Cage-like amines with norbornane and adamantane frameworks were studied in a versatile, convenient one-pot green synthetic experiment for pyrimidine core annulation via cleavage of a 1H-tetrazole ring. The transannulation was performed without an excess of the reagents and solvent under optimized conditions. As a result, 11 new thieno[2,3-d]pyrimidinones with bulky substituents were obtained in high yields without the need of further purification and with excellent selectivity of the process. The introduced сage-like framework is regarded as a bioisostere of the 2-arylamino moiety. Preliminary screening of the biological activity was performed and 2-{[1-(bicyclo[2.2.1]heptan-2-yl)ethyl]amino}-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one demonstrated high toxicity toward human leukemia HL-60, cervix carcinoma KB3-1, and colon carcinoma HCT116 cells that correlates well with the results obtained previously for the activity of the compounds with benzylamino substituents.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Stockdale, T. P.; Williams, C. M. Chem. Soc. Rev. 2015, 44, 7737.
Liu, J.; Obando, D.; Liao, V.; Lifa, T.; Codd R. Eur. J. Med. Chem. 2011, 46, 1949.
Mykhailiuk, P. K. Org. Biomol. Chem. 2019, 17, 2839.
(a) Tkachenko, I. V.; Tarabara, I. N.; Omelchenko, I. V.; Palchykov, V. A. J. Heterocycl. Chem. 2018, 55, 2381. (b) Kas'yan, L. I.; Prid'ma, S. A.; Turov, A. V.; Pal'chikov, V. A.; Kas'yan, A. O.; Karat, L. D. Russ. J. Org. Chem. 2009, 45, 505. [Zh. Org. Khim. 2009, 45, 520.] (c) Kasyan, L. I.; Sereda, S. V.; Potekhin, K. A.; Kasyan, A. O. Heteroat. Chem. 1997, 8, 177. c Pokhodylo, N. T.; Matiichuk, V. S.; Obushak, M. D. Russ. J. Org. Chem. 2017, 53, 481. [Zh. Org. Khim. 2017, 53, 470.]
Pokhodylo, N. T.; Matiychuk, V. S.; Obushak, M. D. Tetrahedron 2008, 64, 1430.
Pokhodylo, N. T.; Shyyka, O. Ya.; Matiychuk, V. S.; Obushak, M. D. ACS Comb Sci. 2015, 17, 399.
Shyyka, O. Ya.; Pokhodylo, N. T.; Slyvka, Yu. I.; Goreshnik, E. A.; Obushak M. D. Tetrahedron Lett. 2018, 59, 1112.
Obst, M.; König, B. Eur. J. Org. Chem. 2018, 4213.
Molecular Rearrangements in Organic Synthesis; Rojas, C. M., Ed.; Wiley: Hoboken, 2016.
(a) Chattopadhyay, B.; Gevorgyan, V. Angew. Chem., Int. Ed. 2011, 51, 862. (b) Sebris, A.; Turks, M. Chem Heterocycl. Compd. 2019, 55, 1041. [Khim. Geterotsikl. Soedin. 2019, 55, 1041.] (c) Khaidarov, A. R.; Rostovskii, N. V.; Starova, G. L.; Khlebnikov, A. F.; Novikov, M. S. Chem. Heterocycl. Compd. 2018, 54, 946. [Khim. Geterotsikl. Soedin. 2018, 54, 946.]
(a) Shyyka, O. Ya.; Pokhodylo, N. T.; Finiuk, N. S. Biopolym. Cell. 2019, 35, 321. (b) Pokhodylo, N. T.; Shyyka, O. Ya.; Tupychak, M. A.; Obushak, M. D. Chem. Heterocycl. Compd. 2018, 54, 209. [Khim. Geterotsikl. Soedin. 2018, 54, 209.]
Shyyka, O.; Pokhodylo, N.; Finiuk, N.; Matiychuk, V.; Stoika, R.; Obushak, M. Sci. Pharm. 2018, 86(3), 28.
Sokolova, A. S.; Yarovaya, О. I.; Baev, D. S.; Shernyukov, А. V.; Shtro, A. A.; Zarubaev, V. V.; Salakhutdinov, N. F. Eur. J. Med. Chem. 2017, 127, 661.
Tandura, S. N.; Shumsky, A. N.; Litvin, E. F.; Kozlova, L. M.; Shuvalova, E. V.; Sharf, V. Z.; Kolesnikov, S. P. Russ. Chem. Bull., Int. Ed. 2001, 50, 1014.
Liu, X.; Zu, Y.; Fu, Y.; Yao, L.; Gu, C.; Wang, W.; Efferth, T. Eur. Food Res. Technol. 2009, 229, 247.
Author information
Authors and Affiliations
Corresponding author
Additional information
Published in Khimiya Geterotsiklicheskikh Soedinenii, 2020, 56(6), 793–799
Electronic supplementary material
ESM 1
(PDF 4831 kb)
Rights and permissions
About this article
Cite this article
Shyyka, O.Y., Pokhodylo, N.T., Palchykov, V.A. et al. Cage-Like Amines in the Green Protocol of Transannular Thieno[2,3-d]Pyrimidinone Formation as Promising Anticancer Agents. Chem Heterocycl Comp 56, 793–799 (2020). https://doi.org/10.1007/s10593-020-02732-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10593-020-02732-2