20896-44-0Relevant articles and documents
Des-A-ring benzothiadiazines: Inhibitors of HCV genotype 1 NS5B RNA-dependent RNA polymerase
Donner, Pamela L.,Xie, Qinghua,Pratt, John K.,Maring, Clarence J.,Kati, Warren,Jiang, Wen,Liu, Yaya,Koev, Gennadiy,Masse, Sherie,Montgomery, Debra,Molla, Akhter,Kempf, Dale J.
, p. 2735 - 2738 (2008)
In our program to discover non-nucleoside, small molecule inhibitors of genotype 1 HCV polymerase, we investigated a series of promising analogs based on a benzothiadiazine screening hit that contains an ABCD ring system. After demonstrating that a methyl
FUSED [1,2,4]THIADIAZINE DERIVATIVES WHICH ACT AS KAT INHIBITORS OF THE MYST FAMILY
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Page/Page column 188, (2019/03/17)
A compound of formula (I): which inhibits the activity of one or more KATs of the MYST family, i.e., TIP60, KAT6B, MOZ, HBO1 and MOF.
Integrated structure-based activity prediction model of benzothiadiazines on various genotypes of HCV NS5b polymerase (1a, 1b and 4) and its application in the discovery of new derivatives
Ismail, Mohamed A.H.,Abou El Ella, Dalal A.,Abouzid, Khaled A.M.,Mahmoud, Amr H.
supporting information; experimental part, p. 2455 - 2478 (2012/05/05)
This work presents the first structure-based activity prediction model for benzothiadiazines against various genotypes of HCV NS5b polymerase (1a, 1b and 4).The model is a comprehensive workflow of structure-based field template followed by guided docking. The field template was used as a pre-filter and a tool to provide hits in good orientation and position. It was created based on detailed molecular interaction field analysis which includes Topomer CoMFA, grid independent analysis and Superstar. On the other hand, Guided docking was used as a refinement and assessment tool. It was actively directed by two scores: Moldock score as an interaction descriptor (r2 = 0.65) and a template similarity score as a measure for accurate binding-mode compliance. The docking template was based on energy-based pharmacophore analysis. The whole procedure was formulated and tweaked for both screening (ROC of AUC = 0.91) and activity prediction (r2 of 0.8) for the genotype 1a. In order to widen the model scope, linear interaction energy was used as a tool for predicting activities of other genotypes based on the docked ligand poses while mutation binding energy was used to investigate the effect of each amino acid mutation in genotype 4. The model was applied for structure-based fragment hopping by screening a library designed by reaction enumeration. A top scoring hit was used to generate a focused library such that it has lower TPSA than the original class ligands and thus better pharmacokinetic properties. After that, experimental validation was carried out by the synthesis of this library and its biological evaluation which yielded compounds that exhibit EC50 ranging from 1.86 to 23 μM.
4-Hydroxy-5,6-dihydro-1H-pyridin-2-one compounds
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Page/Page column 20, (2009/04/24)
The invention is directed to 4-hydroxy-5,6-dihydro-1H-pyridin-2-one compounds and pharmaceutical compositions containing such compounds that are useful in treating infections by hepatitis C virus.