Synthesis and evaluation of some new 1,3,4-oxadiazoles bearing thiophene, thiazole, coumarin, pyridine and pyridazine derivatives as antiviral agents

Open access

Abstract

In an attempt to produce heterocyclic compounds based on 1,3,4-oxadiazole derivatives with potential antiviral activity, synthesis of compound 1 [2-(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetonitrile] was performed through the reaction of cyanoacetic acid hydrazide with carbon disulfide in alcoholic potassium hydroxide. Compound 1 has an activating methylene group, so it was directed toward some specific reactions. Thus, aryldiazonium chlorides reacted with compound 1 affording hydrazono derivatives 2a-c. Also, aromatic aldehydes reacted with compound 1 to produce compounds 3a,b. Furthermore, cyclic ketones were subjected to the synthesis of fused thiophene derivatives 4a,b via reaction with compound 1 in the presence of elemental sulfur. In addition, 1,3,4-oxadiazole derivative 1, when reacted with isothiocyanates, salicylaldehyde or 1,3-dicarbonyl compounds, formed thiazole derivatives 5a,b, coumarin derivative 6 and alkenyl derivatives 7a,b resp. Compound 7b underwent cyclization to afford pyridine derivative 8. Arylhydrazono derivatives 9a,b were produced through the reaction of compound 7a with aryldiazonium chlorides. Products 9a,b underwent cyclization to produce pyridazine derivatives 10a,b. Finally, 1,3,4-oxadiazole derivative 1 was directed toward reaction with hydrazine derivatives, bromoacetophenone and ethylchloroacetate affording compounds 11a,b, 12 and 13, resp. Fused thiophene derivatives 14a,b were produced via reaction of compounds 4a,b with a mixture of malononitrile and ethylorthoformate. Antiviral activity of the synthesized products showed that 5-(4-amino-3-ethyl-2-thioxo-2,3-dihydrothiazol-5-yl)-1,3,4-oxadiazole-2(3H)-thione (5a) and 5-(4-amino-3-phenyl-2-thioxo-2,3-dihydrothiazol-5-yl)-1,3,4-oxadiazole-2(3H)-thione (5b) acted as the most active agents against Feline herpes virus, Feline corona virus, Herpes simplex virus-1 and Herpes simplex virus-2, whereas compound 2-(5-(2-phenylhydrazono)-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetonitrile (11b) was the most effective against Vaccinia virus, Herpes simplex virus (TK-KOS-ACVr), Coxsackie virus B4 and Vesicular stomatitis virus.

1. N. C. Desai, H. Somani, A. Trivedi, K. Bhatt, L. Nawale, V. M. Khedkar, P. C. Jha and D. Sarkar, Synthesis, biological evaluation and molecular docking study of some novel indole and pyridine based 1,3,4-oxadiazole derivatives as potential antitubercular agents, Bioorg. Med. Chem. Lett. 26 (2016) 1776–1783; https://doi.org/10.1016/j.bmcl.2016.02.043

2. A. G. Banerjee, N. Das, S. A. Shengule, R. S. Srivastava and S. K. Shrivastava, Synthesis, characterization, evaluation and molecular dynamics studies of 5,6-diphenyl-1,2,4-triazin-3(2H)-one derivatives bearing 5-substituted 1,3,4-oxadiazole as potential anti–inflammatory and analgesic agents, Eur. J. Med. Chem. 101 (2015) 81–95; https://doi.org/10.1016/j.ejmech.2015.06.020

3. W. Wu, Q. Chen, A. Tai, G. Jiang and G. Ouyang, Synthesis and antiviral activity of 2-substituted methylthio-5-(4-amino-2-methylpyrimidin-5-yl)-1,3,4-oxadiazole derivatives, Bioorg. Med. Chem. Lett. 25 (2015) 2243–2246; https://doi.org/10.1016/j.bmcl.2015.02.069

4. S. Zhang, Y. Luo, L. Q. He, Z. J. Liu, A. Q. Jiang, Y. H. Yang and H. L. Zhu, Synthesis, biological evaluation, and molecular docking studies of novel 1,3,4-oxadiazole derivatives possessing benzotriazole moiety as FAK inhibitors with anticancer activity, Bioorg. Med. Chem. 21 (2013) 3723–3729; https://doi.org/10.1016/j.bmc.2013.04.043

5. R. A. Rane, S. D. Gutte and N. U. Sahu, Synthesis and evaluation of novel 1,3,4-oxadiazole derivatives of marine bromopyrrole alkaloids as antimicrobial agent, Bioorg. Med. Chem. Lett. 22 (2012) 6429–6432; https://doi.org/10.1016/j.bmcl.2012.08.061

