Proline-Based Allosteric Inhibitors of Zika and Dengue Virus NS2B/NS3 Proteases was written by Millies, Benedikt;von Hammerstein, Franziska;Gellert, Andrea;Hammerschmidt, Stefan;Barthels, Fabian;Goeppel, Ulrike;Immerheiser, Melissa;Elgner, Fabian;Jung, Nathalie;Basic, Michael;Kersten, Christian;Kiefer, Werner;Bodem, Jochen;Hildt, Eberhard;Windbergs, Maike;Hellmich, Ute A.;Schirmeister, Tanja. And the article was included in Journal of Medicinal Chemistry in 2019.Related Products of 6294-52-6 This article mentions the following:
The NS2B/NS3 serine proteases of the Zika and Dengue flaviviruses are attractive targets for the development of antiviral drugs. We report the synthesis and evaluation of a new, proline-based compound class that displays allosteric inhibition of both proteases. The structural features relevant for protease binding and inhibition were determined to establish them as new lead compounds for flaviviral inhibitors. Based on our structure-activity relationship studies, the mols. were further optimized, leading to inhibitors with submicromolar IC50 values and improved lipophilic ligand efficiency. The allosteric binding site in the proteases was probed using mutagenesis and covalent modification of the obtained cysteine mutants with maleimides, followed by computational elucidation of the possible binding modes. In infected cells, antiviral activity against Dengue virus serotype 2 using prodrugs of the inhibitors was observed In summary, a novel inhibitor scaffold targeting an allosteric site shared between flaviviral NS2B/NS3 proteases is presented whose efficacy is demonstrated in vitro and in cellulo. In the experiment, the researchers used many compounds, for example, 5,6-Dimethoxybenzo[d]thiazol-2-amine (cas: 6294-52-6Related Products of 6294-52-6).
5,6-Dimethoxybenzo[d]thiazol-2-amine (cas: 6294-52-6) belongs to thiazole derivatives. Thiazole rings are planar and aromatic. Thiazoles are characterized by larger pi-electron delocalization than the corresponding oxazoles and have therefore greater aromaticity. The nitrogen in thiazole is sp2 hybridized and the lone pair of electrons localized on the nitrogen is less reactive due to increased aromatic character and decreased basicity. It is protonated and alkylated/acylated at nitrogen forming hydrochloride and quaternary thiazolium salt.Related Products of 6294-52-6
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica