Synthesis of some new 5-amino-3-(substituted-amino)-6-(fluoro/ nitro)aryl-1,2,4-triazine derivatives as lamotrigine analogs and their evaluation in vitro as antibacterial agents

Authors

  • Abdulrahman Salim Alharbi Department of Chemistry, Faculty of Science, King Abdul Aziz University, Jeddah, Saudi Arabia
  • Nawaa Ali Alshammari Department of Chemistry, Faculty of Science, Northern Borders University, Rafha, Saudi Arabia

DOI:

https://doi.org/10.13171/mjc861907296asa

Abstract

Some new fluorine-substituted 3,5-disubstituted amino-1,2,4-triazines have been obtained from aryl-amination of 2,2,2-trifluoro-N-[2-(5-hydroxy-3-thioxo-2,3-dihydro-1,2,4-triazin-6-yl)-4-nitrophenyl] acetamide followed by ammonolysis to produce N-(2-(5-amino-3-(arylamino)-1,2,4-triazin-6-yl)-4-nitrophenyl)-2,2,2-trifluoroacetamides which reacted with N-phenylthiourea. The structures of products were deduced from their elemental analysis and spectral measurements. The new lamotrigine analogs were evaluated in vitro as antibacterial. Interestingly, some compounds showed interesting activity against the Bacillus subtilis, Streptococcus faecalis, Micrococcus luteus, and Staphylococcus aureus bacteria.

Author Biography

Abdulrahman Salim Alharbi, Department of Chemistry, Faculty of Science, King Abdul Aziz University, Jeddah, Saudi Arabia

Department of Chemistry

References

- J. M. Zakrzewska, Z. Chaudhry, T. J. Nurmikko, Patton, D. W., Mullens, E. L., Lamotrigine (Lamictal) in refractory trigeminal neuralgia: results from a double-blind placebo-controlled crossover trial. Pain, 1997, 73 (2), 223-230. https://doi.org/10.1016/S0304-3959(97)00104-8.

- M. Rowbotham, N. Harden, B. Stacey,

P. Bernstein, L. Magnus-Miller, For the Gabapentin Postherpetic Neuralgia Study, G. Gabapentin for the treatment of postherpetic neuralgia: A randomized controlled trial. JAMA, 1998, 280(21), 1837-1842. http://dx.doi .org/10.1001/jama.280.21.1837.

- D. R. Goldsmith, A. J. Wagstaff, T. Ibbotson, C. M. Perry. Lamotrigine, Drugs, 2003, 63(19), 2029-2050. https://doi.org/10.2165/00003495-200363190-00009.

- J. R. Calabrese, E. Vieta, M. D. Shelton, Latest maintenance data on lamotrigine in bipolar disorder. Eur. Neuropsychopharm., 2003, 13, 57-66. http://dx.doi.org/10.1016/S0924-977X (03)00079-8.

- J. G. Hardman, L. E. Limburd, A. G. Gilman, The pharmacological basis of therapeutics, 10th ed., New York: McGraw-Hill. ISBN 0-07-135469-7., 2000.

- S. Sweetman, Martindale: The Complete Drug Reference, 35 ed., The pharmaceutical press. In: London, 2007.

- Y. Qian, P. C. Lv, L. Shi, R. Q. Fang, Z.C. Song, H.L. Zhu, Synthesis, antimicrobial activity of lamotrigine and its ammonium derivatives. Journal of Chemical Sciences, 2009, 121(4), 463-470.

- M.S.T. Makki, D.A. Bakhotmah, R.M. Abdel-Rahman, F. M. Aqlan, New route to synthesize fluorine substituted lamotrigine drug analogs as an anti-inflammatory agent. Current Organic Synthesis, 2017, 14, 1-10. http://dx.doi.org/10. 2174/1570179414666170509151123.

- M. S. T. Makki, R. M. Abdel-Rahman, A. S. Alharbi, Synthetic approach for novel fluorine substituted α-amino-phosphonic acids containing 1,2,4-triazin-5-one moiety as antioxidant agents. International Journal of Organic Chemistry, 2018, 8(1), 1-15. https://doi .org/10.4236/ijoc.2018.81001.

