In this study, a new tandem method was developed for the synthesis of thiazole-substituted pyrrolo[1,2-d][1,2,4]triazin-4(3H)-one derivatives. The method consists of a tandem reaction involving a subsequent formation of first the thiazole and then the triazine ring upon the addition of phenacyl bromide to a product of the condensation reaction between ethyl 2-formyl-1H-pyrrole- 1-carboxylate and thiosemicarbazide. The tandem cyclization step was completed in just 30 minutes. In order to predict the reaction mechanism, the charge densities of atoms and HOMO and LUMO energy were calculated by DFT method for the compounds obtained in the intermediate stage. In addition, a series of pyrrolotriazinone derivatives synthesized in high yields by this method were found to be suitable drug candidates according to their druglikeness and theoretical pharmacokinetic profiles.
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Beck, H.; Härter, M.; Haß, B.; Schmeck, C.; Baerfacker, L. Drug Discovery Today 2022, 27, 1560.
Maurer, T. S.; Edwards, M.; Hepworth, D.; Verhoest, P.; Allerton, C. M. Drug Discovery Today 2021, 27, 538.
Reymond, J.-L.; Van Deursen, R.; Blum, L. C.; Ruddigkeit, L. Med. Chem. Comm. 2010, 1, 30.
Raker, J. R.; Towns, M. H. Chem. Educ. Res. Pract. 2012, 13(3), 179.
Li, Q. Front. Mol. Biosci. 2020, 7, 180.
Zhang, K. Y.; Milburn, M. V.; Artis, D. R. Structure-Based Drug Discovery; Jhoti, H.; Leach, A. R., Eds.; Springer: Dordrecht, 2007, p. 129.
Vitaku, E.; Smith, D. T.; Njardarson, J. T. J. Med. Chem. 2014, 57, 10257.
Kerru, N.; Gummidi, L.; Maddila, S.; Gangu, K. K.; Jonnalagadda, S. B. Molecules 2020, 25, 1909.
Ge, T.; Cintrat, J. C. Pharmaceuticals 2021, 14, 1275.
Saito, T.; Obitsu, T.; Kohno, H.; Sugimoto, I.; Matsushita, T.; Nishiyama, T.; Hirota, T.; Takeda, H.; Matsumura, N.; Ueno, S.; Kishi, A.; Kagamiishi, Y.; Nakai, H.; Takaoka, Y. Bioorg. Med. Chem. 2012, 20, 1122.
Devasthale, P.; Wang, W.; Mignone, J.; Renduchintala, K.; Radhakrishnan, S.; Dhanapal, J.; Selvaraj, J.; Kuppusamy, R.; Pelleymounter, M. A.; Longhi, D.; Huang, N.; Flynn, N.; Azzara, A. V.; Rohrbach, K.; Devenny, J.; Rooney, S.; Thomas, M.; Glick, S.; Godonis, H.; Harvey, S.; Cullen, M. J.; Zhang, H.; Caporuscio, C.; Stetsko, P.; Grubb, M.; Huang, C.; Zhang, L.; Freeden, C.; Murphy, B. J.; Robl, J. A.; Washburn, W. N. Bioorg. Med. Chem. Lett. 2015, 25, 4412.
Jia, H.; Dai, G.; Su, W.; Xiao, K.; Weng, J.; Zhang, Z.; Bembenek, S. D. J. Med. Chem. 2019, 62, 4936.
Naef, R.; Tenor, H. WO Patent WO2017085056.
Li, J.; Wang, L.; Yang, M. CN Patent CN105669680.
Wu, Y.; Wang, L.; Yang, X.; Tian, Y. CN Patent CN108341819.
Zhao, C.; Zhang, R.; He, B.; Wei, N.; Wu, Y.; Zhou, T. CN Patent CN103848835.
Jebamani, J.; Pranesh, S.; Shivalingappa, J.; Narayanarao, M.; Pasha, M. Synth. Commun. 2021, 51, 921.
Montoir, D.; Guillon, R.; Gazzola, S.; Ourliac-Garnier, I.; Soklou, K. E.; Tonnerre, A.; Picot, C.; Planchat, A.; Pagniez, F.; Le Pape, P.; Logé, C. Eur. J. Med. Chem. 2020, 189, 112082.
Loge, C.; Guillon, R.; Montoir, D. Pagniez, F.; Le Pape, P. EP Patent WO2017020944.
Kuzu, B.; Gül, S.; Tan, M.; Menges, N.; Balci, M. ChemistrySelect 2021, 6, 2366.
Hasan, I.; Marinelli, E. R.; Lin, L.-C. C.; Fowler, F. W.; Levy, A. B. J. Org. Chem. 1981, 46, 157.
Turan, G.; Osmaniye, D.; Sağlik, B. N.; Cevik, U. A.; Levent, S.; Çavuşoğlu, B. K.; Ozkay, U. D.; Ozkay, Y.; Kaplancikli, Z. A. Phosphorus, Sulfur Silicon Relat. Elem. 2020, 195, 491.
Lipinski, C. A. Annu. Rep. Comput. Chem. 2005, 1, 155.
Mignani, S.; Rodrigues, J.; Tomas, H.; Jalal, R.; Singh, P. P.; Majoral, J.-P.; Vishwakarma, R. A. Drug Discovery Today 2018, 23, 605.
Cumming, J. G.; Davis, A. M.; Muresan, S.; Haeberlein, M.; Chen, H. Nat. Rev. Drug Discovery 2013, 12, 948.
Cheng, F.; Li, W.; Liu, G.; Tang, Y. Curr. Top. Med. Chem. 2013, 13, 1273.
Guven, S.; Ozer, M. S.; Kaya, S.; Menges, N.; Balci, M. Org. Lett. 2015, 17, 2660.
Roques, B.; Jaureguiberry, C.; Fournie-Zaluski, M. C.; Combrisson, S. Tetrahedron Lett. 1971, 12, 2693.
Rainey, J. L.; Adkins, H. J. Am. Chem. Soc. 1939, 61, 1104.
Normaya, E.; Baharu, N. A.; Ahmad, M. N. J. Mol. Struct. 2020, 1212, 128094.
Gaffer, H. E.; Khalifa, M. E. Molecules 2015, 20, 21982.
Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Petersson, G. A.; Nakatsuji, H.; Li, X.; Caricato, M.; Marenich, A.; Bloino, J.; Janesko, B. G.; Gomperts, R.; Mennucci, B.; Hratchian, H. P.; Ortiz, J. V.; Izmaylov, A. F.; Sonnenberg, J. L.; Williams-Young, D.; Ding, F.; Lipparini, F.; Egidi, F.; Goings, J.; Peng, B.; Petrone, A.; Henderson, T.; Ranasinghe, D.; Zakrzewski, V. G.; Gao, J.; Rega, N.; Zheng, G.; Liang, W.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Throssell, K.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Keith, T.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Millam, J. M.; Klene, M.; Adamo, C.; Cammi, R.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Farkas, O.; Foresman, J. B.; Fox, D. J. Gaussian 09, Revision D.01; Gaussian, Inc.: Wallingford, 2013.
Daina, A.; Michielin, O.; Zoete, V. Sci. Rep. 2017, 7, 42717.
Pires, D. E. V.; Blundell, T. L.; Ascher, D. B. J. Med. Chem. 2015, 58, 4066.
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Published in Khimiya Geterotsiklicheskikh Soedinenii, 2023, 59(1/2), 80–87
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Kuzu, E., Kuzu, B. Tandem Synthesis of Novel thiazole-substituted pyrrolo[1,2-d][1,2,4]triazin-4(3H)-one Derivatives and their Theoretical Pharmacokinetic Profiles. Chem Heterocycl Comp 59, 80–87 (2023). https://doi.org/10.1007/s10593-023-03165-3
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DOI: https://doi.org/10.1007/s10593-023-03165-3