SYNTHESIS OF 2-FLUOROBENZOYL THIOUREA DERIVATIVES

Year 2023, Volume: 22 Issue: 44, 417 - 424, 31.12.2023

Şule Erol Günal

https://doi.org/10.55071/ticaretfbd.1364818

Cited By: 1

Abstract

Fluorine-containing compounds play a significant role in drug development because fluorine atom has unique chemical properties due to its high electronegativity which significantly influences the properties important for drug design. In the present study, 2-fluorobenzoyl thiourea derivatives were synthesized by the reaction of 2-fluorobenzoyl isothiocyanate, which was obtained by the reaction of 2-fluorobenzoyl chloride with ammonium thiocyanate, with appropriate aniline derivatives. The structures of the benzoyl thioureas were confirmed by IR, 1H and 13C NMR spectroscopy.

Keywords

Benzoyl thioureas, fluorinated compounds, thioureas

2-FLOROBENZOİL TİYOÜRE TÜREVLERİNİN SENTEZİ

Abstract

Flor içeren bileşikler ilaç geliştirmede önemli bir rol oynar çünkü flor atomu, ilaç tasarımı için önemli olan özellikleri önemli ölçüde etkileyen yüksek elektronegatifliği nedeniyle benzersiz kimyasal özelliklere sahiptir. Bu çalışmada, 2-florobenzoil klorürün amonyum tiyosiyanat ile reaksiyonu sonucu elde edilen 2-florobenzoil izotiyosiyanatın uygun anilin türevleri ile reaksiyonu sonucu bir dizi 2-florobenzoil tiyoüre türevi sentezlendi. Benzoil tiyoüre yapıları IR, 1H ve 13C NMR spektroskopisi ile doğrulandı.

