Synthesis and potential biological activity of some novel 3-[(N-substituted indol-3-yl)methyleneamino]-6-amino-4-aryl-pyrano(2,3-c)pyrazole-5-carbonitriles and 3,6-diamino-4-(N-substituted indol-3-yl)pyrano(2,3-c)pyrazole-5-carbonitriles

Open access

Synthesis and potential biological activity of some novel 3-[(N-substituted indol-3-yl)methyleneamino]-6-amino-4-aryl-pyrano(2,3-c)pyrazole-5-carbonitriles and 3,6-diamino-4-(N-substituted indol-3-yl)pyrano(2,3-c)pyrazole-5-carbonitriles

Starting from N-substituted indole-3-carboxaldehydes (1a-g) a series of new 3-[(N-substituted indol-3-yl)methyleneamino]-6-amino-4-aryl-pyrano(2,3-c)pyrazole-5-carbonitriles (3a-g and 4a-g) have been synthesized via the acid catalyzed condensation reaction of 1a-g with 3-amino-5-pyrazolone, followed by the reaction with arylidene malononitriles. A series of new 3,6-diamino-4-(N-substituted indol-3-yl)pyrano(2,3-c)pyrazole-5-carbonitriles (7a-g) have been prepared either via the base catalyzed condensation reaction of 1a-g with 3-amino-5-pyrazolone to give 6a-g, followed by the reaction with malononitrile or by the reaction of N-substituted-3-indolylidene malononitriles (5a-g) with 3-amino-5-pyrazolone. According to the obtained results, the newly synthesized compounds possess significant anti-inflammatory, analgesic and anticonvulsant activities. The anticonvulsant potency of certain tested compounds was more pronounced than both anti-inflammatory and analgesic activities. Moreover, most of the newly synthesized compounds possess potential antimicrobial activity against Escherichia coli and Pseudomonas aeruginosa.

Sinteza i potencijalno biološko djelovanje novih 3-((N-supstituiranih indol-3-il)metilenamino)-6-amino-4-aril-pirano(2,3-c)pirazol-5-karbonitrila i 3,6-diamino-4-(N-supstituiranih indol-3-il)pirano(2,3-c)pirazol-5-karbonitrila

U radu se opisuje sinteza novih 3-[N-supstituiranih indol-3-il)metilenamino]6-amino-4-aril-pirano(2,3-c) pirazol-5-karbonitrila (3a-g i 4a-g) kiselo-kataliziranom kondenzacijom N-supstituiranih indol-3-karboksaldehida (1a-g) s 3-amino-5-pirazolonom iza koje slijedi reakcija s ariliden malononitrilom. Serija novih 3,6-diamino-4-(N-supstituiranih indol-3-il)pirano(2,3-c)pirazol-5-karbonitrila (7a-g) sintetizirana je reakcijom malononitrila s produktima 6a-g, koji su pripravljeni bazno-kataliziranom kondenzacijom 1a-g s 3-amino-5-pirazolonom. Neki spojevi iz serije 7a-g dobiveni su reakcijom N-supstituiranih 3-indolidin malononitrila (5a-g) s 3-amino-5-pirazolonom. Novosintetizirani spojevi imaju značajno protuupalno, analgetsko i antikonvulzivno djelovanje. Antikonvulzivno djelovanje pojedinih testiranih spojeva bilo je jače izraženo nego protuupalno i analgetsko djelovanje. Većina ispitivanih spojeva pokazuje antimikrobno djelovanje na Escherichia coli i Pseudomonas aeruginosa.

  • P. Rani, V. K. Srivastava and A. Kumar, Synthesis and anti-inflammatory activity of heterocyclic indole derivatives, Eur. J. Med. Chem. 39 (2004) 449-452; DOI: 10.1016j.egmech2003.11.002.

  • M. Amir, S. A. Javed and H. Kumar, Synthesis and biological evaluation of some 4-(1H-indol-3-yl)-6-phenyl-1,2,3,4-tetrahydropyrimidin-2-ones/thiones as potent anti-inflammatory agents, Acta Pharm. 58 (2008) 467-477; DOI: 10.2478/v10007-008-0028-x.

  • A. H. Mandour, E. R. El-Sawy, K. H. Shaker and M. A. Mustafa, Synthesis, anti-inflammatory, analgesic and anticonvulsant activities of 1,8-dihydro-1-aryl-8-alkyl pyrazolo(3,4-b)indole, Acta Pharm. 60 (2010) 73-88; DOI: 10.2478/v10007-010-0009-8.

  • N. Siddiqui, M. S. Alam and W. Ahsan, Synthesis, anticonvulsant and toxicity evaluation of 2-(1H-indol-3-yl)acetyl-N-(substituted phenyl) hydrazine carbothioamides and their related heterocyclic derivatives, Acta Pharm. 58 (2008) 445-454; DOI:10.2478/v10007-008-0025-0.

  • M. A. A. Radwan, E. A. Ragab, N. M. Sabrya and S. M. El-Shenawy, Synthesis and biological evaluation of new 3-substituted indole derivatives as potential anti-inflammatory and analgesic agents, Bioorg. Med. Chem. 15 (2007) 3832-3841; DOI: 10.1016/j.bmc.2007.03.024.