- S. Cascioferro, B. Parrino, V. Spanò, A. Carbone, A. Montalbano, P. Barraja, P. Diana, G. Cirrincione, An overview of the recent developments of 1,2,4-triazine derivatives as anticancer compounds. European Journal of Medicinal Chemistry, 2017, 142, 328-375.

- M. S. T. Makki, R. M. Abdel-Rahman, A. S. Alharbi, Synthetic strategies, chemical reactivities and biological activities of 3-thioxo-1,2,4-triazin-5-ones and their derivatives. Mini-Reviews in Organic Chemistry, 2019, 16(4), 308-322.

- S. S. Wazalwar, A. R. Banpurkar, F. Perdih, Aqueous phase synthesis, crystal structure, and biological study of isoxazole extensions of pyrazole-4-carbaldehyde derivatives. Journal of Molecular Structure, 2017, 1150, 258-267.

- F. Gao, T. Wang, J. Xiao, G. Huang, Antibacterial activity study of 1,2,4-triazole derivatives. European Journal of Medicinal Chemistry, 2019, 173, 274-281.

- G. Manjunath, G. Bheemaraju, M. Mahesh,

P. Venkata Ramana, Synthesis of new 5-((2-(substitutedphenoxymethyl)-1H-benzo[d]imidazole-1-yl)methyl)-1,3,4-oxadiazole-2-thiol: A novel class of potential antibacterial and antifungal agents. Annales Pharmaceutiques Françaises, 2015, 73 (6), 452-460.

- S. Saeed, N. Rashid, P. G. Jones, M. Ali,

R. Hussain, Synthesis, characterization and biological evaluation of some thiourea derivatives bearing benzothiazole moiety as potential antimicrobial and anticancer agents. European Journal of Medicinal Chemistry, 2010, 45(4), 1323-1331.

- M. Eweis, S. S. Elkholy, M. Z. Elsabee, Antifungal efficacy of chitosan and its thiourea derivatives upon the growth of some sugar-beet pathogens. International Journal of Biological Macromolecules, 2006, 38 (1), 1-8.

- D. Sriram, P. Yogeeswari, K. Madhu, Synthesis and in vitro antitubercular activity of some 1-[(4-sub)phenyl]-3-(4-{1-[(pyridine-4-carbonyl) hydrazono]ethyl}phenyl)thiourea. Bioorganic and Medicinal Chemistry Letters, 2006, 16 (4), 876-878.

- D. Manna, G. Roy, G. Mugesh, Antithyroid Drugs and Their Analogues: Synthesis, Structure, and Mechanism of Action. Accounts of Chemical Research, 2013, 46(11), 2706-2715.

- A. Saeed, M. N. Mustafa, M. Zain-ul-Abideen, G. Shabir, M. F. Erben, U. Flörke, Current developments in chemistry, coordination, structure and biological aspects of 1-(acyl/aroyl)-3-(substituted)thioureas: advances Continue. Journal of Sulfur Chemistry, 2019, 40 (3), 312-350. https://doi.org/10.1080/174159 93.2018.1551488.

- G. Venkanna, D. Nagender, P. Venkateswarlu, K. Chandra Shekhar, G. Madhusudhan, K. Mukkanti, Process for producing 6-(2,3-dichlorophenyl)-1,2,4-triazine 3,5-diamine (Lamotrigine) and identification, characterization of a new N-methyl impurity. Der Pharma Chemica, 2012, 4(1), 100-105.

- R. M. Abdel-Rahman, Synthesis and anti-human immune virus activity of some new fluorine-containing substituted-3-thioxo-1,2,4-triazin-5-ones. Farmaco., 1991, 46(2), 379-389.

- Atta-ur-Rahman Choudhary, M. I. Thomsen W. J., Bioassay techniques for drug development, Harwood Academic Publishers, The Netherlands, 2001, pp. 16-19.

Downloads

Published

2019-07-28

Issue

Section

Organic Chemistry