Discovery of Ruzasvir (MK-8408): A Potent, Pan-Genotype HCV NS5A Inhibitor with Optimized Activity against Common Resistance-Associated Polymorphisms.
| Autor: | Tong L, Yu W, Chen L, Selyutin O, Dwyer MP, Nair AG, Mazzola R, Kim JH, Sha D, Yin J, Ruck RT, Davies IW, Hu B; Department of Medicinal Chemistry, WuXi AppTec , Shanghai, 200131, China., Zhong B; Department of Medicinal Chemistry, WuXi AppTec , Shanghai, 200131, China., Hao J; Department of Medicinal Chemistry, WuXi AppTec , Shanghai, 200131, China., Ji T; Department of Medicinal Chemistry, WuXi AppTec , Shanghai, 200131, China., Zan S; Department of Medicinal Chemistry, WuXi AppTec , Shanghai, 200131, China., Liu R, Agrawal S, Xia E, Curry S, McMonagle P, Bystol K, Lahser F, Carr D, Rokosz L, Ingravallo P, Chen S, Feng KI, Cartwright M, Asante-Appiah E, Kozlowski JA |
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| Jazyk: | angličtina |
| Zdroj: | Journal of medicinal chemistry [J Med Chem] 2017 Jan 12; Vol. 60 (1), pp. 290-306. Date of Electronic Publication: 2016 Nov 15. |
| DOI: | 10.1021/acs.jmedchem.6b01310 |
| Abstrakt: | We describe the research that led to the discovery of compound 40 (ruzasvir, MK-8408), a pan-genotypic HCV nonstructural protein 5A (NS5A) inhibitor with a "flat" GT1 mutant profile. This NS5A inhibitor contains a unique tetracyclic indole core while maintaining the imidazole-proline-valine Moc motifs of our previous NS5A inhibitors. Compound 40 is currently in early clinical trials and is under evaluation as part of an all-oral DAA regimen for the treatment of chronic HCV infection. |
| Databáze: | MEDLINE |
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