Keywords

Tiyoüreler, Benzoil tiyoüreler, florlu bileşikler

References

• Agola, J.O., Hong, L., Surviladze, Z., Ursu, O., Waller, A., Strouse J.J., Simpson, D.S., Schroeder, C.E., Oprea, T.I., Golden, J.E., Aubé, J., Buranda, T., Sklar, L. A. & Wandinger-Ness, A. (2012). A Competitive Nucleotide Binding Inhibitor: In Vitro Characterization of Rab7 GTPase Inhibition. ACS Chemical Biology. 7(6), 1095–1108. https://doi.org/10.1021/cb3001099.
• Ali, S. &. Zhou, J. (2023). Highlights on U.S. FDA-approved fluorinated drugs over the past five years (2018–2022). European Journal of Medicinal Chemistry. 256, 115476. https://doi.org/10.1016/j.ejmech.2023.115476.
• Ekoue-Kovi, K., Yearick, K., Iwaniuk, D. P., Natarajan, J.K., Alumasa, J., de Dios, A.C., Roepe P.D. & Wolf. C. (2009). Synthesis and antimalarial activity of new 4-amino-7-chloroquinolyl amides, sulfonamides, ureas and thioureas. Bioorganic and Medicinal Chemistry. 17(1). 270–283. https://doi.org/10.1016/j.bmc.2008.11.009.
• Han, J., Remete, A. M., Dobson, L. S., Kiss, L., Izawa, K., Moriwaki, H., Soloshonok, V.A. & O’Hagan, D. (2020). Next generation organofluorine containing blockbuster drugs. Journal of Fluorine Chemistry. 239, 109639. https://doi.org/10.1016/j.jfluchem.2020.109639.
• Hroch, L., Guest, P., Benek, O., Soukup, O., Janockova, J., Dolezal, R., Kuca, K., Aitken, L., Smith, T.K., Gunn-Moore, F., Zala, D., Ramsay, R.R. & Musilek, K. (2017). Synthesis and evaluation of frentizole-based indolyl thiourea analogues as MAO/ABAD inhibitors for Alzheimer’s disease treatment. Bioorganic and Medicinal Chemistry. 25(3), 1143-1152. https://doi.org/10.1016/j.bmc.2016.12.029.
• Karipcin, F., Atis, M., Sariboga, B., Celik, H. & Tas. M. (2013). Structural, spectral, optical and antimicrobial properties of synthesized 1-benzoyl-3-furan-2-ylmethyl-thiourea. Journal of Molecular Structure. 1048, 69–77. https://doi.org/10.1016/j.molstruc.2013.05.042.
• Lain, S., Hollick, J.J., Campbell, J., Staples, O.D., Higgins, M., Aoubala, M., McCarthy, A.R., Appleyard, V., Murray, K.E., Baker, L., Thompson, A., Mathers, J., Holland, S.J., Stark, M.J., Pass, G., Woods, J., Lane, D.P. & Westwood N.J. (2008). Discovery, In Vivo Activity, and Mechanism of Action of a Small-Molecule p53 Activator. Cancer Cell. 13(5), 454-463. https://doi.org/10.1016/j.ccr.2008.03.004.
• Liav, A., Angala, S. K., Brennan, P. J.& Jackson, M. (2008). N-D-Aldopentofuranosyl-N-[p-(isoamyloxy)phenyl]-thiourea derivatives: potential anti-TB therapeutic agents. Bioorganic and Medicinal Chemistry Letters. 18(8), 2649–2651. https://doi.org/10.1016/j.bmcl.2008.03.033.
• Manjula, S.N., Noolvi N. M., Parihar, K. V., Manohara Reddy, S.A., Ramani, V., Gadad, A.K., Singh, G., N.G. Kutty & Rao, C.M. (2009). Synthesis and antitumor activity of optically active thiourea and their 2-aminobenzothiazole derivatives: a novel class of anticancer agents. European Journal of Medicinal Chemistry. 44(7), 2923–2929. https://doi.org/10.1016/j.ejmech.2008.12.002.
• McCarthy, A.R., Pirrie, L., Hollick, J.J., Ronseaux, S., Campbell, J., Higgins, M., Staples, O.D., Tran, F., Slawin, A.M.Z., Lain, S. & Westwood, N. J. (2012). Synthesis and biological characterisation of sirtuin inhibitors based on the tenovins. Bioorganic and Medicinal Chemistry. 20(5), 1779–1793. https://doi.org/10.1016/j.bmc.2012.01.001.
• Muhammad M., Khan, S., Shehzadi S. A., Gul Z., Al-Saidi, H.M., Kamran, A.W., Alhumaydhi F.A. (2022). Recent advances in colorimetric and fluorescent chemosensors based on thiourea derivatives for metallic cations: A review. Dyes and Pigments, 205, 110477. https://doi.org/10.1016/j.dyepig.2022.110477.
• O’Hagan, D. (2010). Fluorine in health care: Organofluorine containing blockbuster drugs. Journal of Fluorine Chemistry. 131(11), 1071–1081. https://doi.org/10.1016/j.jfluchem.2010.03.003.
• Rizzo, C., Amata, S., Pibiri, I., Pace, A., Buscemi S. & Piccionello, A. P. (2023). FDA-Approved Fluorinated Heterocyclic Drugs from 2016 to 2022. International Journal of Molecular Sciences. 24(9), 7728. https://doi.org/10.3390/ijms24097728.
• Seo, H., Kohlbrand, A.J., Stokes, R.W., Chung, J., Cohen, S.M. (2023). Masking thiol reactivity with thioamide, thiourea, and thiocarbamate-based MBPs. Chem. Commun., 59(16), 2283–2286. https://doi.org/10.1039/D2CC06596G.
• Shah, P. & Westwell, A. D. (2007). The role of fluorine in medicinal chemistry. Journal of Enzyme Inhibition and Medicinal Chemistry, 22(5), 527–540. https://doi.org/10.1080/14756360701425014.
• Teke -Tuncel, S., Erol-Gunal, S., Ekizoglu M., Gokhan-Kelekci, N., Erdem, S.S., Bulak E., Frey W., Dogan, I. (2019). Thioureas and their cyclized derivatives: Synthesis, conformational analysis and antimicrobial evaluation. Journal of Molecular Structure. 1179, 40-56. https://doi.org/10.1016/j.molstruc.2018.10.055.
• Tsogoeva, S.B., Hateley, M.J., Yalalov, D.A., Meindl, K., Weckbecker, C. & Huthmacher, K. (2005). Thiourea-based non-nucleoside inhibitors of HIV reverse transcriptase as bifunctional organocatalysts in the asymmetric Strecker synthesis. Bioorganic and Medicinal Chemistry. 13(19), 5680–5685. https://doi.org/10.1016/j.bmc.2005.05.014.