Synthesis of 3-[2-(1H-imidazol-2-yl)alkyl]-2-thioxo-2,3-dihydroquinazolin-4(1H)-one derivatives
DOI:
https://doi.org/10.14739/2409-2932.2018.3.144579Keywords:
imidazoles, quinazolines, synthesisAbstract
Promising biologically active substances are derivatives of imidazole and quinazoline, which are part of the structure of known antifungal drugs and substances with anti-TB and antimicrobial activity. In addition, it should be noted that information on the synthesis and properties of quinoline derivatives containing a fragment of 2-aminoalkylimidazole is practically absent. Proceeding from this, the issue of developing new preparative methods for the synthesis of quinazoline derivatives with a fragment of 2-aminoalkylimidazole appears.
Aim. Expanding the synthetic potential of 2-aminoalkilimidazoliv, the study of reactivity and synthesis of new derivatives of 3- [2- (1H-imidazole-2-yl) -alkyl] -2-thioxo-2,3-dyhidrohinazolin-4 (1H)-ones.
Materials and methods. Methods of organic synthesis; Physical and physical-chemical methods of analysis of organic compounds (NMR spectroscopy 1H, elemental analysis).
Results. The work analyzes the structures that are most promising as potential antimicrobial agents. For the synthesis of new biologically active compounds, we have chosen the strategy of combining quinazoline fragments with an imidazole residue in one molecule. Such an approach, in our opinion, should contribute to increasing the lipophilic properties of the final molecule, which is one of the key requirements for antimicrobial agents. 3-Substituted 2-thioxoquinazolin-4-one was prepared by reacting 2-(α,β-aminoalkyl) imidazoles and with methyl ester of 2-isothiocyanato-benzoic acid. Control of the formation of reaction products was carried out by TCHX. The structure of the 2-thioxoquinazolin-4-one obtained was confirmed by 1H-NMR spectroscopy. The multiplicity and location of the protons are fully consistent with the proposed structure of the compounds.
Conclusions. The possibility of using new aminoalkylimidazoles derivatives as an amine component in the reaction of heterocyclicization with o-isothiocyanatoester is investigated. The synthesis of 3- [2- (1H-imidazol-2-yl) -alkyl] -2-thioxo-2,3-dihydroquinazolin-4 (1H) -one was synthesized for the first time.
References
Retrieved from http://www.prous.com
Retrieved from http://www.beilstein.com
Vijayakumar, B., Prasanthi, P., Muni Teja, K., Makesh Kumar Reddy, K., Nishanthi, P., Nagendramma, M., & Nishanthi, M. (2013) Quinazoline Derivatives & Pharmacological Activities. International Journal of Medicinal Chemistry & Analysis (IJMCA), 3(1), 10–21.
He, D., Wang, M., Zhao, S., Shu, Y., Zeng, H., Xiao, C., et al. (2017) Pharmaceutical prospects of naturally occurring quinazolinone and its derivatives. Fitoterapia, 119, 136–149. doi: 10.1016/j.fitote.2017.05.001.
Hameed, A., Al-Rashida, M., Uroos, M., Ali, S. A., Arshia, Ishtiaq, M., & Khan KM. (2018) Quinazoline and quinazolinone as important medicinal scaffolds: a comparative patent review (2011–2016). Expert Opin Ther Pat, 28(4), 281–297. doi: 10.1080/13543776.2018.1432596.
Khan, I., Ibrar, A., Ahmed, W., & Saeed, A. (2015). Synthetic approaches, functionalization and therapeutic potential of quinazoline and quinazolinone skeletons: the advances continue. Eur J Med Chem, 27(90), 124–169. doi: 10.1016/j.ejmech.2014.10.084.
Camacho, M. E., Chayah, M., García, M. E., Fernández-Sáez, N., Arias, F., Gallo, M. A., & Carrión, M. D. (2016). Quinazolinones, Quinazolinthiones, and Quinazolinimines as Nitric Oxide Synthase Inhibitors: Synthetic Study and Biological Evaluation. Arch Pharm (Weinheim), 349(8), 638–650. doi: 10.1002/ardp.201600020.
Birhan, Y. S., Bekhit, A. A., & Hymete, A. (2014). Synthesis and antileishmanial evaluation of some 2,3-disubstituted-4(3H)-quinazolinone derivatives. Org Med Chem Lett, 4(1), 1–10. doi: 10.1186/s13588-014-0010-1.
Sahu, A., Kumar, D., & Agrawal, R. K. (2017). Antileishmanial Drug Discovery: Synthetic Methods, Chemical Characteristics, and Biological Potential of Quinazolines and its Derivatives. Antiinflamm Antiallergy Agents Med Chem. 16(1), 3–32. doi: 10.2174/1871523016666170502120210.
Khan, I., Ibrar, A., Abbas, N., & Saeed, A. (2014). Recent advances in the structural library of functionalized quinazoline and quinazolinone scaffolds: synthetic approaches and multifarious applications. Eur J Med Chem, 9(76), 193–244 doi: 10.1016/j.ejmech.2014.02.005.
Sandeep, A., Sandeep, Y., Navneet, A., & Nagori, DR. B.P. (2013). Synthesis and Antimicrobial Activity of Quinazoline Thione Derivatives of Tetralone. Int. J. Inv. Pharm. Sci, 15, 456–461.
Dan, Wang, & Feng, Gao. (2013) Quinazoline derivatives: synthesis and bioactivities. Chemistry Central Journal, 7, 95. doi: 10.1186/1752-153X-7-95
PASS Online. Retrieved from http://www.pharmaexpert.ru/passonline
Tkachenko, E. V., Vlasov, S. V., Zhuravel' I. A., et al. (2013) Sintez i protivomikrobnaya aktivnost' 2-alkiltio-3-N-zameshhennykh tieno[3,2-d]pirimidin-4(3H)-onov. Nauchnye vedomosti BelGU. Medicina Farmaciya, 25(168), 24/1, 131–138. [in Russian].
Borysov, O. V., Zavada, O. O., Zhuravel, I. O., & Kovalenko, S. M. (2013) Strukturna modyfikatsiia aminokyslot: syntez 2-(α,β,ω-aminoalkil)imidazoliv [Structural modification of amino acids: synthesis of 2-(α,β,ω-aminoalkyl) imidazoles]. Zhurnal orhanichnoi ta farmatsevtychnoi khimii, 11, 1(41), 66–69. [in Ukrainian].
Downloads
How to Cite
Issue
Section
License
Authors who publish with this journal retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
