European Journal of Chemistry

Synthesis and pharmacological evaluation of new fluorine substituted pyrimido[1,2-b][1,2,4]triazines and [1,3,5]-triazino-[1,2-b][1,2,4]triazines derived as CDK2 potential inhibitors

Article Sidebar

PDF
Published: Sep 30, 2020
DOI: https://doi.org/10.5155/eurjchem.11.3.198-205.1988
Keywords:
Synthesis, 1, 2, 4-Triazine, Pyrimido-[1, 2-b]-[1, 4]triazine, [1, 3, 5]-Triazino[1, CDK2 enzymatic inhibitors evaluation, Fluorinated fused heterocyclic systems
Section
Research Article
Issue
Vol. 11 No. 3 (2020): September 2020
Dates
Received 2020-04-04
Accepted 2020-05-29
Published 2020-09-30
Crossmark


Main Article Content

Dina Bakhotmah
Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, 21551, Saudi Arabia
http://orcid.org/0000-0001-6651-7932
Fatimah Alotaibi
Department of Chemistry, Faculty of Science, Tabuk University, Tabuk, 71941, Saudi Arabia
http://orcid.org/0000-0003-2417-7735

Abstract

New fluorine-substituted polyfunctional pyrimido-[1,2-b]-[1,2,4]triazines and [1,3,5]-triazino[1,2-b]-[1,2,4]triazines were synthesized via the reaction between 3-amino-6-(2-aminophenyl)-1,2,4-triazin-5(2H)-one with polyfunctional oxygen/sulfur/nitrogen reagents under different conditions. Structures of the target compounds were deduced by elemental analysis and spectral measurements (IR, 1H/13C NMR, and mass spectra). According to the obtained inhibitor assay results, the inhibition activity of the new fluorine-substituted 1,2,4-triazines toward CDK2 decreased in the order of compounds 3 > 8 > 9 > 6 > 13 > 15.


icon graph This Abstract was viewed 1470 times | icon graph Article PDF downloaded 727 times

How to Cite
(1)
Bakhotmah, D.; Alotaibi, F. Synthesis and Pharmacological Evaluation of New Fluorine Substituted pyrimido[1,2-b][1,2,4]triazines and [1,3,5]-Triazino-[1,2-b][1,2,4]triazines Derived As CDK2 Potential Inhibitors. Eur. J. Chem. 2020, 11, 198-205.

Article Details

Share
Links for Article


Crossref - Scopus - Google - European PMC
Crossref
Scopus
Google Scholar
Europe PMC
References

[1]. Abdel-Rahman, R. M.; Angawi, R. F.; Al-Mehmadi, A. R. J. Saudi Chem. Soc. 2017, 21(4), 495-503
https://doi.org/10.1016/j.jscs.2016.11.004

[2]. Bakhotmah, D. A. Polycycl. Aromat. Comp. 2019, in press, DOI: 10.1080/10406638.2019.1625066
https://doi.org/10.1080/10406638.2019.1625066

[3]. Abdel-Rahman, R. M.; Alharbi, A. S.; Alshammari, N. A.; Adnan, Y. O. Lett. Org. Chem. 2020, 17(3), 184-190.
https://doi.org/10.2174/1570178616666190718120953

[4]. Makki, M. S.; Abdel-Rahman, R. M.; Alharbi, A. S. Curr. Org. Synth. 2019, 16(1), 165-172.
https://doi.org/10.2174/1570179415666181105142247

[5]. Makki, M. S.; Dina, A. B.; Abdel-Rahman, R. M.; Aqlan, F. M. Curr. Org. Synth. 2018, 15(1), 116-125.
https://doi.org/10.2174/1570179414666170509151123

[6]. Tib, L. A.; Adibani, S. A. Int. J. Org. Chem. 2018, 8, 176-189.
https://doi.org/10.4236/ijoc.2018.81013

[7]. Makki, M. S. T.; Abdel-Rahman, R. M.; Ali, O. A. A. Asian. J. Chem. 2016, 28(4), 917-920.
https://doi.org/10.14233/ajchem.2016.19555

