56759-34-3Relevant academic research and scientific papers
Synthesis, biological evaluation and in silico modeling of novel pan-genotypic NS5A inhibitors
Aladinskiy, Vladimir A.,Ivanenkov, Yan A.,Ivashchenko, Alexander V.,Ivashchenko, Andrey A.,Karapetian, Ruben N.,Koryakova, Angela G.,Kravchenko, Dmitry V.,Mitkin, Oleg D.,Ryakhovskiy, Alexey A.,Savchuk, Nikolai P.,Zagribelnyy, Bogdan A.
supporting information, (2020/09/01)
A series of novel small-molecule pan-genotypic hepatitis C virus (HCV) NS5A inhibitors with picomolar activity containing 2-[(2S)-pyrrolidin-2-yl]-5-[4-(4-{2-[(2S)-pyrrolidin-2-yl]-1H-imidazol-5-yl}buta-1,3-diyn-1-yl)phenyl]-1H-imidazole core was designed based on molecular modeling study and SAR analysis. The constructed in silico model and docking study provide a deep insight into the binding mode of this type of NS5A inhibitors. Based on the predicted binding interface we have prioritized the most crucial diversity points responsible for improving antiviral activity. The synthesized molecules were tested in a cell-based assay, and compound 1.12 showed an EC50 value in the range of 2.9–34 pM against six genotypes of NS5A HCV, including gT3a, and demonstrated favorable pharmacokinetic profile in rats. This lead compound can be considered as an attractive candidate for further clinical evaluation.
PAN-GENOMIC INHIBITORS OF NS5A PROTEIN ENCODED BY HCV, PHARMACEUTICAL COMPOSITIONS, INTERMEDIATES FOR INHIBITOR SYNTHESIS, AND THEIR SYNTHESIS AND APPLICATION METHODS.
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Page/Page column 39-40; 63-64, (2017/03/21)
Compound represented by formula 1 : or a pharmaceutically acceptable salt, a hydrate, a crystalline form, or a stereoisomer thereof, wherein: where R11 is an optionally substituted C1-C6 alkyl, an optionally substituted C3-C6 cycloalkyl, or an optionally substituted C1-C6 alkyloxy, and arrows (1-C4alkyl; R3 is an optionally substituted aryl, an optionally substituted aryloxy, an optionally substituted arylsulfanyl, an optionally substituted arylamino, or an optionally substituted nitrogen hetaryl; where R41 is an optionally substituted C1-C6 alkyl, an optionally substituted C3-C6 cycloalkyl, or an optionally substituted C1-C6 alkyloxy; X is buta-1,3-diynylene or 1,4-phenylene; arrows (— ) indicate the position of substituents attachment.
