2514-36-5Relevant articles and documents
Structure-Guided Discovery of the Novel Covalent Allosteric Site and Covalent Inhibitors of Fructose-1,6-Bisphosphate Aldolase to Overcome the Azole Resistance of Candidiasis
Cao, Hongxuan,Chen, Han,Han, Xinya,Huang, Yunyuan,Liu, Jiaqi,Peng, Chao,Rao, Li,Ren, Yanliang,Sheng, Chunquan,Su, Chen,Tu, Jie,Wan, Chen,Wan, Jian,Wen, Wuqiang
, p. 2656 - 2674 (2022/02/09)
Fructose-1,6-bisphosphate aldolase (FBA) represents an attractive new antifungal target. Here, we employed a structure-based optimization strategy to discover a novel covalent binding site (C292 site) and the first-in-class covalent allosteric inhibitors
Facile synthesis and in vitro activity of n-substituted 1,2-benzisothiazol-3(2H)-ones against dengue virus NS2BNS3 protease
Batool, Farwa,Saeed, Muhammad,Saleem, Hafiza Nosheen,Kirschner, Luisa,Bodem, Jochen
, (2021/04/28)
Several new N-substituted 1,2-benzisothiazol-3(2H)-ones (BITs) were synthesised through a facile synthetic route for testing their anti-dengue protease inhibition. Contrary to the conventional multistep synthesis, we achieved structurally diverse BITs with excellent yields using a two-step, one-pot reaction strategy. All the synthesised compounds were prescreened for drug-like properties using the online Swiss Absorption, Distribution, Metabolism and Elimination (SwissADME) model, indicating their favourable pharmaceutical properties. Thus, the synthesised BITs were tested for inhibitory activity against the recombinant dengue virus serotype-2 (DENV-2) NS2BNS3 protease. Dose–response experiments and computational docking analyses revealed that several BITs bind to the protease in the vicinity of the catalytic triad with IC50 values in the micromolar range. The DENV2 infection assay showed that two BITs, 2-(2-chlorophenyl)benzo[d]isothiazol-3(2H)-one and 2-(2,6-dichlorophenyl)benzo[d]isothiazol-3(2H)-one, could suppress DENV replication and virus infectivity. These results indicate the potential of BITs for developing new anti-dengue therapeutics.
Novel synthesis method of N-substituted benzisothiazoline-3-ketone derivative
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Paragraph 0056-0058, (2020/07/02)
The invention discloses a novel synthesis method of an N-substituted benzisothiazoline-3-ketone derivative. The preparation method comprises the following steps: by taking a dithiosalicylic acid derivative and sulfur as raw materials, introducing chlorine or bromine to obtain a halogenated thiobenzoyl halide derivative, then preferably dropwise adding a mixed solution of primary amine and tertiaryamine, and carrying out reaction and ring closing to obtain the N-substituted benzisothiazole-3-ketone. The method disclosed by the invention is simple in process, safe and controllable, and easy forindustrial large-scale production.