[8]. Makki, M. S.; Abdel-Rahman, R. M.; Aqlan, F. M. Int. J. Org. Chem. 2015, 5(3), 200-211.
https://doi.org/10.4236/ijoc.2015.53020

[9]. Makki, M. S.; Abdel-Rahman, R. M.; Khan, K. A. J. Chem. 2014, 430573, 1-14.
https://doi.org/10.1155/2014/430573

[10]. Al-Romaizan, A. N. Mediterr. J. Chem. 2019, 9(3), 249-257.
https://doi.org/10.13171/mjc93191014920aar

[11]. Aqlan, F. M.; Makki, M. S.; Abdel‐Rahman, R. M. J. Heterocyclic. Chem. 2016, 53(4), 1310-1317.
https://doi.org/10.1002/jhet.2386

[12]. Abdel-Rahman, R. M.; Makki, M. S.; Bawazir, W. A. J. Chem. 2011, 8(1), 405-414.
https://doi.org/10.1155/2011/586063

[13]. Leyla, Y. L.; Demirayak, S.; Ilgin, S.; Atli, O. Bioorg. Med. Chem. 2014, 22, 6313-6323.
https://doi.org/10.1016/j.bmc.2014.10.002

[14]. Abdel-Rahman, R. M. Farmaco 1992, 47(3), 319-326.
https://doi.org/10.1007/BF02137667

[15]. Tomachin, A. B.; Krylova, I. Zh. Org. Khim. 1986, 22, 2420-2434.

[16]. Abdel-Rahman, R. M.; Morsy, J. M.; Hanafy, F.; Amene, H. A. Pharmazie 1999, 54(9), 667-671.

[17]. Abdel-Rahman, R. M. Pharmazie 2001, 56, 18-22.

[18]. Krystof, V.; Cankar, P.; Frysova, I.; Slouka, J.; Kontopidis, G.; Dzubak, P.; Hajduch, M.; Srovnal, J.; de Azevedo, W. F.; Orsag, M.; Paprskarova, M.; Rolcik, J.; Latr, A.; Fischer, P. M.; Strnad, M. J. Med. Chem. 2006, 49(22), 6500-6509.
https://doi.org/10.1021/jm0605740

[19]. Gucky, T.; Reznickova, E.; Dzubak, P.; Hajduch, M.; Krystof, V. Monatsh. Chemie-Chem. Monthly 2010, 141(6), 709-714.
https://doi.org/10.1007/s00706-010-0314-4

[20]. Lazzaro, F.; Giannattasio, M.; Puddu, F.; Granata, M.; Pellicioli, A.; Plevani, P.; Muzi-Falconi, M. DNA Repair 2009, 8(9), 1055-1067.
https://doi.org/10.1016/j.dnarep.2009.04.022

[21]. Wohlbold, L.; Fisher, R. P. DNA Repair 2009, 8(9), 1018-1024.
https://doi.org/10.1016/j.dnarep.2009.04.009

[22]. Saloutina, L. V.; Zapevalov, A. Y.; Kodess, M. I.; Slepukhin, P. A.; Ganebnykh, I. N.; Saloutin, V. I.; Chupakhin, O. N, J. Fluorine Chem. 2019, 227, 109362, 1-9.
https://doi.org/10.1016/j.jfluchem.2019.109362

[23]. Isanbor, C.; O'Hagan, D. J. Fluorine Chem. 2006, 127, 303-319.
https://doi.org/10.1016/j.jfluchem.2006.01.011

[24]. Abdel-Rahman, R. M.; Abdel-Monem, W. R. Indian J. Chem. B 2007, 46, 838-846.

[25]. Abdel-Rahman, R. M.; Abdel-Monem, W. R. Int. J. Chem. 2006, 16, 1-14.

[26]. Javid, A.; Heravi, M. M.; Bamoharram, F.; Nikpour, M. J. Chem. 2011, 8(2), 547-552.
https://doi.org/10.1155/2011/980546

[27]. Abrahams, S. L.; Hazen, R. J.; Batson, A. G.; Phillips, A. P. J. Pharmacol. Exp. Ther. 1989, 249(2), 359-365.

