Cummings, Maxwell D. published the artcileDiscovery and Early Development of TMC647055, a Non-Nucleoside Inhibitor of the Hepatitis C Virus NS5B Polymerase, Application of trimethyloxosulphonium chloride, the publication is Journal of Medicinal Chemistry (2014), 57(5), 1880-1892, database is CAplus and MEDLINE.
Structure-based macrocyclization of a 6-carboxylic acid indole chemotype has yielded potent and selective finger-loop inhibitors of the hepatitis C virus (HCV) NS5B polymerase. Lead optimization in conjunction with in vivo evaluation in rats identified several compounds showing (i) nanomolar potency in HCV replicon cells, (ii) limited toxicity and off-target activities, and (iii) encouraging preclin. pharmacokinetic profiles characterized by high liver distribution. This effort culminated in the identification of TMC647055 (I), a nonzwitterionic 17-membered-ring macrocycle characterized by high affinity, long polymerase residence time, and broad genotypic coverage. In vitro results of the combination of I with the HCV protease inhibitor TMC435 (simeprevir) supported an evaluation of this combination in patients with regard to virus suppression and resistance emergence. In a phase 1b trial with HCV genotype 1-infected patients, I was considered to be safe and well-tolerated and demonstrated potent antiviral activity, which was further enhanced in a combination study with TMC435.
Journal of Medicinal Chemistry published new progress about 5034-06-0. 5034-06-0 belongs to chlorides-buliding-blocks, auxiliary class Salt,Aliphatic hydrocarbon chain, name is trimethyloxosulphonium chloride, and the molecular formula is C3H9ClOS, Application of trimethyloxosulphonium chloride.
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