摘要:
A novel series of thiazolone-acylsulfonamides were designed as HCV NS5B polymerase allosteric inhibitors. The structure based drug designs (SBDD) were guided by docking results that revealed the potential to explore an additional pocket in the allosteric site. In particular, the designed molecules contain moieties of previously described thiazolone and a newly designed acylsulfonamide linker that is in turn connected with a substituted aromatic ring. The selected compounds were synthesized and demonstrated low mu M activity. The X-ray complex structure was determined at a 2.2 angstrom resolution and converged with the SBDD principle. (c) 2007 Elsevier Ltd. All rights reserved.