Non-peptidic small-molecule inhibitors of the single-chain hepatitis C virus NS3 protease/NS4A cofactor complex discovered by structure-based NMR screening
…, A Arasappan, MM Senior, YS Wang…
Index: Wyss, Daniel F.; Arasappan, Ashok; Senior, Mary M.; Wang, Yu-Sen; Beyer, Brian M.; Njoroge, F. George; McCoy, Mark A. Journal of Medicinal Chemistry, 2004 , vol. 47, # 10 p. 2486 - 2498
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Citation Number: 58
Abstract
NMR-based screening of a customized fragment library identified 16 small-molecule hits that bind weakly (KD≈ 100 μM to 10 mM) to substrate binding sites of the NS4A-bound NS3 protease of the hepatitis C virus (HCV). Analogues for five classes of NMR hits were evaluated by a combination of NMR and biochemical data yielding SAR and, in most cases, optimized hits with improved potencies (KD≈ KI≈ 40 μM to 1 mM). NMR chemical shift ...
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[Hardcastle, Ian R.; Ahmed, Shafiq U.; Atkins, Helen; Farnie, Gillian; Golding, Bernard T.; Griffin, Roger J.; Guyenne, Sabrina; Hutton, Claire; Kaellblad, Per; Kemp, Stuart J.; Kitching, Martin S.; Newell, David R.; Norbedo, Stefano; Northen, Julian S.; Reid, Rebecca J.; Saravanan; Willems, Henriette M. G.; Lunec, John Journal of Medicinal Chemistry, 2006 , vol. 49, # 21 p. 6209 - 6221]