Synthetic Strategies, Chemical Reactivities and Biological Activities of 3-Thioxo-1,2,4-Triazin-5-Ones and Their Derivatives

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

Journal Name: Mini-Reviews in Organic Chemistry

Volume 16 , Issue 4 , 2019


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

In recent years, a very interest in the synthesis of functionalized 3-thioxo-1,2,4-triazin-5- ones and their derivatives as vital probes has been increased, due to the important, applications of the medicinal, pharmacological, and biological field as a drug, semi drug, and bioactive systems. The present work review outlines extensive recent advances literature survey on the synthesis of sulfurbearing 1,2,4-triazin-5-one derivatives has been reconsidered. Also, the behavior of these family towards electrophilic and nucleophilic reagents in different media and conditions reported. The biological evaluation of the most synthesized systems included anticancer, anti-HIV, antimicrobial as well as their enzymatic effects (cellobiase produced by fungi) have been reported. The reactivity of these systems depends on the polarity of solvent, temperature, molarity as well as a type of tautomeric present.

Keywords: 3-Thioxo-1, 2, 4-triazin-5-one, anti-HIV, biocidal effects, cytotoxicity, α-ketoesters, Sulfur compounds, thioxotriazinone.

[1]
Abdel-Rahman, R.M. Chemistry of uncondensed 1,2,4-triazines part-II sulfur-containing 5-oxo-1,2,4-triazin-3-yl moiety an overview. Phosphorus Sulfur Silicon Relat., 2000, 166, 315-357.
[2]
Abdel-Rahman, R.M.; Makki, M.S.T.; Bawzir, W.A. Synthesis of fluorine heterocyclic nitrogen systems derived from sulfa drugs as photochemical probe agents for inhibition of vitiligo disease-part II. E-J. Chem., 2010, 7(S1), S93-S102.
[3]
Abdel-Rahman, R.M.; Makki, M.S.T.; Bawzir, W.A. Synthesis of some more fluorine heterocyclic nitrogen systems derived from sulfa drugs as photochemical probe agents for inhibition of vitiligo disease-part I. E-J. Chem., 2011, 8(1), 405-414.
[4]
Abdel-Rahman, R.M.; Makki, M.S.T.; Ali, T.E.; Ibrahim, M.A. 1,2,4-Triazine chemistry part III: Synthetic strategies functionalized bridgehead nitrogen heteroannulated 1,2,4-triazines system and their regiospecific and pharmacological properties. Curr. Org. Synth., 2013, 10(1), 136-160.
[5]
Makki, M.S.T.; Abdel-Rahman, R.M.; Abdu Ali, O.A. Synthesis of new fluorinated 1,2,4-triazino[3,4-b][1,3,4]thiadiazolones as antiviral probes-part II reactivities of fluorinated 3-aminophenyl-1,2,4-triazinothiadiazolone. Inter. J. Org. Chem., 2015, 5(3), 153-165.
[6]
Abdel-Rahman, R.M. Synthesis and anti-human immune virus some new fluorine-containing substituted-3-thioxo-1,2,4-triazin-5-ones. IL Farmaco, 1991, 46(2), 379-389.
[7]
Abdel-Rahman, R.M. Synthesis of some new fluorine bearing trisubstituted 3-thioxo-1,2,4- triazin-5-ones as potential anticancer agents. IL Farmaco, 1992, 47(3), 319-326.
[8]
Makki, M.S.T.; Abdel-Rahman, R.M.; Khan, K.A. Fluorine substituted 1,2,4-triazinones as potential anti-HIV-1 and CDK2 inhibitors. J. Chem., 2014, 430573, 14.
[9]
Abdel-Rahman, R.M.; Makki, M.S.T.; 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, 247-268.
[10]
Abdel-Rahman, R.M. Role of uncondensed 1,2,4-triazine derivatives as biocidal plant protection agents. A review part XV. Phamazie, 2001, 56(3), 195-204.
[11]
Abdel-Rahman, R.M.; Abdel-Malik, M.S. Synthesis of some new 3,6-diheteroaryl-1,2,4-triazin-5-ones and their effect on amylolytic activity of some fungi. Pak. J. Sci. Ind. Res., 1990, 33(4), 142-147.
[12]
Blakley, B.; Brousseau, P.; Fournier, M.; Voccia, I. Immunotoxicity of pesticides: A review. Toxicol. Ind. Health, 1999, 15, 119-132.
[13]
Schmidt, R.R.; Draber, W.; Eue, L.; Timmler, H. Herbicidal activity and selectivity of new 3-alkyl-4-amino-6-aryl-1,2,4-triazin-5-ones. Pest. Sci., 1975, 6(3), 239-244.
[14]
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, 154-168.
[15]
Abdel-Rahman, R.M.; Saad, H.A. Synthesis and chemical behavior of 1,2,4-triazine derivatives bearing phosphorus amides as donor-acceptor: A review. Curr. Org. Synth., 2016, 13(3), 408-425.
[16]
Gergely, J.; Morgan, J.B.; Overman, L.E. Stereocontrolled synthesis of functionalized cis-cyclopentapyrazolidines by 1,3-dipolar cycloaddition reactions of azomethine imines. J. Org. Chem., 2006, 71(24), 9144-9152.
