1, 2, 4-TRIAZOLES: AS BIOLOGICALLY IMPORTANT AGENTS

1, 2, 4-TRIAZOLES: AS BIOLOGICALLY IMPORTANT AGENTS

D. Kumudha*¹, R. R. Reddy ¹ and T. Kalavathi ²

Arya College of Pharmacy ¹, Kandi, Sangareddy, Medak- 85, Andra Pradesh, India

Nirmala College of Pharmacy ², Kadapa, Andra Pradesh, India

ABSTRACT

The chemistry of heterocyclic compounds containing five membered 1, 2, 4-triazole nucleus has been an intresting field of study for past few decades. The five membered 1, 2, 4-triazole ring exists in two tautomeric forms i.e., 1H-1, 2, 4-triazole, 4H-1, 2, 4-triazole collectively known as s-triazoles. The s-triazole derivatives possess extensive spectrum of biological activities such as antibacterial, antifungal, antitubercular, anxiolytic, anticonvulsant, anti-inflammatory, analgesic, anticancer, antioxidant activities. The present review provides a broad view of pharmacological activity of compounds bearing 1, 2, 4-triazole nucleus. It can be useful for medicinal chemists to design and develop novel compounds consisting   1, 2, 4-triazole nucleus to get better agents in terms of efficacy and safety.

1, 2, 4-triazole derivatives, Antimicrobial, Anticonvulsant, Anticancer Activities

INTRODUCTION: The 1, 2, 4-triazole is a five membered heterocyclic compound containing two carbons and three nitrogens with a molecular formula of C₂H₃N₃. It exists in two tautomeric forms. 1H and 4H-1, 2, 4-triazole is considered to be pharmacologically important nucleus.

The literature review shows that 1, 2, 4-triazole possess wide spectrum of biological activities. In particular compounds having 1, 2, 4-triazole nucleus are known to have excellent antibacterial, antifungal, antitubercular, antioxidant, anticancer, anti-inflammatory, analgesic, anticonvulsant, anxiolytic  activities ¹.

Biological Activities of 1, 2, 4-Triazoles:

As Antibacterial and Antifungal agents: Xin-Ping Hui et al, prepared variety of 5-(5-methylisoxazol-3-yl)-1,3,4-thiadiazoles, 1,2,4-triazoles and 1,3,4-oxadiazoles and evaluated for their antibacterial potency ².

3. Shivarama Holla et al, prepared variety of diaryloxy-methyl-substituted-1,2,4-triazolo [3,4-b]-1,3,4-thiadi-azoles and evaluated for antibacterial activity ³.
4. Shivarama Holla et al, prepared a series of 6-(5-aryl-2-furyl)-1,2,4-triazolo [3,4-b]-1,3,4-thiadiazoles and investigated for antibacterial potency ⁴.
5. Shivarama Holla et al, reported the synthesis of N-bridged heterocycles such as triazolothiadiazoles, bis-triazolothiadiazoles, triazolothiadiazines, triazolothiadi-azinones derived from 3-aryloxymethyl-4-amino-5-mercapto-1,2,4-triazoles and evaluated for their antibacterial activity ⁵.
6. Shivarama Holla et al, reported the synthesis of various bis–(4-amino-5-mercapto-triazol-3-yl)alkanes, their schiffs bases and bis-(1,2,4-triazolo[3,4-b]-1,3,4-thiadiazol-4-yl]alkanes and investigated as potent antibacterial agents⁶.
7. Mogilaiah et al, prepared a series of 1-arylazetidino [2,3-b][1,8]napthyridin2-(1H)-ones and 1-aryl-4-carbethoxy-1,2,4-triazolo[4,3-a][1,8] naphthyridines and tested for antibacterial potency⁷.
8. S. Sudha et al, reported the synthesis of 5-[(4-aroyl) aryloxymethyl]-2-(4-methylphenylamino)-1,3,4-thiadiazoles and 5-[(4-aroyl)aryloxymethyl]-4-(4-methyl)-3-mercapto-4H-1,2,4-triazoles and investigated as antibacterial agents⁸.
9. K. Ravi et al, reported the synthesis of 1,2,4-triazoles derivatives of anthranalic acid and for their antibacterial activity ⁹.
10. V. Mulwad et al, had reported the synthesis of a series of oxadiazolo(1,3,5)-triazines, 1,2,4-triazoles and thiadiazolo 1,3,4-oxadiazole analogues and investigated for their antibacterial activity ¹⁰.

