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Synthesis and evaluation of some new 1,3,4-oxadiazoles bearing thiophene, thiazole, coumarin, pyridine and pyridazine derivatives as antiviral agents
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| Zeitschriftentitel: | Acta Pharmaceutica |
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| Personen und Körperschaften: | , , |
| In: | Acta Pharmaceutica, 69, 2019, 2, S. 261-276 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Walter de Gruyter GmbH
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| Schlagwörter: |
| Zusammenfassung: | <jats:title>Abstract</jats:title> <jats:p>In an attempt to produce heterocyclic compounds based on 1,3,4-oxadiazole derivatives with potential antiviral activity, synthesis of compound <jats:bold>1</jats: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 <jats:bold>1</jats:bold> has an activating methylene group, so it was directed toward some specific reactions. Thus, aryldiazonium chlorides reacted with compound <jats:bold>1</jats:bold> affording hydrazono derivatives <jats:bold>2a-c</jats:bold>. Also, aromatic aldehydes reacted with compound <jats:bold>1</jats:bold> to produce compounds <jats:bold>3a</jats:bold>,<jats:bold>b</jats:bold>. Furthermore, cyclic ketones were subjected to the synthesis of fused thiophene derivatives <jats:bold>4a,b</jats:bold> <jats:italic>via</jats:italic> reaction with compound <jats:bold>1</jats:bold> in the presence of elemental sulfur. In addition, 1,3,4-oxadiazole derivative <jats:bold>1,</jats:bold> when reacted with isothiocyanates, salicylaldehyde or 1,3-dicarbonyl compounds, formed thiazole derivatives <jats:bold>5a</jats:bold>,<jats:bold>b</jats:bold>, coumarin derivative <jats:bold>6</jats:bold> and alkenyl derivatives <jats:bold>7a</jats:bold>,<jats:bold>b</jats:bold> resp. Compound <jats:bold>7b</jats:bold> underwent cyclization to afford pyridine derivative <jats:bold>8</jats:bold>. Arylhydrazono derivatives <jats:bold>9a</jats:bold>,<jats:bold>b</jats:bold> were produced through the reaction of compound <jats:bold>7a</jats:bold> with aryldiazonium chlorides. Products <jats:bold>9a</jats:bold>,<jats:bold>b</jats:bold> underwent cyclization to produce pyridazine derivatives <jats:bold>10a</jats:bold>,<jats:bold>b</jats:bold>. Finally, 1,3,4-oxadiazole derivative <jats:bold>1</jats:bold> was directed toward reaction with hydrazine derivatives, bromoacetophenone and ethylchloroacetate affording compounds <jats:bold>11a</jats:bold>,<jats:bold>b</jats:bold>, <jats:bold>12</jats:bold> and <jats:bold>13</jats:bold>, resp. Fused thiophene derivatives <jats:bold>14a</jats:bold>,<jats:bold>b</jats:bold> were produced <jats:italic>via</jats:italic> reaction of compounds <jats:bold>4a</jats:bold>,<jats:bold>b</jats: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<jats:italic>H</jats:italic>)-thione (<jats:bold>5a</jats:bold>) and 5-(4-amino-3-phenyl-2-thioxo-2,3-dihydrothiazol-5-yl)-1,3,4-oxadiazole-2(3<jats:italic>H</jats:italic>)-thione (<jats:bold>5b</jats:bold>) acted as the most active agents against <jats:italic>Feline herpes virus, Feline corona virus</jats:italic>, <jats:italic>Herpes simplex virus-1</jats:italic> and <jats:italic>Herpes simplex virus-2</jats:italic>, whereas compound 2-(5-(2-phenylhydrazono)-4,5-dihydro-1,3,4-oxadiazol-2-yl)acetonitrile (<jats:bold>11b</jats:bold>) was the most effective against <jats:italic>Vaccinia virus</jats:italic>, <jats:italic>Herpes simplex virus</jats:italic> (TK-KOS-ACVr), <jats:italic>Coxsackie virus B4</jats:italic> and <jats:italic>Vesicular stomatitis virus</jats:italic>.</jats:p> |
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| Umfang: | 261-276 |
| ISSN: |
1846-9558
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| DOI: | 10.2478/acph-2019-0015 |