1.
J Med Chem
; 49(11): 3052-5, 2006 Jun 01.
Article
in English
| MEDLINE
| ID: mdl-16722622
ABSTRACT
Through high throughput screening, substituted proline sulfonamide 6 was identified as HCV NS5b RNA-dependent RNA polymerase inhibitor. Optimization of various regions of the lead molecule resulted in compounds that displayed good potency and selectivity. The crystal structure of 6 and NS5b polymerase complex confirmed the binding near the active site region. The optimization approach and SAR are discussed in detail.
Subject(s)
Antiviral Agents/chemical synthesis , Proline/analogs & derivatives , Proline/chemical synthesis , Sulfonamides/chemical synthesis , Viral Nonstructural Proteins/antagonists & inhibitors , Viral Nonstructural Proteins/chemistry , Antiviral Agents/chemistry , Binding Sites , Crystallography, X-Ray , Models, Molecular , Molecular Conformation , Proline/chemistry , Structure-Activity Relationship , Sulfonamides/chemistry
2.
J Biomol NMR
; 28(4): 409-10, 2004 Apr.
Article
in English
| MEDLINE
| ID: mdl-14872136