On March 13, 2014, Cummings, Maxwell D.; Lin, Tse-I.; Hu, Lili; Tahri, Abdellah; McGowan, David; Amssoms, Katie; Last, Stefaan; Devogelaere, Benoit; Rouan, Marie-Claude; Vijgen, Leen; Berke, Jan Martin; Dehertogh, Pascale; Fransen, Els; Cleiren, Erna; van der Helm, Liesbet; Fanning, Gregory; Nyanguile, Origene; Simmen, Kenny; Van Remoortere, Pieter; Raboisson, Pierre; Vendeville, Sandrine published an article.Application of 5034-06-0 The title of the article was Discovery and Early Development of TMC647055, a Non-Nucleoside Inhibitor of the Hepatitis C Virus NS5B Polymerase. And the article contained the following:
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. The experimental process involved the reaction of trimethyloxosulphonium chloride(cas: 5034-06-0).Application of 5034-06-0
The Article related to tmc647055 macrocyclic hepatitis c virus ns5b polymerase inhibitor preparation, antiviral activity pharmacokinetics biol evaluation tmc647055, Heterocyclic Compounds (More Than One Hetero Atom): Eight- and Higher-Membered Rings and other aspects.Application of 5034-06-0
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