Umesh Kumar et al, reported the synthesis of 4-amino-5-aryl-1,2,4-triazoles and screened for their antibacterial activity ¹¹.

Nizamuddin et al, reported the synthesis of 2-Aryl/aryloxy methyl-1,3,4-oxa/thiadiazolo[4,5-b]1,2,4-triazolo[5,4-c]thiazolo-spiro-7-cyclohexanes and investigated as fungicidal agents ¹².

Anees A Siddiqui et al, reported the synthesis of a series of 3-(p-substituted anilinoethyl)-4-(p-substituted phenyl)-5-thioxo-1,2,4-triazoles and investigated as active antifungal agents ¹³.

Qing-Yan Sun et al, prepared various 1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substitutedphenyl)-piperazin-1-yl)-propan-2-ols and investigated for their antifungal potency ¹⁴.

Yong Sun et al, synthesized 2-alkylamino-3-aryl-6-(1H)-1,2,4-triazol-1-yl)-thieno (2,3-d)-pyrimidin-4(3H)-ones and evaluated for fungicidal activity. Compound 6h showed excellent activity ¹⁵.

Jag Mohan et al, synthesized s-triazolo[3,4 b)[1,3,4] thiadizoles, s-triazolo(3,4 – b)[1,3,4]thiadiazines and s-triazolo(3’,4’-2,3)[1,3,4-thiadizino[5,6-b]quinoxalines and evaluated for antimicrobial potency ¹⁶.

Jagmohan et al, prepared s-triazolo[3,4-b][1,3,4] thiadiazoles and s-triazolo[3,4-b][1,3,4]thiadiazines and evaluated for antifungal and antibacterial activities ¹⁷.

18. M. Hirpara et al, synthesized a series of 6-aryl-3-pyridin-4-yl-5,6-dihydro[1,2,4]-triazolo[3,4-b][1,3,4]-thiadiazoles and investigated for antimicrobial activity ¹⁸.
19. M. Srinivasa et al, reported the synthesis of 8-fluoro-9-substituted(1,3)-benzothiazolo(5,1-b)-3-substituted triazoles and investigated for their antimicrobial activities ¹⁹.

Arun Kumar Wahi et al, prepared N-(substituted benzylidene)-2-(N-(4H-1,2,4-triazole-4-yl)benzamido) acetohydrazides and N-((5-substitutedaryl)-1,3,4-oxadiazole-2-yl)methyl-N-(4H-1,2,4-triazole-4-yl)benzamides  and screened for antibacterial and antifungal activity ²⁰.

Mudasir Rashid Banday et al, reported the synthesis of substituted triazoles and thiazolidinones from fatty acids and screened for antimicrobial activity ²¹.

22. A. Baviskar et al, synthesized thiazolyltriazole substituted azetidinone derivatives and evaluated for their antimicrobial activity²².

Bahittin Kahveci et al, reported the synthesis of 3-alkyl-4-(arylmethyleneamino) 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives and screened for the antimicrobial activity²³.

24. Shivakumar et al, synthesized 3-aryl-oxymethyl-4-[2-(benzimidazolyl thio)acetamide]-5-mercapto-1,2,4-triazoles and evaluated for their antimicrobial activities ²⁴.

Jag Mohan prepared a series of s-triazolo(3,4-b)(1,3,4)thiadiazoles, s-triazolo (3,4-b)(1,3,4) thiadiazines and screened for their antibacterial and antifungal activities ²⁵.

Chang –Hu Chu et al, prepared a series of ω-(5-arylamino-1,3,4-thiadiazol-2-thiol)-ω-(1H-1, 2, 4-triazol-yl)acetophenones and screened for antifungal and growth regulatory activities ²⁶.

Balakrishna Kalluraya et al,  prepared 3-alkyl-/aryl-9-substituted 1,2,4-triazolo[3,4-b][1,3,4]quinolino thiadiazipines and selected compounds were screened for their antibacterial and antifungal activities ²⁷.

Nasser S. A. M. Kalil synthesized N-and S-α-L-arabinopyranosyl[1,2,4]triazolo[3,4-b][1,3,4]thiadi- azoles and investigated for antimicrobial potency ²⁸.

29. K. Swamy et al, synthesized 3-substituted(1,2,4)-triazolo[3,4-b]1,2-benzisoxazole derivatives and tested for their antimicrobial activity ²⁹.