[17]
Bolm, C.; Kasyan, A.; Saladin, S. Synthesis of novel silylated 1,2,4-triazin-5-ones. Tetrahedron Lett., 2005, 46(23), 4049-4051.
[18]
Liu, S.J.; Cui, L.B.; Xu, H.; Wang, T.Y.; Hu, C.; Li, S.; Lin, H.Q.; Wan, D.C. Design, synthesis, and biological evaluation of 7H-thiazolo[3,2-b]-1,2,4-traizin-7-one derivatives as dual binding site acetylcholinesterase inhibitors. Heterocycles, 2013, 87(12), 2607-2614.
[19]
Holla, B.S.; Malini, K.V.; Sarojini, B.K.; Poojary, B. A novel three-component synthesis of triazinothiazolones. Synth. Commun., 2005, 35(3), 333-340.
[20]
Heravi, M.M.; Nami, N.; Oskooie, H.A.; Hekmatshoar, R. One-pot synthesis of some nitrogen and sulfur heterocycles using thiosemicarbazide under microwave irradiation in the solventless system. Phosphorus Sulfur Silicon Relat., 2006, 181(1), 87-91.
[21]
Kögler, M.; Busson, R.; De Jonghe, S.; Rozenski, J.; Van Belle, K.; Louat, T.; Munier-Lehmann, H.; Herdewijn, P. Synthesis and evaluation of 6-aza-2′-deoxyuridine monophosphate analogs as inhibitors of thymidylate synthases, and as substrates or inhibitors of thymidine monophosphate kinase in Mycobacterium tuberculosis. Chem. Biodivers., 2012, 9, 536-556.
[22]
Abdel-Rahman, R.M.; Seada, M.; Fawzy, M.; El-baz, I. Synthesis of some new 1,6-dihydro-3-substituted 6-spiro(9ʹ-fluorene)-1,2,4-triazin-5-(4H)ones as potential anti-HIV and anticancer drugs. Pharmazie, 1994, 49(10), 729-733.
[23]
Bakhotmah, D.A. Synthesis of novel α-amino acids bearing 1,2,4-triazinone and steroidal moieties as enzymatic affect (cellobiase activity) part I. Inter. J. Chem., 2015, 7(1), 98-103.
[24]
Ghassemzadeh, M.; Heravi, M.M.; Neumuller, B. Synthesis, characterization and crystal structures of new palladium(II) complexes and the first platinum(III) complex containing ATT (ATT = 6-aza-2-thiothymine). Z. Anorg. Allg. Chem., 2005, 631(12), 2401-2407.
[25]
Ibrahim, Y.A.; Al-Saleh, B.; Mahmoud, A.A. Intramolecular 4+2 cycloaddition of thieno[2,3-e][1,2,4]triazines: Routes towards condensed thieno[2,3-b]pyridines. Tetrahedron, 2003, 59(43), 8489-8498.
[26]
Abdel-Rahman, R.M.; Seada, M.; Fawzy, M.; Baz, I. Synthesis of some new heterobicyclic compounds containing spiro-1,2,4-triazine moiety as potential anti-HIV and anticancer agents. Pharmazie, 1994, 49(11), 811-814.
[27]
Sasaki, T.; Iot, E. Synthesis of bridgeheaded nitrogen systems. s-triazolo[4,3-b]-as-triazine, s-triazolo[4,3-d]-as-triazine and s-tria-zolo[3,4-b]-l,3,4-thiadiazole ring systems. J. Heterocycl. Chem., 1981, 18(7), 1353-1356.
[28]
Al-Awadi, N.A.; Ibrahim, Y.A.; Dib, H.H.; Ibrahim, M.R.; George, B.J.; Abdullah, M.R. Comparative studies for selective deprotection of the N-arylideneamino moiety from heterocyclic amides: kinetic and theoretical studies. Part 2. Tetrahedron, 2006, 62(26), 6214-6221.
[29]
Abdel-Rahman, R.M.; Makki, M.S.T.; Ali, T.E.; Ibrahim, M.A. 1,2,4-Triazine chemistry part I: Orientation of cyclization reactions of functionalized 1,2,4-triazine derivatives. Eur. J. Chem., 2010, 1(3), 236-245.
[30]
Abdel-Rahman, R.M.; El-Gendy, R.M.; Abdel-Halim, A.M. Synthesis and biological activity of 1,2,4-triazinotriazinone derivatives. Pharmazie, 1995, 50(11), 726-729.
[31]
Hakimi, F.; Tabatabaee, M.; Heravi, M.; Roshani, M.; Bamoharam, F. Heteropoly acid catalyzed selective cyclization of 6-alkyl-3- propargylmercapto-1,2,4-triazin-5(2H)-one. E-J. Chem., 2011, 8(2), 798-802.
[32]
Mansour, A.K.; Eid, M.M.; Khalil, N.S. Selective synthesis and reactions of 6-substituted-2-β-galactosyl-1,2,4-triazines of potential anticancer activity. Nucleos. Nucleot. Nucleic Acids, 2003, 22(1), 21-44.
[33]
Khalil, A.A.; Hamide, S.G.A.; Al-Obaid, A.M.; El-Subbagh, H.I. Substituted quinazolines, Part 2. Synthesis and in-vitro anticancer evaluation of new 2-substituted mercapto-3H-quinazoline analogs. Archiv. Der. Pharm., 2003, 336(2), 95-103.
[34]
Ashour, H.M.; El-Wakil, M.H.; Khalil, M.A.; Ismail, K.A.; Labouta, I.M. Synthesis of some (E)-6-[2-(furan-2-yl)ethenyl]-1,2,4-triazin-5-ones and their biological evaluation as antitumor agents. Med. Chem. Res., 2013, 22(4), 1909-1924.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 4
Year: 2019
Published on: 19 March, 2019
Page: [308 - 322]
Pages: 15
DOI: 10.2174/1570193X15666180807124325
Price: $65

Article Metrics

PDF: 67
HTML: 5
EPUB: 1
PRC: 2