METHODS FOR SYNTHESIZING FUNCTIONALIZED CYCLIC ENAMINITRILES
DOI:
https://doi.org/10.15407/dopovidi2025.05.003Keywords:
pyrrolidinylidene, hetarylacetonitriles, heterocycles, imidoyl chlorides, heterocyclization recyclization, cyclizationAbstract
A number of effective approaches to the synthesis of 2-hetaryl-2-(1-aryl(hetaryl)pyrrolidin-2-ylidene)acetonitriles have been developed. The methods are based on various ways of constructing the pyrrolidinylidene ring. These include the recycling of 2-hetaryl-2-(tetrahydro-2-furanilidene)acetonitriles upon interaction with aromatic amines, as well as the condensation of alicyclic and cyclic imidoyl chlorides with hetarylacetonitriles. The ap- proaches studied allow for variation in both the structure of the hetarylacetonitrile fragment and the structure of the N-substituents of the pyrrolidin ring, including electron-rich and heteroaromatic ones. The structure of the obtained compounds has been established and confirmed by NMR spectroscopy. Pyrrolidine-containing com- pounds have a wide spectrum of pharmacological activity, therefore the obtained products can be considered promising compounds for biological screening.
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Bhat, A. A., Singh, I., Tandon, N. & Tandon, R. (2023). Structure activity relationship (SAR) and anticancer activity of pyrrolidine derivatives: Recent developments and future prospects (A review). Eur. J. Med. Chem. 246, 114954. https://doi.org/10.1016/j.ejmech.2022.114954
Finiuk, N., Kryshchyshyn-Dylevych, A., Holota, S., Klyuchivska, O., Kozytskiy, A., Karpenko, O., Manko, N., Ivasechko, I., Stoika, R. & Lesyk, R. (2022). Novel hybrid pyrrolidinedione-thiazolidinones as potential anticancer agents: Synthesis and biological evaluation. Eur. J. Med. Chem., 238, 114422. https://doi.org/10.1016/j. ejmech.2022.114422
Hassan, A. H. E., Park, H. R., Yoon, Y. M., Kim, H. I., Yoo, S. Y., Lee, K. W. & Lee, Y. S. (2019). Antiproliferative 3-deoxysphingomyelin analogs: Design, synthesis, biological evaluation and molecular docking of pyrrolidine- based 3-deoxysphingomyelin analogs as anticancer agents. Bioorg. Chem., 84, pp. 444-455. https://doi. org/10.1016/j.bioorg.2018.11.040
Fatahala, S. S., Hasabelnaby, S., Goudah, A., Mahmoud, G. I. & Abd-El Hameed, R. H. (2017). Pyrrole and fused pyrrole compounds with bioactivity against inflammatory mediators. Molecules, 22, No. 3, 461. https://doi. org/10.3390/molecules22030461
Yao, C.-P., Zou, Z.-X., Zhang, Y., Li, J., Cheng, F., Xu, P.-S., Zhou, G., Li, X.-M., Xu, K.-P. & Tan, G.-S. (2019).
New adenine analogues and a pyrrole alkaloid from Selaginella delicatula. Nat. Prod. Res., 33, No. 14, pp. 1985- 1991. https://doi.org/10.1080/14786419.2018.1482892
Liu, P., Yang, Y., Ju, Y., Tang, Y., Sang, Z., Chen, L., Yang, T., An, Q., Zhang, T. & Luo, Y. (2018). Design, synthesis and biological evaluation of novel pyrrole derivatives as potential ClpP1P2 inhibitor against Mycobacterium tuberculosis. Bioorg. Chem., 80, pp. 422-432. https://doi.org/10.1016/j.bioorg.2018.06.004
Aboul-Enein, M. N., El-Azzouny, A. A. E.-S., Saleh, O., Maklad, Y. A., Aboutabl, M. E. & El-Din, M. M. G. (2016). Synthesis, bio-evaluation and molecular modeling studies of (2S)-1-[({[1-substituted cyclohexyl] methyl}amino)acetyl]pyrrolidine-2-carbonitriles for their DPP-4 inhibiting activity. Int. J. Pharm. Sci. Rev. Res., 39, No. 2, pp. 230-240.
Shemehen, R., Khilya, О. & Volovenko, Yu. (2020). Reaction of 2-hetaryl-2-(dihydrofuran-2(3H)-iliden) acetonitriles with aromatic amines. Bulletin of Taras Shevchenko National University of Kyiv, Chemistry, No. 1 (57), pp. 42-46 (in Ukrainian). https://doi.org/10.17721/1728-2209.2020.1(57).12
Eilingsfeld, H., Seefelder, M. & Weidinger, H. (1960). Amidchloride und carbamidchloride. Angew. Chem., 72, No. 22, pp. 836-845. https://doi.org/10.1002/ange.19600722
Zhaowen, L., Li, Z., Chunfen, X., Yong, Y., Fanbo, Z. & Kaixun, H. (2007). Anticancer activities of some arylca rbamoylalkyltriphenylphosphonium chlorides. Med. Chem. Res., 16, No. 7-9, pp. 380-391. https://doi. org/10.1007/s00044-007-9050-7
El-Ahmad, Y., Maillet, P., Laurent, E., Talab, A., Tran, G. & Ollivier, R. (1997). Synthesis of 1-[ω-[(arylamino) carbonyl]-alkyl]-4-(benzocycloalkyl)piperazines. HETEROCYCLES, 45, No. 4, pp. 723-734. https://doi. org/10.3987/com-97-7736
Lebedev, A. T., Mazur, D. M., Kudelin, A. I., Fedotov, A. N., Gloriozov, I. P., Ustynyuk, Yu. A. & Artaev, V. B. (2016). Cyclization of N-arylcyclopropanecarboxamides into N-arylpyrrolidin-2-ones under electron ionization and in the condensed phase. Rapid Commun. Mass Spectrom., 30, No. 22, pp. 2416-2422. https://doi. org/10.1002/rcm.7717
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