Generic placeholder image

Current Organic Synthesis

Editor-in-Chief

ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

Research Article

Synthesis and Anti-Inflammatory Effect of Some More New Fluorinated 3-Substituted Amino/ 3,5-Diamino-1,2,4-Triazine Derivatives as Lamotrigine Analogs

Author(s): Mohammed S.T. Makki, Reda M. Abdel-Rahman and Abdulrahman Salim Alharbi*

Volume 16, Issue 1, 2019

Page: [165 - 172] Pages: 8

DOI: 10.2174/1570179415666181105142247

Price: $65

Abstract

Aim and Objective: It is known that the Lamotrigine drug has anti-inflammatory activity. So it was the goal to prepare similar compounds containing fluorine atoms (fluorine-substituted 3,5-diamino-6-aryl- 1,2,4-triazines) as Lamotrigine drug analogs to evaluate them as an anti-inflammatory.

Materials and Methods: The novel fluorine substituted 3,5-diamino-6-aryl-1,2,4-triazines as new Lamotrigine analogs were prepared via aminolysis and/ or ammonolysis of the corresponding 3-thioxo-6-aryl-1,2,4-triazin- 5-ones in ethanolic media.

Results: All the new targets were deduced upon their elemental analysis and spectral data as well as screened as anti-inflammatory agents, where we found that the fluorinated systems 15 and 9-11 exhibited high and more activity.

Conclusion: Simple routes to synthesize some more novel fluorinated Lamotrigine analogs have been reported. The new targets exhibited high and moderate anti-inflammatory probes. Presence of both amino and CF3 groups caused high biological activities of these compounds were studied.

Keywords: Synthesis, fluorinated diamino-1, 2, 4-triazine, lamotrigine, anti-inflammatory, indomethacin drug, lamotrigine analogs.

Graphical Abstract
[1]
Goldsmith, D.R.; Wagstaff, A.J.; Ibbotson, T.; Perry, C.M. Lamotrigine. Drugs, 2003, 63(19), 2029-2050.
[2]
Calabrese, J.R.; Bowden, C.L.; Sachs, G.; Yatham, L.N.; Behnke, K.; Mehtonen, O-P.; Montgomery, P.; Ascher, J.; Paska, W.; Earl, N. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. J. Clin. Psychiatry, 2003, 64(9), 1013-1024.
[3]
Zakrzewska, J.M.; Chaudhry, Z.; Nurmikko, T.J.; 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.
[4]
Rowbotham, M.; Harden, N.; Stacey, B.; Bernstein, P.; Magnus-Miller, L. for the Gabapentin Postherpetic Neuralgia Study, G. Gabapentin for the treatment of postherpetic neuralgia: A randomized controlled trial. JAMA, 1998, 280(21), 1837-1842.
[5]
Shimizu, M.; Okuzumi, K.; Yoneyama, A.; Kunisada, T.; Araake, M.; Ogawa, H.; Kimura, S. In vitro antiseptic susceptibility of clinical isolates from nosocomial infections. Dermatology, 2002, 204(Suppl. 1), 21-27.
[6]
Fink-Jensen, A. Treatment of psychotic disorders. U.S. Patent 5,914.333, June 22 1999.
[7]
Qian, Y.; Lv, P-C.; Shi, L.; Fang, R-Q.; Song, Z-C.; Zhu, H-L. Synthesis, antimicrobial activity of lamotrigine and its ammonium derivatives. J. Chem. Sci., 2009, 121(4), 463-470.
[8]
Makki, M.; Bakhotmah, D.A.; Abdel-Rahman, R.; Aqlan, F.M. New route to synthesize fluorine substituted lamotrigine drug analogues as an anti-inflammatory agent. Curr. Org. Synth., 2017, 14, 1-10.
[9]
Bourin, M.; Masse, F.; Hascoët, M. Evidence for the activity of lamotrigine at 5-HT1A receptors in the mouse forced swimming test. J. Psychiatry Neurosci., 2005, 30(4), 275-282.
[10]
Cunningham, M.O.; Jones, R.S. The anticonvulsant, lamotrigine decreases spontaneous glutamate release but increases spontaneous GABA release in the rat entorhinal cortex in vitro. Neuropharmacology, 2000, 39(11), 2139-2146.
[11]
Makki, M.S.I.; Abdel-Rahman, R.M.; Khan, K.A. Fluorine substituted 1,2,4-triazinones as potential anti-HIV-1 and CDK2 inhibitors. J. Chem., 2014, 2014, 14.
[12]
Abdel-Rahman, R.M.; Angawi, R.F.; Al-Mehmadi, A.R. Synthesis and biological evaluation of fluorine-substituted pyrazolo [4,3-e][1,2,4]triazines as purine analogs. J. Saudi Chem. Soc., 2017, 21(4), 495-503.
[13]
Abdel-Rahman, R. Synthesis of some new fluorine bearing trisubstituted 3-thioxo-1, 2, 4-triazin-5-ones as potential anticancer agents. FARMACO, 1992, 47(3), 319-326.
[14]
a)Al-Romaizan, A.N.; Makki, M.S.T.; Abdel-Rahman, R.M. Synthesis of New Fluorine/Phosphorus Substituted 6-(2′-Amino Phenyl)-3-Thioxo-1,2,4-Triazin-5(2H, 4H)One and Their Related Alkylated Systems as Molluscicidal Agent as against the Snails Responsible for Bilharziasis Diseases. Inter. J. Org. Chem. , 2014, 4(2), 154-168.
(b)Abdel-Rahman, R.M.; Makki, M.S.; Al-Romaizan, A.N. Synthesis of novel fluorine substituted isolated and fused heterobicyclic nitrogen systems bearing 6-(2′-phosphorylanilido)-1, 2, 4-triazin-5-one moiety as potential inhibitor towards HIV-1 activity. Inter. J. Org. Chem. , 2014, 4(04), 247-268.
[15]
Rees, R.W.A.; Russell, P.B.; Foell, T.J.; Bright, R.E. Antimalarial activities of some 3,5-diamino-as-triazine derivatives. J. Med. Chem., 1972, 15(8), 859-861.
[16]
Winter, C.A.; Risley, E.A.; Nuss, G.W. Anti-inflammatory and antipyretic activities of indomethacin, 1-(p-chlorobenzoyl)-5-methoxy-2-methyl-indole-3-acetic acid. J. Pharmacol. Exp. Ther., 1963, 141(3), 369-376.
[17]
Winter, C.A.; Risley, E.A.; Nuss, G.W. Carrageenin-induced edema in hind paw of the rat as an assay for anti-inflammatory drugs. Proc. Soc. Exp. Biol. Med., 1962, 111(3), 544-547.
[18]
Hitchings, G.; Maggiolo, A.; Russell, P.; Werff, H.V.; Rollo, I. 3, 5-Diamino-AS-triazines as inhibitors of lactic acid bacteria and Plasmodia. J. Am. Chem. Soc., 1952, 74(12), 3200-3201.
[19]
Dalvi, V.H.; Rossky, P.J. Molecular origins of fluorocarbon hydrophobicity. Proc. Natl. Acad. Sci., 2010, 107(31), 13603-13607.
[20]
Dolain, C.; Patwa, A.; Godeau, G.; Barthélémy, P. Nucleic acid based fluorinated derivatives: New tools for biomedical applications. Appl. Sci., 2012, 2(2), 245-259.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy