<abstract xmlns="http://www.w3.org/1999/xhtml"><p>In an attempt to produce heterocyclic compounds based on 1,3,4-oxadiazole derivatives with potential antiviral activity, synthesis of compound <bold>1</bold> [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 <bold>1</bold> has an activating methylene group, so it was directed toward some specific reactions. Thus, aryldiazonium chlorides reacted with compound <bold>1</bold> affording hydrazono derivatives <bold>2a-c</bold>. Also, aromatic aldehydes reacted with compound <bold>1</bold> to produce compounds <bold>3a</bold>,<bold>b</bold>. Furthermore, cyclic ketones were subjected to the synthesis of fused thiophene derivatives <bold>4a,b</bold><italic>via</italic> reaction with compound <bold>1</bold> in the presence of elemental sulfur. In addition, 1,3,4-oxadiazole derivative <bold>1,</bold> when reacted with isothiocyanates, salicylaldehyde or 1,3-dicarbonyl compounds, formed thiazole derivatives <bold>5a</bold>,<bold>b</bold>, coumarin derivative <bold>6</bold> and alkenyl derivatives <bold>7a</bold>,<bold>b</bold> resp. Compound <bold>7b</bold> underwent cyclization to afford pyridine derivative <bold>8</bold>. Arylhydrazono derivatives <bold>9a</bold>,<bold>b</bold> were produced through the reaction of compound <bold>7a</bold> with aryldiazonium chlorides. Products <bold>9a</bold>,<bold>b</bold> underwent cyclization to produce pyridazine derivatives <bold>10a</bold>,<bold>b</bold>. Finally, 1,3,4-oxadiazole derivative <bold>1</bold> was directed toward reaction with hydrazine derivatives, bromoacetophenone and ethylchloroacetate affording compounds <bold>11a</bold>,<bold>b</bold>, <bold>12</bold> and <bold>13</bold>, resp. Fused thiophene derivatives <bold>14a</bold>,<bold>b</bold> were produced <italic>via</italic> reaction of compounds <bold>4a</bold>,<bold>b</bold> 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(3<italic>H</italic>)-thione (<bold>5a</bold>) and 5-(4-amino-3-phenyl-2-thioxo-2,3-dihydrothiazol-5-yl)-1,3,4-oxadiazole-2(3<italic>H</italic>)-thione (<bold>5b</bold>) acted as the most active agents against <italic>Feline herpes virus, Feline corona virus</italic>, <italic>Herpes simplex virus-1</italic> and <italic>Herpes simplex virus-2</italic>, whereas compound 2-(5-(2-phenylhydrazono)-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetonitrile (<bold>11b</bold>) was the most effective against <italic>Vaccinia virus</italic>, <italic>Herpes simplex virus</italic> (TK-KOS-ACVr), <italic>Coxsackie virus B4</italic> and <italic>Vesicular stomatitis virus</italic>.</p></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,bvia 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.

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

Faculty of Biotechnology October University for Modern Sciences and Arts (MSA)

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

In an attempt to produce heterocyclic compounds based on 1,3,4-oxadiazole derivatives with potential antiviral activity, synthesis of compound 1...

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

Published Online: Mar 28, 2019

Page range: 261 - 276

Accepted: Nov 05, 2018

DOI: https://doi.org/10.2478/acph-2019-0015

Keywords
1,3,4-oxadiazole derivatives, thiophene, coumarin, thiazole, pyridine, pyridazine, antiviral activity

© 2019 Mohammed Albratty et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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

Published Online: Mar 28, 2019

Page range: 261 - 276

Accepted: Nov 05, 2018

DOI: https://doi.org/10.2478/acph-2019-0015

Keywords1,3,4-oxadiazole derivatives, thiophene, coumarin, thiazole, pyridine, pyridazine, antiviral activity

© 2019 Mohammed Albratty et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
1,3,4-oxadiazole derivatives, thiophene, coumarin, thiazole, pyridine, pyridazine, antiviral activity