A.M. Manikaro et al, reported the synthesis of substituted 4-(N-pyridyl-5-4-amino-s-triazole-5-thiolate and evaluated for antimicrobial activity ³⁰.

Harish Rajak et al, prepared 4-substituted piperizin-1yl)phenyl]-4-substituted 2,4-dihydro[1,2,4] triazole-3-thiones and evaluated for antimicrobial activity ³¹.

Rajkumar Agarwal et al, synthesized 5- aromatic substituted -4H-1,2,4-triazol-3-thiol and evaluated for antimicrobial activity ³².

Mrs. Arti Singh et al, reported the synthesis of N-(disubstituted amino)methyl(4H)-1,2,4-triazole-4-yl)benzamide and investigated for antimicrobial activity ³³.

As diuretic agents: Jag Mohan reported the synthesis of 3-(2-thienyl)-s-triazolo[3,4-b][1,3,4]-thiadiazole, 2-(2-thienyl)thiazolo[3,2-b]-s-triazole and isomeric 3-(2-thienyl)-thiazolo(2,3-c)-s-triazole and screened for their diuretic, antibacterial and antifungal activities ³⁴.

As anti-inflammatoty agents: Arun K. Wahi et al, synthesized the series of N-substituted benzylidene)-2-N-(4H-1,2,4-triazole-4yl)benzamido acetohydrazides and evaluated for antimicrobial and anti-inflammatory activities ³⁵.

Rajive Gupta et al, synthesized a series of 3-alkyl/aryl-6-(2-chloro-2-            substituted-phenylethenyl)-5-b-dihydro-s-trizolo[3,4-b][1,3,4].thiadiazoles and evaluated for anti-inflammatory, antibacterial and antifungal activities ³⁶.

Rohini Diwedi et al, synthesized several 5,5’-Methylene bis(4-substituted phenyl/alkyl)-4H-1,2,4-triazole-3-thiol and  investigated for their antioxidant, anti-inflammatory activities³⁷.

Mario Di Braccio et al, prepared 5-(alkylamino)-N-N-diethyl[1,2,4]triazolo[4,3-a][1,8]napthyridine carboxamide and its derivatives and screened for their anti-inflammatory activity ³⁸.

Ram Janam Singh et al, synthesized 1,2,4-triazolothiadiazines, 1,2,4-triazolothiadiazinones and evaluated for anti-inflammatory activity ³⁹.

As anticancer agents: S. B. Hipara et al, reported the synthesis of 2-aryl 5-(2’-methoxy-5’-methylphenylamino)-1,3,4-thiadiazoles and 2-Phenyl-4-arylidine-1-(2’-methoxy-5’-methylphenyl thiourido-5-oxo-imidazolines and investigated for their antibacterial, antifungal and anticancer activities⁴⁰.

Olcay Bekircan et al, reported the synthesis of various 4-arylidenamino-4H-1,2,4-triazoles, 4-(1-aryl)ethylidenamino-4H-1,2,4-triazoles, 4-arylmethyl amino-4H-1,2,4-triazoles, 4-(1-aryl)ethylamino-4H-1,2,4-triazoles and investigated as weak anticancer agents ⁴¹.

Zhi Zhang Li et al, were prepared various 4-(arylmethyl benzylidene amino)-5-phenyl-2H-1,2,4-triazole-3-(3H)-thiones and N-2,3,4,6-tetra-O-acetyl-acetyl-σ-D-glucopyranosyl-4-(arylmethylideneamino)-5-phenyl-2H-1,2,4-triazole-3(4H)-thione and investigated for their antiproliferative agents ⁴².

Elzbieto Pomarnacka et al, synthesized 2-arylamino-8-chloro-5,5-dioxo[1,2,4]-triazolo[2,3-b][1,4,2]benzodithi -azines and investigated for their anticancer and antibacterial activities ⁴³.

Wageesh S.El Hamouly et al, reported the synthesis of N-substituted sulphonyl, 1,2,4-triazole, N-substituted benzylidene and pyrazole analogues bearing 4-(benzo(d)thiazol-2-yl)benzohydrazide and evaluated for antibreast cancer activity ⁴⁴.

Hend A. A. Abd El-Wahab et al, synthesized substituted 1,2,4- triazole-3-acetic acid derivatives and evaluated  for antitumor and anti-inflammatory activities ⁴⁵.

