Development of the 1,2,4-triazole-based anticonvulsant drug candidates acting on the voltage-gated sodium channels. Insights from in-vivo, in-vitro, and in-silico studies was written by Kapron, Barbara;Luszczki, Jarogniew J.;Plazinska, Anita;Siwek, Agata;Karcz, Tadeusz;Grybos, Anna;Nowak, Gabriel;Makuch-Kocka, Anna;Walczak, Katarzyna;Langner, Ewa;Szalast, Karolina;Marciniak, Sebastian;Paczkowska, Magdalena;Cielecka-Piontek, Judyta;Ciesla, Lukasz M.;Plech, Tomasz. And the article was included in European Journal of Pharmaceutical Sciences in 2019.Synthetic Route of C4H7NS The following contents are mentioned in the article:
The treatment of epilepsy remains difficult mostly since almost 30% of patients suffer from pharmacoresistant forms of the disease. Therefore, there is an urgent need to search for new antiepileptic drug candidates. Previously, it has been shown that 4-alkyl-5-substituted-1,2,4-triazole-3-thione derivativatives possessed strong anticonvulsant activity in a maximal electroshock-induced seizure model of epilepsy. In this work, we examined the effect of the chem. structure of the 1,2,4-triazole-3-thione-based mols. on the anticonvulsant activity and the binding to voltage-gated sodium channels (VGSCs) and GABAA receptors. Docking simulations allowed us to determine the mode of interactions between the investigated compounds and binding cavity of the human VGSC. Selected compounds were also investigated in a panel of ADME-Tox assays, including parallel artificial membrane permeability assay (PAMPA), single cell gel electrophoresis (SCGE) and cytotoxicity evaluation in HepG2 cells. The obtained results indicated that unbranched alkyl chains, from Bu to hexyl, attached to 1,2,4-triazole core are essential both for good anticonvulsant activity and strong interactions with VGSCs. The combined in-vivo, in-vitro and in-silico studies emphasize 4-alkyl-5-substituted-1,2,4-triazole-3-thiones as promising agents in the development of new anticonvulsants. This study involved multiple reactions and reactants, such as Isopropylisothiocyanate (cas: 2253-73-8Synthetic Route of C4H7NS).
Isopropylisothiocyanate (cas: 2253-73-8) belongs to esters. Esters perform as high-grade solvents for a broad array of plastics, plasticizers, resins, and lacquers, and are one of the largest classes of synthetic lubricants on the commercial market. Polyesters are important plastics, with monomers linked by ester moieties. Esters contain a carbonyl center, which gives rise to 120° C–C–O and O–C–O angles. Unlike amides, esters are structurally flexible functional groups because rotation about the C–O–C bonds has a low barrier. Their flexibility and low polarity is manifested in their physical properties; they tend to be less rigid (lower melting point) and more volatile (lower boiling point) than the corresponding amides. Synthetic Route of C4H7NS
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Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics