DOI: https://doi.org/10.15587/2519-4852.2017.113493

Products of interaction of substituted 5-aminopyrazoles with α -haloketones as potential pharmaceutical agents

Pavlo Tkachenko, Olena Tkachenko, Krystyna Netosova, Oleksandr Borisov, Iryna Zhuravel

Abstract


Aim. Optimization of reaction of substituted 5-aminopyrazoles with a-haloketones to form annealed 2,6,7-trisubstituted 1H-imidazo[1,2-b]pyrazoles.

Materials and methods of research. The methods of organic synthesis, instrumental methods of organic compound analysis were used.

Results. A scheme for the synthesis of 2,6,7-trisubstituted 1H-imidazo[1,2-b]pyrazoles by the interaction of 5-amino-4-arylsulfonyl-3-methylthiopyrazoles 1a-b with chloroacetone, phenacyl bromide and 2-chlorocyclohexanone was developed. In contrast to the previously described interaction of substituted 5-aminopyrazoles with chloro (N-aryl) acetamides proceeding exclusively with the release of N1-alkylation products, in this reaction a mixture of N1- and N2-isomeric alkylation products is formed. The ratio of isomers depends on the nature of the reagents and, according to the 1H NMR-spectroscopy, is about 60:40 %.The developed technique allows with one of the synthetic procedure to carry out N1-alkylation of 5-aminopyrazoles 1a-b and the cyclization of products 2 in imidazo[1,2-b]pyrazoles 4a-c without isolating the N2-alkylation product. The purity of the obtained compounds is proved chromatographically, the structure is confirmed by the data of 1H NMR-spectroscopy.

Conclusions. Optimized reaction of substituted 5-aminopyrazoles with a-haloketones to form annealed 2,6,7-trisubstituted 1H-imidazo[1,2-b]pyrazoles for targeted synthesis of the novel agents for the pharmaceutical practice


Keywords


pyrazole; -haloketones; 1H-imidazo[1;2-b]pyrazoles; synthesis; alkylation; pharmaceutical agents; NMR spectroscopy; isomerism

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References


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Tkachenko, P. V., Tkachenko, O. V., Netosova, K. Y., Borisov, O. V., Zhuravel, I. O. (2017). The synthesis of the substituted 4-alkyl/arylsulfonyl-5-amino-3-alkylthiopyrazoles as promising pharmaceutical agents with the antifungal action. Visnik Farmacii, 2 (90), 25–30. doi: 10.24959/nphj.17.2158


GOST Style Citations


Ansari, A. Review: biologically active pyrazole derivatives [Text] / A. Ansari, A. Ali, M. Asif, S. Shamsuzzaman // New Journal of Chemistry. – 2017. – Vol. 41, Issue 1. – P. 16–41. doi: 10.1039/c6nj03181a

Li, Y.-R. Synthesis and biological evaluation of 1,3-diaryl pyrazole derivatives as potential antibacterial and anti-inflammatory agents [Text] / Y.-R. Li, C. Li, J.-C. Liu, M. Guo, T.-Y. Zhang, L.-P. Sun et. al. // Bioorganic & Medicinal Chemistry Letters. – 2015. – Vol. 25, Issue 22. – P. 5052–5057. doi: 10.1016/j.bmcl.2015.10.028

Basha, S. S. Synthesis and antimicrobial activity of 3-aroyl-4-heteroaryl pyrroles and pyrazoles [Text] / S. S. Basha, P. Ramachandra Reddy, A. Padmaja, V. Padmavathi, K. C. Mouli, T. Vijaya // Medicinal Chemistry Research. – 2015. – Vol. 24, Issue 3. – P. 954–964. doi: 10.1007/s00044-014-1169-8

Weston, C. E. Toward Photopharmacological Antimicrobial Chemotherapy Using Photoswitchable Amidohydrolase Inhibitors [Text] / C. E. Weston, A. Kramer, F. Colin, O. Yildiz, M. G. J. Baud, F.-J. Meyer-Almes, M. J. Fuchter // ACS Infectious Diseases. – 2017. – Vol. 3, Issue 2. – P. 152–161. doi: 10.1021/acsinfecdis.6b00148

Patil, A. Synthesis and antifungal activities of diaryl pyrazoles carboxamide derivatives [Text] / A. Patil, R. Jadhav, H. Raundal, L. Sharma, R. Badgujar, V. Bobade // Journal of Chemical and Pharmaceutical Research. – 2014. – Vol. 6, Issue 8. – P. 218–223.

Lei, P. Synthesis and fungicidal activity of pyrazole derivatives containing 1,2,3,4-tetrahydroquinoline [Text] / P. Lei, X. Zhang, Y. Xu, G. Xu, X. Liu, X. Yang et. al. // Chemistry Central Journal. – 2016. – Vol. 10, Issue 1. doi: 10.1186/s13065-016-0186-8

Bekhit, A. A. Synthesis and biological evaluation of some thiazolyl and thiadiazolyl derivatives of 1H-pyrazole as anti-inflammatory antimicrobial agents [Text] / A. A. Bekhit, H. M. A. Ashour, Y. S. Abdel Ghany, A. E.-D. A. Bekhit, A. Baraka // European Journal of Medicinal Chemistry. – 2008. – Vol. 43, Issue 3. – P. 456–463. doi: 10.1016/j.ejmech.2007.03.030

Ai, T. N-(1-Benzyl-3,5-dimethyl-1H-pyrazol-4-yl)benzamides: Antiproliferative Activity and Effects on mTORC1 and Autophagy [Text] / T. Ai, R. Willett, J. Williams, R. Ding, D. J. Wilson, J. Xie et. al. // ACS Medicinal Chemistry Letters. – 2017. – Vol. 8, Issue 1. – P. 90–95. doi: 10.1021/acsmedchemlett.6b00392

Kaufmann, K. ML297 (VU0456810), the First Potent and Selective Activator of the GIRK Potassium Channel, Displays Antiepileptic Properties in Mice [Text] / K. Kaufmann, I. Romaine, E. Days, C. Pascual, A. Malik, L. Yang et. al. // ACS Chemical Neuroscience. – 2013. – Vol. 4, Issue 9. – P. 1278–1286. doi: 10.1021/cn400062a

Krogsgaard-Larsen, P. Textbook of Drug Design and Discovery [Text] / P. Krogsgaard-Larsen, K. Stromgaard, U. Madsen. – Florida: CRC Press, 2010. – 460 p.

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Tkachenko, P. V. The synthesis and the antimicrobial activity of N1-substituted 5-amino-4-arylsulfonyl-3-N-phenylaminopyrazoles [Text] / P. V. Tkachenko, O. V. Tkachenko, K. Y. Netosova, O. V. Borisov, I. O. Zhuravel, V. V. Kazmirchuk // Visnik Farmacii. – 2017. – Issue 3 (91). – P. 3–9. doi: 10.24959/nphj.17.2159

Tkachenko, P. V. The synthesis of the substituted 4-alkyl/arylsulfonyl-5-amino-3-alkylthiopyrazoles as promising pharmaceutical agents with the antifungal action [Text] / P. V. Tkachenko, O. V. Tkachenko, K. Y. Netosova, O. V. Borisov, I. O. Zhuravel // Visnik Farmacii. – 2017. – Vol. 2, Issue 90. – P. 25–30. doi: 10.24959/nphj.17.2158







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