Ibrahim F. Nasser et al, were synthesized 2- alkylthio-7-tosyl-7H-pyrazolo (4,3-e)[1,2,4-]-triazolo[1,5-c] pyrimidines and other pyrazole derivatives and evaluated for their antitumour activity ⁴⁶.

As antitubercular agents: Shashikant Patten et al, reported the synthesis of 5-mercapto 1,2,4-triazole derivatives and evaluated for antimicrobial, anti-inflammatory, antitubercular activities ⁴⁷.

Mahendra Ramesh Shiradkar et al, reported the synthesis of various derivatives of N-{4-[(4-amino-5-sulphanyl-4H-1,2,4-triazol-3-yl)methyl]-1,3-thiazol-2-yl}-2-substituted amides and tested for antibacterial and antitubercular potency ⁴⁸.

Mahendra Shiradkar et al, synthesized analogues of thiazolyl triazoles and tested for their antimycobacterial and antimicrobial activities ⁴⁹.

As anticonvulsant agents: Hong Guang Jin et al., reported the synthesis of 7-alkoxy-4,5-dihydro[1,2,4]triazolo[4,3-a]quinoline1(2H)-ones and investigated for anticonvulsant activity and neurotoxicity ⁵⁰.

51. Moreau et al., reported the synthesis of 3-amino-7-(2,6-dichlorobenzyl)-6-methyltriazolo[4,3-b]pyridine derivatives of amide and carboxylic acid and investigated for their anticonvulsant potency⁵¹.

Zhi-Feng Xie et al, prepared various 7-alkoxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline analogues and were investigated for their anticonvulsant activity and neurotoxicity. Compound(4l) is found to be very active ⁵².

Dayanand  Kadadevar et al., reported the synthesis and evaluation of N-(substitutedphenyl)-2-[5-phenyl-2H-1,2,4-triazol-3-yl-amino]acetamide for their anticonvulsant activity ⁵³.

As Anxiolytic agents: Anil M. Manikaro et al, synthesized carboxamidoethylthio-(4H)-1,2,4-triazoles and evaluated for anxiolytic, anti-inflammatory, analgesic activity ⁵⁴.

As Antioxidant agents: M. Suresh et al, reported the synthesis of 8-chloro-1,4-substituted (1,2,4[4,3-a]quinoxalines and evaluated for antioxidant and antimicrobial activity ⁵⁵.

As Human V1A receptor antagonists: Akio Kakefuda et al, synthesized 5-(4-biphenyl)-3-methyl-4-phenyl-1,2,4-triazole derivatives and investigated as selective antagonists for the human vasopression V1A receptor ⁵⁶.

As PPARα agonists: Yan Ping Xu et al., reported the design and synthesis of various 2, 4-dihydro-3H-1, 2, 4-triazol-3-one, and investigated as most potent and selective PPARα agonist ⁵⁷.

As Analgesic agents: P. K. Goyal et al., were synthesized s-substituted -4-(3-disubtituted-1-triazenyl)-4H-1,2,4-triazol-5-thiol and tested for analgesic activity ⁵⁸.

CONCLUSION: The present study revealed that  1,2,4-triazole derivatives are the significant class of heterocyclic compounds and showed promising pharmacological activities like antibacterial, antifungal, antitubercular, antioxidant, anticancer, anti-inflammatory, analgesic, anticonvulsant, anxiolytic, activities. These observations have been useful for the development of 1, 2, 4-triazole nucleus which can be taken as a lead for future development to get safer and effective compounds.

REFERENCES

1. A.K. Wahi, Arti Singh. Triazole: Recent development and biological activities. Asian Journal of Biochemical and Pharmaceutical Research 2011; 1(2): 193-205.
2. Xin-Ping Hui, Lin-Mei Zhang and Zi-Yi Zhang. Synthesis and antibacterial activities of 1,3,4-thiadiazole, 1,3,4-oxadiazole and 1,2,4-triazole derivatives of 5-methylisoxazole. Ind. J. Chem 1999; 38B: 1066-1069.
3. B. Shivarama Holla, Alphonsus D’ Souza and Balakrishna Kalluraya. Synthesis of some 2,5-diaryloxymethyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles. Ind. J. Chem. Soc 1991; 68: 250-251.
4. B. Shivarama Holla and P. Mohammed Akberali. Studies on Arylfuran heterocycles: Part-1. Synthesis of 6-(5-Aryl-2-furyl)-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles. Ind. J. Chem. Soc 1991; 68: 341-343.
5. B. Shivarama Holla, K. Shridhara and M. K. Shivanada. Synthesis and antibacterial activity of N-bridgedheterocycles derived from aryloxymethylthiazoles. Ind. J. Chem 2002; 41B: 1257-1262.
6. B. Shivarama Holla, B. Veerendra, M. K. Shivananda and N. Sucheta Kumari. Synthesis and biological activity of some bis-triazole derivatives. Ind. J. Chem 2003; 42B: 2010-2014.
7. K. Mogilaiah, P. Raghotham Reddy, R. Babu Rao and N. Vasudeva Reddy. Synthesis of some novel azetidino[2,3-b][1,8]naphthyridin-2(1H)-ones and 1,2,4-triazolo[4,3-a][1,8]naphthyridines. Ind. J. Chem 2003; 42B: 1746-1749.
8. B. S. Sudha, S. Shashikanth and Shaukanth Ara Khanum. Synthesis and antimicrobial activity of 5-[(4-aroyl) aryloxy]-2-4-methylamino)1,3,4-thiadiazoles and 5-[(4-aroyl) aryloxy methyl]-4-(4-methylphenyl)-3-mercapto-4H-1,2,4-triazoles. Ind. J. Chem 2003; 42B: 2652-2656.
9. T. K. Ravi and Rajkannan. Synthesis and antimicrobial activity of some new 1,2,4-triazoles. Ind. J. Pharm. Sci 2004; May-June: 347-350.
10. V. V. Mulwad, Atul C.Chaskar. Synthesis and antibacterial activity of new oxadiazolo[1,3,5]-triazine, 1,2,4-triazolo and thiadiazolo 1,3,4-oxadiazole derivatives. Ind. J. Chem 2006; 45B: 1710-1715.
11. Umesh Kumar, M. Bansal, Shiv K. Gupta, M. Saha Ryar. Synthesis of 4-amino-5-aryl-1,2,4-triazoles and screening for antibacterial activity. Int. J. Chem. Sci 2008; 6(1): 262 -268.
12. Nizamuddin, Shafqat Alauddin, H. C. Gupta and Manoj Kumar Srivatava. Synthesis and biocidal activity of 2-aryl/aryloxymethyl-1,3,4-oxa/thiadiazolo[4,5-b][1,2,4]triazolo[5,4-c]thiazolo-spiro-7-cyclohexanes. Ind. J. Chem 2002; 41B: 1314-1318.
13. Anees A. Siddiqui, Amit Arora, N. Siddiqui and Amit Misra. Synthesis of some 1,2,4-triazoles as potential antifungal agents. Ind. J. Chem 2005; 44B: 838-849.
14. Qing-Yan Sun, Wan-Nian Zhang, Jian-Ming Xu, Yong-Bing Cao, Qiu-Ye Wu, Da-Zhi Zhang et al. Synthesis and evaluation of novel 1-(1H- 1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substitutedphenyl)-piperazin-1-yl]-propan-2-ols as antifungal agents. Eur. J. Med. Chem  2007; 42: 1151-1157.
15. Yong Sun, Jing Wu Ling Feng and Ming-Wu Ding. Efficient synthesis and fungicidal activities of 2-alkylamino-3-aryl-6-(1H-1,2,4-triazol-1-yl)-thieno[2,3-d]pyrimidin-4(3H)-ones. ARKIVOC 2009; (vii): 111-118.
16. Jag Mohan, G. S. R. Anjaneyulu and K. V. S. Yamin. Heterocyclic systems containing bridgehead nitrogen atom: Synthesis and antimicrobial activity of s-triazolo[3,4-b][1,3,4]thiadiazoles, s-triazolo[3,4-b][1,3,4]thiadiazines, s-triazolo [3’,4’:2,3][1,3,4] thiadiazino[5,6-b]quinoxaline. J. Ind. Chem. Soc 1991; 68: 474-476.
