Medicinal Chemistry: Synthesis and Pharmacochemical Investigation of Some Novel 1, 2, 4‐4H‐triazoles with Potential Antiviral Activity
Identifieur interne : 001A99 ( Main/Exploration ); précédent : 001A98; suivant : 001B00Medicinal Chemistry: Synthesis and Pharmacochemical Investigation of Some Novel 1, 2, 4‐4H‐triazoles with Potential Antiviral Activity
Auteurs : Spyroula S. Papakonstantinou-Garoufalia [Grèce] ; Ekaterini Tani [Grèce] ; Ourania Todoulou [Grèce] ; Aspasia Papadaki-Valiraki [Grèce] ; Evagelos Filippatos [Grèce] ; Erik De Clercq [Belgique] ; Panos N. Kourounakis [Grèce]Source :
- Journal of Pharmacy and Pharmacology [ 0022-3573 ] ; 1998-01.
English descriptors
- Teeft :
- Active oxygen species, Alogp, Alogp values, Anal, Antioxidant, Antioxidant activity, Antiviral, Antiviral activity, Biological activity, Chem, Compound, Derivative, Dmso, Etoh, Hydroxyl radicals, Lipid, Lipid peroxidation, Lipophilicity, Och3, Peroxidation, Piperazine, Reaction mixture, Same method, Test compounds.
Abstract
We report the synthesis of some mercaptotriazole derivatives in an effort to discover underlying structural requirements for antiviral activity. A preliminary antiviral study was performed and the contribution of the compounds to free radical processes was investigated. Because lipophilicity influences both biological activity and antioxidant potential we calculated lipophilicity and attempted to correlate this with antioxidant activity. Treatment of the N‐(aryl)piperazineacetohydrazides (compounds 1) with 2, 4‐dichloro‐phenylisothiocyanate gave the N‐(aryl)piperazinethiosemicarbazides (compounds 2) in good yield. Cyclization of these compounds after treatment with NaOH solution provided the corresponding 5‐(4‐aryl‐1‐piperazinylmethyl)‐4‐(2, 4‐dichlorophenyl)‐4H‐1, 2, 4‐triazole‐3‐thiols (compounds 3) in good yield. Reaction of compounds 3 with 2, 4‐dichloro‐or 4‐fluorobenzyl chloride in acetone in the presence of potassium carbonate gave the target compounds (compounds 4) in about 70% yield. The antioxidant effect of the compounds on non‐enzymatic lipid peroxidation of rat hepatic microsomal membranes was studied. Most of the examined compounds were active at concentration of 0.1 mM and most were found to prevent dimethylsulphoxide oxidation moderately (20–50%) at a concentration tenfold less than that of dimethylsulphoxide. The interaction of the synthesized compounds with 1, 1‐diphenyl‐2‐picrylhydrazyl stable free radical was also studied. Correlation was found between the two expressions of calculated lipophilicity, antioxidant activity and the lipophilicity of the synthesized compounds, and a correlation was derived between antioxidant activity and logP, which expresses the compounds' hydrogenbonding capacity.
Url:
DOI: 10.1111/j.2042-7158.1998.tb03313.x
Affiliations:
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A preliminary antiviral study was performed and the contribution of the compounds to free radical processes was investigated. Because lipophilicity influences both biological activity and antioxidant potential we calculated lipophilicity and attempted to correlate this with antioxidant activity. Treatment of the N‐(aryl)piperazineacetohydrazides (compounds 1) with 2, 4‐dichloro‐phenylisothiocyanate gave the N‐(aryl)piperazinethiosemicarbazides (compounds 2) in good yield. Cyclization of these compounds after treatment with NaOH solution provided the corresponding 5‐(4‐aryl‐1‐piperazinylmethyl)‐4‐(2, 4‐dichlorophenyl)‐4H‐1, 2, 4‐triazole‐3‐thiols (compounds 3) in good yield. Reaction of compounds 3 with 2, 4‐dichloro‐or 4‐fluorobenzyl chloride in acetone in the presence of potassium carbonate gave the target compounds (compounds 4) in about 70% yield. The antioxidant effect of the compounds on non‐enzymatic lipid peroxidation of rat hepatic microsomal membranes was studied. Most of the examined compounds were active at concentration of 0.1 mM and most were found to prevent dimethylsulphoxide oxidation moderately (20–50%) at a concentration tenfold less than that of dimethylsulphoxide. The interaction of the synthesized compounds with 1, 1‐diphenyl‐2‐picrylhydrazyl stable free radical was also studied. Correlation was found between the two expressions of calculated lipophilicity, antioxidant activity and the lipophilicity of the synthesized compounds, and a correlation was derived between antioxidant activity and logP, which expresses the compounds' hydrogenbonding capacity.</div></front></TEI><affiliations><list><country><li>Belgique</li><li>Grèce</li></country><region><li>Province du Brabant flamand</li><li>Région flamande</li></region><settlement><li>Louvain</li></settlement><orgName><li>Katholieke Universiteit Leuven</li></orgName></list><tree><country name="Grèce"><noRegion><name sortKey="Papakonstantinou Aroufalia, Spyroula S" sort="Papakonstantinou Aroufalia, Spyroula S" uniqKey="Papakonstantinou Aroufalia S" first="Spyroula S." last="Papakonstantinou-Garoufalia">Spyroula S. Papakonstantinou-Garoufalia</name></noRegion><name sortKey="Filippatos, Evagelos" sort="Filippatos, Evagelos" uniqKey="Filippatos E" first="Evagelos" last="Filippatos">Evagelos Filippatos</name><name sortKey="Kourounakis, Panos N" sort="Kourounakis, Panos N" uniqKey="Kourounakis P" first="Panos N." last="Kourounakis">Panos N. Kourounakis</name><name sortKey="Kourounakis, Panos N" sort="Kourounakis, Panos N" uniqKey="Kourounakis P" first="Panos N." last="Kourounakis">Panos N. Kourounakis</name><name sortKey="Papadaki Aliraki, Aspasia" sort="Papadaki Aliraki, Aspasia" uniqKey="Papadaki Aliraki A" first="Aspasia" last="Papadaki-Valiraki">Aspasia Papadaki-Valiraki</name><name sortKey="Tani, Ekaterini" sort="Tani, Ekaterini" uniqKey="Tani E" first="Ekaterini" last="Tani">Ekaterini Tani</name><name sortKey="Todoulou, Ourania" sort="Todoulou, Ourania" uniqKey="Todoulou O" first="Ourania" last="Todoulou">Ourania Todoulou</name></country><country name="Belgique"><region name="Région flamande"><name sortKey="De Clercq, Erik" sort="De Clercq, Erik" uniqKey="De Clercq E" first="Erik" last="De Clercq">Erik De Clercq</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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