[28]. Tanigawara, Y.; Aoyama, N.; Kita, T.; Shirakawa, K.; Komada, F.; Kasuga, M.; Okumura, K. Clin. Pharmacol. Ther. 1999, 66(5), 528-534.
https://doi.org/10.1016/S0009-9236(99)70017-2

[29]. Chowdhury, S.; Mohan, R. S.; Scott, J. L. Tetrahedron 2007, 63(11), 2363-2389.
https://doi.org/10.1016/j.tet.2006.11.001

[30]. Wolkenberg, S. E.; Wisnoski, D. D.; Leister, W. H.; Wang, Y.; Zhao, Z.; Lindsley, C. W. Org. Lett. 2004, 6(9), 1453-1456.
https://doi.org/10.1021/ol049682b

[31]. Abdel-Rahman, R. M.; El-Gendy, Z. Indian. J. Chem. B 1989, 28, 1072-1076.

[32]. Jindal, A.; Pandya, K.; Khan, I. Med. J. Armed Forces India 2015, 71(2), 178-181.
https://doi.org/10.1016/j.mjafi.2014.04.011

[33]. Tsvetkova, E.; Goss, G. Curr. Oncol. 2012, 19(Suppl 1), S45 -S51.

[34]. Maeda, H.; Khatami, M. Clin. Trans. Med. 2018, 7(1), 11-11.

[35]. Okasha, R. M.; Alsehli, M.; Ihmaid, S.; Althagfan, S. S.; El-Gaby, M. S. A.; Ahmed, H. E. A.; Afifi, T. H. Bioorg. Chem. 2019, 92, 103262, 1-15
https://doi.org/10.1016/j.bioorg.2019.103262

[36]. Roskoski, J, R. Pharmacol. Res. 2019, 139, 471-488.
https://doi.org/10.1016/j.phrs.2018.11.035

[37]. Sanchez-Martinez, C.; Lallena, M. J.; Sanfeliciano, S. G.; de Dios, A. Bioorg. Med. Chem. Lett. 2019, 29(20), 126637, 1-18.
https://doi.org/10.1016/j.bmcl.2019.126637

[38]. Liu, Q.; Gao, J.; Zhao, C.; Guo, Y.; Wang, S.; Shen, F.; Xing, X.; Luo, Y. DNA Repair 2020, 85, 102702, 1-15.
https://doi.org/10.1016/j.dnarep.2019.102702

[39]. Matthews, D. J.; Gerritsen, M. E., Targeting Protein kinases for Cancer Therapy, John Wiley & Sons Inc., Hoboken, New Jersey, 2010.
https://doi.org/10.1002/9780470555293

[40]. Senderowicz, A. M., Inhibitors of cyclin-dependent kinase modulators for cancer therapy, In Advances in Targeted Cancer Therapy, Springer, 2005.
https://doi.org/10.1201/9781420005400.ch8

[41]. Chandrappa, S.; Kavitha, C. V.; Shahabuddin, M. S.; Vinaya, K.; Ananda Kumar, C. S.; Ranganatha, S. R.; Raghavan, S. C.; Rangappa, K. S. Bioorg. Med. Chem. 2009, 17(6), 2576-2584.
https://doi.org/10.1016/j.bmc.2009.01.016

[42]. Bakhotmah, D. A. Am. J. Heterocyclic. Chem. 2019, 5(4), 76-80.

Supporting Agencies

Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, 21551, Saudi Arabia.
Most read articles by the same author(s)
TrendMD

Dimensions - Altmetric - scite_ - PlumX

Downloads and views

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...
License Terms

License Terms

by-nc

Copyright © 2025 by Authors. This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at https://www.eurjchem.com/index.php/eurjchem/terms and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0). By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution, or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License (https://www.eurjchem.com/index.php/eurjchem/terms) are administered by Atlanta Publishing House LLC (European Journal of Chemistry).