17. Jagmohan and Ashok Kumar. Condensed bridgehead nitrogen heterocyclic systems: Synthesis and antimicrobial activity of s-triazolo[3,4-b][1,3,4]thiadiazoles and s-triazolo[3,4-b][1,3,4]thiadiazines. Ind. J.  Heterocycl. Chem 2001; 11: 71-74.
18. H. M. Hirpara, V. A. Sudha, A. M. Trivedi, B. L. Khatri and A. R. Parikh. Microwave assisted synthesis and biological activities of some bridgehead nitrogen heterocycles. Ind. J. Chem 2003; 42B: 1756-1759.
19. G. M. Srinivasa, E. Jayachandran and B. Shivakumar. Synthesis of 8-fluoro-9-substituted (1,3)benzothiazolo(5,1-b)-3-substituted 1,2,4-triazoles. Ind. J. Heterocycl. Chem 2004; 14: 89-90.
20. Arun Kumar Wahi, Arti Singh and Ajit Kumar Singh. Determination of minimum inhibitory concentration of some novel triazole derivative. IJRPC 2011; 1(4): 1108-1114.
21. Mudasir Rashid Banday and Abdul Rauf. Substituted 1,2,4-triazoles and thiazolidinones from fatty acids: Spectral characterization and antimicrobial activity.  Ind. J. Chem  2009; 48B: 97-102.
22. B. A. Baviskar, M. R. Shiradkar, S. S. Khadabadi, S. L. Deore, K. G.  Bothara, Synthesis of thiazolyltriazole substituted azetidinones as antimicrobial agents. Ind. J. Chem 2011; 50B: 321-325.
23. Bahittin Kahveci, Olcay, Bekircan, Sengul, Alpay Karaoglu. Synthesis and antimicrobial activity of some 3-alkyl-4-(arylmethyleneamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones. Ind. J. Chem 2005; 44B: 2614-2617.
24. R. Shivakumar, Shobharam Sahu, T. Y. Pasha, R. H. Udupi, A. R. Bhat, R. Nagendra Rao, Veerana Goud. Synthesis and biological evaluation of 3-aryloxy methyl-4-[-2’(benzimidolyl thio acetamide]-5-mercapto-1,2,4-triazoles. Int. J. Chem. Sci 2008; 6(1): 405-412.
25. Jag Mohan. Bridgehead nitrogen heterocyclic system: Facile synthesis and bioactivityof s-triazolo[3,4-b][1,3,4]thiadiazoles, s-triazolo[3,4-b][1,3,4]thiadiazines and related heterocycles. Ind. J. Chem 2005; 44B: 628-630.
26. Chang-Hu-Chu, Xin.Ping Hui, Peng-Fei Xu, Zi-Yi Zhang, Zhi- Chun Li and Ren –An Liao. Synthesis and antifungal activities of ω-(5-arylamino-1,3,4-thiadiazol-2-thio) –ω-(1H-1,2,4-triazol-1-yl)acetophenones. Ind. J. Chem 2002; 41B: 2436-2438.
27. Balakrishna Kalluraya, R. Gururaja, Ganesha Rai, One pot reaction: Synthesis, characterization and biological activity of 3-alkyl/aryl-9-substituted 1,2,4-triazolo[3,4-b][1,3,4]quinolino thiadiazepines. Ind. J. Chem 2003; 42B: 211-214.
28. Nasser S. A. M.Kalil. N and S –α-L-Arabinopyranosyl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles.First synthesis and evaluation. Eur. J. Med. Chem 2007; 42: 1193-1199.
29. D. K. Swamy and M. V. Desh Much. Novel approach to the synthesis of 3-substituted (1,2,4)triazolo(3,4-b)1,2-benzisoxazole and their antimicrobial activity. J. Chem. Pharm. Res 2010; 2(3): 699-703.
30. A. M. Manikaro, Pravin N-Khatale, T. Sivakumar, D. R. Chaple, Drafulla M. Sable, Rahul D. Jawarkar. Characterization, evaluation of products synthesized in the interaction of 4-(N-substituted)-3-pyridyl- 5- mercapto-S-triazole with secondary amines. Der  Pharma Chemica 2011; 3(5): 334-340.
31. Harish. Rajak, Bhupendra S. Thakur, Poonam Pamar, Pramod Kumar Gupta, Navneeth Agarwal and Prabodth Chander Charma. Antimicrobial activity of some novel triazole-3-thione containing substituted piperazine moiety. Der Pharma Chemica 2011; 3(3): 422-426.