  • E. R. El-Sawy, F. A. Bassyouni, S. H. Abu-Bakr, H. M. Rady and M. M. Abdlla, Synthesis and biological activity of some new 1-benzyl and 1-benzoyl 3-heterocyclic indole derivatives, Acta Pharm. 60 (2010) 55-71; DOI: 10.2478/v10007-010-0004-0.

  • S. George, M. P. Waran, A. Chakraborty and T. K. Ravi, Synthesis and evaluation of the biological activities of some 3-[5-(6-methyl-4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidin-5-yl)-1,3,4-oxadiazol-2-yl]-imino-1,3-di-hydro-2H-indol-2-one derivatives, Acta Pharm. 58 (2008) 119-129; DOI: 10.2478/v10007-007-0050-4.

  • M. E. Zaki, H. A. Soliman, O. A. Hiekal and A. E. Z. Rashad, Pyrazolopyranopyrimidines as a class of anti-inflammatory agents, Z. Naturforsch. C 61 (2006) 1-5.

  • S. G. Kuo, L. J. Huang and H. Nakamura, Studies on heterocyclic compounds. 6. Synthesis and analgesic and anti-inflammatory activities of 3,4-dimethylpyrano[2,3-c]pyrazol-6-one derivatives, J. Med. Chem. 27 (1984) 539-544.

  • R. M. Abd El-Aal and M. Younis, Synthesis and antimicrobial activity of certain novel monomethine cyanine dyes, Dyes Pigments 60 (2004) 205-214; DOI: 10.1016/S0143-7208(03)00131-1.

  • H. M. Al-Matar, K. D. Khalil, A. Y. Adam and M. H. Elnagdi, Green one pot solvent-free synthesis of pyrano[2,3-c]-pyrazoles and pyrazolo[1,5-a]pyrimidines, Molecules 15 (2010) 6619-6629; DOI: 10.3390/molecules15096619.

  • A. M. Shestopalov, A. P. Yakubov, D. V. Tsyganov, E. Yanova, M. Yu and V. N. Nesterov, One-pot synthesis of diverse 4-di(tri)fluoromethyl-3-cyanopyridine-2(1H)-thiones and their utilities in the cascade synthesis of annulated heterocycles, Chem. Heterocyc. Compd. 38 (2002) 1180-1189; DOI: 10.1021/cc7001793.

  • S. Gogoi and C. Zhao, Organocatalyzed enantioselective synthesis of 6-amino-5-cyanodihydropyrano[2,3-c]pyrazole, Tetrahedron Lett. 50 (2009) 2252-2255; DOI: 10.1016/j.tetlet.2009.02.210.

  • A. L. Mndzhoyan, G. L. Papayan, L. D. Zhuruli, S. G. Karagezyan, L. S. Galstyan and V. G. Sarafyan, Synthesis and biological study of hydrazinohydrazones of indole aldehydes and ketons series, Arm. Khim. Zh. (USSR) 22 (1969) 707-713; ref. Chem. Abstr. 72 (1970) 11189f.

  • A. H. Mandour, E. R. El-Sawy, M. A. Zahran, M. S. Ebaid and M. A. Mustafa, Anti-inflammatory, analgesic, anticonvulsant and antimicrobial activities of some new synthesized N-alkyl-3-indolyl pyrimidines and benzimidazolo(1,2-a) pyrimidines, Biohealth Sci. Bull. (Malaysia) 1 (2009) 57-67.

  • M. G. Obukowicz, D. J. Welsch, W. J. Salsgiver, M. Berger, K. S. Chinn and K. L. Duffin, Novel, selective delta6 or delta5 fatty acid desaturase inhibitors as anti-inflammatory agents in mice, J. Pharmacol. Exp. Ther. 287 (1998) 157-162.

  • C. A. Winter, E. A. Risely and G. W. Nuss, Anti-infalmmatory and antipyretic activities of indomethacin, 1-(p-chlorobenzyl)-5-methoxy-2-methyl-indole-3-acetic acid, J. Pharmacol. Exp. Ther. 141 (1963) 369-376.

  • R. Okun, S. C. Liddon and L. Lasagna, Effect of reserpine pre-treatment on the protective action of amphetamine and phenoxy propazine in the phenylbenzoquinone-induced writhing syndrome in mice, J. Pharm. Exp. Ther. 139 (1963) 107-110; DOI: 10.1038/201306a0.

  • Drug Discovery and Evaluation: Pharmacological Assays, Chapter E: Psychotropic and Neurotropic Activity (Eds. H. G. Vogel and W. H. Vogel, Springer-Verlag), Berlin 1997, pp. 260-261.

  • A. L. Barry and C. Thornsberry, Susceptibility Testing: Diffusion Test Procedures, in Manual of Clinical Microbiology (Eds. E. H. Lennette, A. Balows, W. J. Hausler, Jr. and J. P. Truant), 3rd ed., American Society for Microbiology, Washington (DC) 1980, pp. 463-474.

Acta Pharmaceutica

The Journal of Croatian Pharmaceutical Society

Journal Information

IMPACT FACTOR 2016: 1.288
5-year IMPACT FACTOR: 1.600

CiteScore 2016: 1.55

SCImago Journal Rank (SJR) 2016: 0.353
Source Normalized Impact per Paper (SNIP) 2016: 0.854


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 31 31 19
PDF Downloads 4 4 3