Angew. Chem. Int. Ed. Engl. 1974, 13: 604-609. Synthesis of Pyrazolo Heteroaromatic Compounds by Means of 5-Amino-3-methyl-1-phenylpyrazole-4-carbaldehyde.
[27] El-Emary, T.I. j. Chin. Chem. Soc.2007, 54, 507-518. Synthesis of Newly Substituted Pyrazoles and Substituted Pyrazolo[3,4-b]pyridines Based on 5-Amino-3-methyl-1-phenylpyrazole.
[28] Haythem, A.S., Ibrahim, M. M., Amal, G.A., and Mohammad, S.M. Monatsh. Chem. 2010, 141,471–478.Synthesis and antimicrobial activity of new 1,2,4-triazole-3-thiol metronidazole derivatives.
[29] Saravanan, S., Nithya, A., and Muthusubramanian, S. J. heterocycl. Chem. 2006, 43, 149-155. Synthesis and characterization of 4-aryl-5-(1-aryl-2-methyl-2-nitropropyl)-1,2,3-selenadiazoles .
[30] Sondhi, S.M., Dinodia, M., and Kumar, .A. Bioorg. Med. Chem. 2006, 14,4657–4663. Synthesis, anti-inflammatory and analgesic activity evaluation of Some amidine and hydrazone derivatives.
[31] Kwon-Chung, K.J., and Bennett, J.W. Med. Mycol. Lea. Febiger. Philadel. 1992, 81–102. Principles of antifungal and antibacterial therapy .
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2014-01-22
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Abdelmohsen, S. A., & Emary, T. I. E. (2014). SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL ACTIVITY OF NOVEL PYRAZOLO[3,4-b]PYRIDINES AND THEIR SPIRO-HETEROCYCLIC DERIVATIVES. JOURNAL OF ADVANCES IN CHEMISTRY, 10(7), 2901–2915. https://doi.org/10.24297/jac.v10i7.6802
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