32. Rajkumar Agarwal and S. S. Pancholi. Synthesis, characterization and evaluation of antimicrobial activity of a series of 1,2,4-triazoles. Der Pharma Chemica 2011; 3(6): 32-40.
33. Arti Singh and A. K. Wahi. Synthesis, Characterization and Antimicrobial activity of some new Mannich bases derived from 4-amino triazoles. RJPBCS 2011; 2(2): 896-903.
34. Jag Mohan. Heterocyclic systems containing bridgehead nitrogen atom: Synthesis and bioactivity of 3-(2-thienyl)-s-triazolo[3,4-b][1,3,4]thiadiazole, 2(2-thienyl) thiazolo[3,2-b]-s-triazole and isomeric 3-(2-thienyl)thiazolo[2,3-c]-s-triazole. Ind. J. Chem 2003; 42B: 401-404.
35. Arun K. Wahi, Ajit K. Sing and Arti Singh. Design and synthesis of novel schiff’s bases having N-(4H-1, 2, 4-triazole-4-yl)benzamido moiety as antimicrobial and anti-inflammatory agents. Der Pharma Chemica  2011; 3(5): 146-154.
36. Rajive Gupta, Satya Paul, Avinash K. Gupta. Heterocyclic systems containing bridgehead nitrogen atom: Synthesis and biological activities of some substituted s-triazolo[3,4-b][1,3,4]thiadiazoles. Ind. J. Chem 1998; 37B: 498-501.
37. Rohini Diwedi, S.Alexander, M. J. N. Chandrasekar. Rapid and efficient synthesis of microwave assisted some bis-1,2,4-triazole derivatives and their antioxidant and anti-inflammatory evaluation. RJPBCS 2011; 2(1): 194-204.
38. Mario Di Braccio, Giancarlo Grossi, Giorgio Roma, Daniela Piras, Francesca, Mattioli, Marzia Gosmar.1,8-Naphthyridines VI. Synthesis and anti-inflammatory activity of 5-(alkylamino)-N, N- diethyl[1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxamides with a new substitution pattern on the triazole ring. Eur. J. Med. Chem 2008; 43: 584-594.
39. Ram Janam Singh, Dharmendra Kumar Singh. Novel synthetic approach to some new 1, 2, 4-Triazolothiadiazines and 1, 2, 4-Triazolothiadiazinones and their anti-inflammatory activities. Int. J. Chem. Tech. Res 2009; 1(4): 1239-1243.
40. S. B. Hipara, K. A. Parikh, B. C. Merja and H. H. Parekh. 2-Methoxy-5-methylphenyl thiosemi carbazide: A versatile molecule for the synthesis of thiadiazoles and imidazolinones possessing multiple biological activities. Ind. J. Chem 2003; 42B: 1172-1175.
41. Olcay Bekircan and Nurhan Gumrukcuoglu. Synthesis of some 3,5-diphenyl-4H-1,2,4-triazole derivatives as antitumor agents.  Ind. J. Chem 2005; 44B: 2107-2113.
42. Zhi Zhang Li, Zheng Gu, Kai Yin, Rong Zhang, Qin Deng, Jiannan Xiang. Synthesis of substituted phenyl-1,2,4-triazol-3-thione analogues with modified D-glucopyranosyl residues and their antiproliferative activities. Eur. J. Med. Chem 2009; 44: 4716-4720.
43. Elzbieto Pomarnacka, Patrick. J. Bednarski, Przemyslaw Reszka, Ewa Dziemidowiez-Borys, Andrzej Bienezak, Wladyslaw Werd, et al. Synthesis and biological activity of new 2-amino-8-chloro-5,5-dioxo[1,2,4]triazolo[2,3-b][1,4,2]benzodithiazines. Eur. J. Med. Chem 2006; 41: 633-639.
44. Wageeh S. El Hamouly ,Kamelia M. Amin, Samy A.El Assaly and Eman A. Abd El Meguid. Synthesis and antitumor activity of some new N-substituted-sulfonyl, 1, 2, 4-triazole, N-substituted-benzylidene and pyrrole derivatives attached to 4-(benzo[d] thiazol-2-yl)benzohydrazide. Der Pharma Chemica 2011; 3(6): 293-306.
45. Hend A. A. Abd El-Wahab, Hamdy, M. Abdel Rahman, Gamal-Eldin S. Alkaramany and Mahmoud A. El. Gendy. Synthesis, biological evaluation and molecular modeling study of substituted 1,2,4-triazole-3-acetic acid derivatives.  Der Pharma Chemica 2001; 3(6): 540-552.