6. Y. Kotaiah, N. Harikrishna, K. Nagaraju and C. V. Rao, Synthesis and antioxidant activity of 1,3,4-oxadiazole tagged thieno[2,3-d]pyrimidine derivatives, Eur. J. Med. Chem. 58 (2012) 340–345; https://doi.org/10.1016/j.ejmech.2012.10.007

7. N. C. Desai, N. Bhatt, H. Somani and A. Trivedi, Synthesis, antimicrobial and cytotoxic activities of some novel thiazole clubbed 1,3,4-oxadiazoles, Eur. J. Med. Chem. 67 (2013) 54–59; https://doi.org/10.1016/j.ejmech.2013.06.029

8. M. Mahesh, G. Bheemaraju, G. Manjunath and P. V. Ramana, Synthesis of new oxadiazole, pyrazole and pyrazolin-5-one bearing 2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy) acetohydrazide analogs as potential antibacterial and antifungal agents, Ann. Pharm. Fran. 74 (2016) 34–44; https://doi.org/10.1016/j.pharma.2015.07.002

9. J. Wu, B. Song, H. Chen, P. Bhadury and D. Hu, Synthesis and antifungal activity of 5-chloro-6-phenylpyridazin-3(2H)-one derivatives, Molecules 14 (2009) 3676–3687; https://doi.org/10.3390/molecules14093676

10. J. D. S. Chaves, L. G. Tunes, C. H. de J. Franco, T. M. Francisco, C. C. Corrêa, S. M. F. Murta, R. L. Monte-Neto, H. Silva, A. P. S. Fontes and M. V. de Almeida, Novel gold(I) complexes with 5-phenyl-1,3,4-oxadiazole-2-thione and phosphine as potential anticancer and antileishmanial agents, Eur. J. Med. Chem. 127 (2017) 727–739; https://doi.org/10.1016/j.ejmech.2016.10.052

11. P. Puthiyapurayil, B. Poojary, C. Chikkanna and S. K. Buridipad, Design, synthesis and biological evaluation of a novel series of 1,3,4-oxadiazole bearing N-methyl-4-(trifluoromethyl)phenyl pyrazole moiety as cytotoxic agents, Eur. J. Med. Chem. 53 (2012) 203–210; https://doi.org/10.1016/j.ejmech.2012.03.056

12. S. Bansal, M. Bala, S. K. Suthar, S. Choudhary, S. Bhattacharya, V. Bhardwaj, S. Singla and A. Joseph, Design and synthesis of novel 2-phenyl-5-(1,3-diphenyl-1H-pyrazol-4-yl)-1,3,4-oxadiazoles as selective COX-2 inhibitors with potent anti-inflammatory activity, Eur. J. Med. Chem. 80 (2014) 167–174; https://doi.org/10.1016/j.ejmech.2014.04.045

13. S. R. Desai, U. Laddi, R. S. Bennur, P. A. Patil and S. Bennur, Synthesis and pharmacological activities of some new 5-substituted-2-mercapto-1,3,4-oxadiazoles, Indian J. Pharm. Sci. 73 (2011) 593–596; https://doi.org/10.4103/0250-474X.99025

14. E. De Clercq, T. Sakuma, M. Baba, R. Pauwels, J. Balzarini, I. Rosenberg and A. Holy, Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines, Antiviral Res. 8 (1987) 261–272; https://doi.org/10.1016/S0166-3542(87)80004-9

15. K. A. El-Sharkawy, N. N. E. El-Sayed and M. Y. Zaki, Uses of 2-amino-5,6-dihydro-4H-cyclopenta-[b]thiophene-3-carbonitrile in the synthesis of heterocyclic compounds with anticonvulsant, behavioral and CNS antidepressant activities, Int. Res. J. Pure Appl. Chem. 2 (2012) 91–104; https://doi.org/10.9734/IRJPAC/2012/1222

16. M. Albratty, K. A. El-Sharkawy and M. S. Alam, Synthesis and antitumor activity of some novel thiophene, pyrimidine, coumarin, pyrazole and pyridine derivatives, Acta Pharm. 67 (2017) 15–33; https://doi.org/10.1515/acph-2017-0004

Acta Pharmaceutica

The Journal of Croatian Pharmaceutical Society

Journal Information


IMPACT FACTOR 2018: 1,405
5-year IMPACT FACTOR: 1,701

CiteScore 2018: 1.47

SCImago Journal Rank (SJR) 2018: 0.314
Source Normalized Impact per Paper (SNIP) 2018: 0.637

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 509 509 265
PDF Downloads 200 200 60