Skip to content
BY-NC-ND 3.0 license Open Access Published by De Gruyter Open Access July 21, 2012

α-Amino acid-derived 2-phenylimidazoles with potential antimycobacterial activity

  • Daniel Cvejn EMAIL logo , Věra Klimešová and Filip Bureš
From the journal Open Chemistry


α-Amino acid-derived 2-phenylimidazole derivatives were designed, synthesized, and further investigated as potential antimycobacterial agents. The synthesis of target imidazole derivatives involved the transformation of Cbz-protected α-amino acids (Ala, Val, Phe, Leu, iLe, and Pro) into α-diazoketones and α-bromoketones, respectively. Subsequent treatment of α-bromoketones with (4-nitro)benzamidine afforded imidazole derivatives bearing α-amino acid residue appended to the imidazole C4 and (4-nitro)phenyl ring in the position C2. Antimycobacterial activities of both series of compounds against M. tuberculosis, M. avium, and M. kansasii were screened and basic structure-activity relationships were further evaluated.

[1] S. T. Cole, G. Riccardi, Curr. Opin. Microbiol. 14, 570 (2011) in Google Scholar PubMed

[2] D.E. Griffith, T. Aksamit, B.A. Brown-Elliott, A. Catanzaro, C. Daley, F. Gordin, S.M. Holland, R. Horsburgh, G. Huitt, M.F. Iademarco, M. Iseman, K. Olivier, S. Ruoss, C.F. von Reyn, R.J. Wallace Jr., K. Winthrop, Am. J. Resp. Crit. Care, 175, 367 (2007) in Google Scholar PubMed

[3] L. Ballel, R.A. Field, K. Duncan, R.J. Young, Antimicrob. Agents Chemother. 49, 2153 (2005) in Google Scholar PubMed PubMed Central

[4] R.J. O’Brien, M. Spigelman, Clin. Chest. Med. 26, 327 (2005) in Google Scholar PubMed

[5] M. Krátký, J. Vinšová, Chem. Listy 104, 998 (2010) Search in Google Scholar

[6] M. Biava, G.C. Porretta, G. Poce, A. De Logu, R. Meleddu, E. De Rossi, F. Manetti, M. Botta, Eur. J. Med. Chem. 44, 4734 (2009) in Google Scholar PubMed

[7] D. Deidda, G. Lampis, R. Fioravanti, M. Biava, G.C. Porretta, S. Zanetti, R. Pompei, Antimicrob. Agents Chemother. 42, 3035 (1998) 10.1128/AAC.42.11.3035Search in Google Scholar PubMed PubMed Central

[8] A. Lilienkampf, M. Pieroni, B. Wan, Y. Wang, S.G. Franzblau, A.P. Kozikowski, J. Med. Chem. 53, 678 (2010) in Google Scholar PubMed

[9] G. Navarrete-Vázquez, G.M. Molina-Salinas, Z.V. Duarte-Fajardo, J. Vargas-Villarreal, S. Estrada-Soto, F. Gonzáles-Salazar, E. Hernández-Núñez, S. Said-Fernández, Bioorg. Med. Chem. 15, 5502 (2007) in Google Scholar PubMed

[10] M. Boiani, M. González, Mini-Rev. Med. Chem. 5, 409 (2005) in Google Scholar PubMed

[11] L. De Luca, Curr. Med. Chem. 13, 1 (2006) in Google Scholar

[12] F. Bellina, S. Cauteruccio, R. Rossi, Tetrahedron 63, 4571 (2007) in Google Scholar

[13] B. Dolensky, G. Nam, W.-P. Deng, J. Narayanan, J. Fan, K. L. Kirk, J. Fluorine Chem. 125, 501 (2004) in Google Scholar

[14] C.K. Stover, P. Warrener, D.R. VanDevanter, D.R. Sherman, T.R. Arain, M.H. Langhorne, S.W. Anderson, J.A. Towell, Y. Yuan, D.N. McMurray, B.N. Kreiswirth, C.E. Barry, W.R. Baker, Nature 405, 962 (2000) in Google Scholar PubMed

[15] M. Matsumoto, H. Hashizume, T. Tomishige, M. Kawasaki, H. Tsubouchi, H. Sasaki, Y. Shimokawa, M. Komatsu, PLoS Med. 3, 2131 (2006) in Google Scholar PubMed PubMed Central

[16] P. Pařík, J. Jansa, S. Holešová, A. Marek, V. Klimešová, J. Heterocyclic Chem., accepted (2012) Search in Google Scholar

[17] O. Pytela, V. Klimešová, Chem. Pharm. Bull. 59, 179 (2011) in Google Scholar PubMed

[18] W.O. Foye, T.L. Lemke, D.A. Williams, Foye’s principles of medicinal chemistry, 6th edition (Lippincott Williamsїlkins, a Wolters Kluwer, Baltimore, 2008) Search in Google Scholar

[19] F. Bureš, J. Kulhánek, Tetrahedron:Asymmetry 16, 1347 (2005) in Google Scholar

[20] F. Bureš, T. Szotkowski, J. Kulhánek, O. Pytela, M. Ludwig, M. Holčapek, Tetrahedron: Asymmetry 17, 900 (2006) in Google Scholar

[21] A. Marek, J. Kulhánek, M. Ludwig, F. Bureš, Molecules 12, 1183 (2007) in Google Scholar PubMed PubMed Central

[22] A. Marek, J. Kulhánek, F. Bureš, Synthesis 325 (2009) Search in Google Scholar

[23] A. Marek, J. Kulhánek, W. B. Schweizer, F. Bureš, Synthesis 3188 (2010). 10.1055/s-0030-1258183Search in Google Scholar

[24] F. Bureš, PhD thesis (University of Pardubice, Pardubice, Czech Republic, 2005) Search in Google Scholar

[25] F.C. Schaefer, G.A. Peters, J. Org. Chem. 26, 412 (1961) in Google Scholar

[26] A.R. Katritzky, A.F. Pozharskii, Handbook of heterocyclic chemistry, 2nd edition (Elsevier Science Ltd, Oxford, 2000) Search in Google Scholar

Published Online: 2012-7-21
Published in Print: 2012-10-1

© 2012 Versita Warsaw

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Downloaded on 6.12.2023 from
Scroll to top button