46. Ibraham F. Nassar and Samy A. El. Assaly. Synthesis, reactivity and antitumor activity of some new pyrazolo[3,4-d] pyrimidine and their triazole derivatives. Der Pharma Chemica 2011; 3(1): 229-238.
47. Shashikant Pattan, Priyanka Gadhave, Vishal Tambe, Santhosh Dengale, Deepak Thakur et al. Synthesis and evaluation of some novel 1,2,4-triazole derivatives for antimicrobial, anti-tubercular, anti-inflammatory activities. Ind. J. Chem 2012; 51B: 297-301.
48. Mahendra Ramesh Shiradkar, Kiran Kumar Murahari, Hanimi Reddy Gangadaru, Tatikonda Suresh, Chakravarthy, Akula Kalyan, et al. Synthesis of new S-derivatives of clubbed triazolyl thiazole as anti-Mycobacterium tuberculosis agents. Bioorg. Med. Chem 2007; 15: 3997-4008.
49. Mahendra Shiradkar, Gorentla Venkata Suresh Kumar, Varaprasad Dasari, Suresh Tatikonda, Kalyan Chakravarthy Akula, Rachit Shah. Clubbed triazoles: A novel approach to antitubercular drugs. Eur. J. Med Chem 2007; 42: 807-816.
50. Hong-Guang Jin, Xian Yu Sun, Kyu-Yun Chai, Hu Ri Piao and Zhe-Shen Quan. Anticonvulsant and toxicity evaluation of some 7-alkoxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline-1(2H)-ones. Bioorg. Med. Chem 2006; (14): 6868-6873.
51. S. Moreau, Pascal Coudest, Catherine Rubat, Danielle Vallee-Goyet,  Gardette, Jean-Claude Gramain et al. Synthesis and anticonvulsant properties of triazolo- and imidazopyridazinyl carboxamides and carboxylic acids. Bioorg. Med. Chem 1998; 6: 983-991.
52. Zhi-Feng Xie, Kyu-Yunchai, Hu Ri Piao, Kyung Chell Kwak and Zhe Shan Quan. Synthesis and anticonvulsant activity of 7-alkoxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolines. Bioorg. Med. Chem. Lett 2005; (15): 4803-4805.
53. Dayanand  Kadadevar, Chalivaraju K. C, Niranjan M. S, Chandrasekar Sulthanpur, Santosh Kumar Madinur, Nagaraj, et al. Synthesis of N-(Substituted Phenyl)-2-[5-Phenyl-2H-1, 2, 4-triazol-3ylamino]Acetamide as Anticonvulsant. Int. J. Chem. Tech. Res  2011; 3(3): 1064-1069.
54.  Anil M. Manikrao, Ravindra A. Fusule, K. S. Rajesh, Harish K. Kunjwani and Prafulla M.Sabale. Synthesis and biological screening of novel derivatives of  3-(N-substituted  carboxamodo ethylthio)-4H-1,2,4-triazoles.Ind. J. Chem 2010; 49B: 1642-1647.
55. M. Suresh, P. Lavanya, D. Sudhakar, K. Vasu and C. Venkata Rao. Synthesis and biological activity of 8-chloro-[1,2,4]triazolo [4,3-a]quinoxalines. J. Chem. Pharm. Res 2010; 2(1): 497-504.
56. Akio Kakefuda, Takeshi Suzuki, Takahiko Tobe, Junko Tsukada, Atsuo Tahara, Shuichi Sakamoto et al. Synthesis and pharmacological evaluation of 5-(4-biphenyl)-3-methyl-4-phenyl-1,2,4-triazole derivatives as a novel class of selective antagonists for the Human Vasopressin V_1A receptor. J. Med. Chem 2002; 45: 2589-2598.
57. Yan Ping Xu, Daniel Mayhugh, Ashraf Saeed, Xiao dong  Wang, Richard C. Thompson, Samuel J. Dominianni et al. Design and synthesis of a potent and selective triazolone-based peroxisome proliferator-activated receptor α agonist. J. Med. Chem 2003; 46: 5121-5124.
58. P. K. Goyal, A. Bhandari, A. C. Rana, C. B. Jain. Synthesis, Characterization and Analgesic Activity of some 4H-1, 2, 4-Triazole Derivatives.  Int. J. Chem. Tech Res 2010; 2(4):1992-1997.
    

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    How to cite this article:

    Kumudha D, Reddy RR and Kalavathi T: 1, 2, 4-Triazoles: As Biologically important Agents. Int J Pharm Sci Res. 3(12); 4562-4572.

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