Nageswara Rao, Desaboini published the artcileDiscovery of Quinoxaline-Based P1-P3 Macrocyclic NS3/4A Protease Inhibitors with Potent Activity against Drug-Resistant Hepatitis C Virus Variants, Recommanded Product: 1-Methylcyclobutan-1-ol, the publication is Journal of Medicinal Chemistry (2021), 64(16), 11972-11989, database is CAplus and MEDLINE.
The three pan-genotypic HCV NS3/4A protease inhibitors (PIs) currently in clin. use-grazoprevir, glecaprevir, and voxilaprevir-are quinoxaline-based P2-P4 macrocycles and thus exhibit similar resistance profiles. Using our quinoxaline-based P1-P3 macrocyclic lead compounds as an alternative chem. scaffold, we explored structure-activity relationships (SARs) at the P2 and P4 positions to develop pan-genotypic PIs that avoid drug resistance. A structure-guided strategy was used to design and synthesize two series of compounds with different P2 quinoxalines in combination with diverse P4 groups of varying sizes and shapes, with and without fluorine substitutions. Our SAR data and cocrystal structures revealed the interplay between the P2 and P4 groups, which influenced inhibitor binding and the overall resistance profile. Optimizing inhibitor interactions in the S4 pocket led to PIs with excellent antiviral activity against clin. relevant PI-resistant HCV variants and genotype 3, providing potential pan-genotypic inhibitors with improved resistance profiles.
Journal of Medicinal Chemistry published new progress about 20117-47-9. 20117-47-9 belongs to alcohols-buliding-blocks, auxiliary class Aliphatic cyclic hydrocarbon,Alcohol, name is 1-Methylcyclobutan-1-ol, and the molecular formula is C5H10O, Recommanded Product: 1-Methylcyclobutan-1-ol.
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