Synthesis of novel pyrazolo[3,4-d]pyrimidinone derivatives as cytotoxic inhibitors

Authors

  • Ameur Rahmouni Laboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivité, Equipe: Chimie Médicinale et Produits Naturels, Faculté des Sciences de Monastir, Université de Monastir, Avenue de l’Environnement, 5019 Monastir, Tunisie
  • Anis Romdhane Laboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivité, Equipe: Chimie Médicinale et Produits Naturels, Faculté des Sciences de Monastir, Université de Monastir, Avenue de l’Environnement, 5019 Monastir, Tunisie
  • Malek Besbes Laboratoire des maladies transmissibles et des substances biologiquement actives, Faculté de Pharmacie, 5000 Monastir, Tunisie
  • Nicolas Elie Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France
  • David Touboul Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France
  • Hichem Ben Jannet Laboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivité, Equipe: Chimie Médicinale et Produits Naturels, Faculté des Sciences de Monastir, Université de Monastir, Avenue de l’Environnement, 5019 Monastir, Tunisie

DOI:

https://doi.org/10.13171/mjc.2.4.2014.11.02.23

Abstract

Various α-fonctionalized iminoethers 2 were easily prepared from ethyl 5-amino-3-substituted-1-phenyl-1H-pyrazole-4-carboxylate 1. The reaction of iminoethers 2 with ammonia afforded 3-substitued-1-phenyl-1H-pyrazolo[3,4-d] pyrimidin-4(5H)-ones 3 which were also synthesized by the addition of formamide to ethyl 5-amino-3-substituted-1-phenyl-1H-pyrazole-4-carboxylate 1. The 5-amino-3-substitued-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones 4 were obtained from hydrazonolysis of iminoethers 2. Otherwise, the condensation of these intermediates 2 with a series of some primary amines and hydroxylamine led respectively, to the corresponding 3,5-disubstitued-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones 5 and the 3-substitued-5-hydroxy-1-phenyl-1H-pyrazolo[3,4-d] pyrimidin-4-(5H)-ones 6. The synthesized compounds 1-6 were completely characterized by 1H NMR, 13C NMR, IR and HRMS. Some synthesized compounds were evaluated for their cytotoxic effect using the Human cervical adenocarcinoma Hela cell line.

References

- J. K. Gupta, C. Anshu, D. Rupesh, V. Kumari, P. K. Sharma, P. K. Verma, International Journal of Pharmaceutical Sciences and Research, 2010, 5, 0975-8232.

- M. H. Elnagdi, E. M. Kandeel, E. M. Zayed, Z. E. Kandeel, J. Heterocycl. Chem., 1977, 14, 155-157.

- A. E. Rashad, M. I. Hegab, R. E. Abdel-Megeid, N. Fathalla, F. M. E. Abdel-Megeid, Eur. J. Med. Chem., 2009, 44, 3285-3292.

- N. C. Desai , V.V. Joshi, K. M. Rajpara, H. V. Vaghani, H. M. Satodiya, Journal of Fluorine Chemistry, 2012, 142, 67-78.

- R. A. Mekheimer, E. A. Ahmed, K. U. Sadek, Tetrahedron, 2012, 68, 1637-1667.

- H. A. Stefani, C. M. P. Pereira, R. B. Almeida, R. C. Braga, K. P. Guzen, R. Cella, Tetrahedron Lett.,2005, 46, 6833-6837.

- A. M. Youssef, E. G. Neeland, E. B. Villanueva, M. S. White, I. M. El-Ashmawy, B. Patrick, A. Klegeris, A. S. Abd-El-Aziz, Bioorg. Med. Chem, 2010, 18, 5685-5696.

- J. P. Colomer, E.L. Moyano, Tetrahedron Lett.,2011, 52, 1561-1565.

- B. S. Holla, M. Mahalinga, M. S. Karthikeyan,P. M. Akberalib, N. S. Shetty, Bioorg. Med. Chem., 2006, 14, 2040-2047.

- M. M. El-Enany, M. M. Kamel, O. M. Khalil, H. B. El-Nassan, Eur. J. Med. Chem., 2010, 45, 5286-5291.

- D. C. Kim, Y. R. Lee, B. S. Yang, K. J. Shin, D. J. Kim, B. Y. Chung, K. H. Yoo, Eur. J. Med. Chem., 2003, 38, 525-532.

- S. Schenone, C. Brullo, O. Bruno,F. Bondavalli, L. Mosti, G. Maga,E. Crespan, F. Carraro, F. Manetti, C. Tintori, M. Botta, Eur .J. Med. Chem., 2008, 43, 2665-2676.

- M. M. Ghorab, F. A. Ragab, S. I. Alqasoumi, A. M. Alafeefy, S. A. Aboulmagd, Eur. Med. Chem., 2010, 45, 171-178.

- M. Ge, E. Cline, L. Yang, Tetrahedron Lett.,2006, 47, 5797-5799.

- K. M. Al-Taisan, H. M. Al-Hazimi, S. Al-Shihry, Molecules, 2010,15, 3932-3957.

- E. I. Al-Afleq, S. A. Abubshait, Molecules, 2001, 6, 621-638.

- P. G. Baraldi, H. El-Kashef, A. Farghaly, P. Vanelle, F. Fruttarolo, Tetrahedron, 2004, 60,5093-5098.

- A. M. F. Oliveira-Campos, A. M. Salaheldin, L. M. Rodrigues, ARKIVOC, 2007, (xvi), 92-100.

- S. Gupta, L. M. Rodrigues, A. P. Esteves, A. M. F. Oliveira-Campos, M. S. J. Nascimento, N. Nazareth, H. Cidade, M. P. Neves, E. Fernandes, M. Pinto, N. M. F. S. A. Cerqueira, N. Bras, Eur. J. Med. Chem., 2008, 43, 771-780.

- M. S. Nermien, M. M. Hany, E. S. A. E. H. Khattab, S. S. Motlaq, A. M. El-Agrody, Eur. J. Med. Chem., 2011, 46, 765-772.

- R. Yan, Y. Yang, Y. Zeng, G. Zou, J. Ethnopharmacol., 2009, 121, 451-455.

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Published

2014-02-11

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Section

Inorganic Chemistry