Hepatitis C virus NS3-4A serine protease inhibitors: use of a P2-P1 cyclopropyl alanine combination for improved potency

S Bogen; A K Saksena; A Arasappan; H Gu; F G Njoroge; V Girijavallabhan; J Pichardo; N Butkiewicz; A Prongay; V Madison

doi:10.1016/j.bmcl.2005.07.009

Hepatitis C virus NS3-4A serine protease inhibitors: use of a P2-P1 cyclopropyl alanine combination for improved potency

Bioorg Med Chem Lett. 2005 Oct 15;15(20):4515-9. doi: 10.1016/j.bmcl.2005.07.009.

Authors

S Bogen¹, A K Saksena, A Arasappan, H Gu, F G Njoroge, V Girijavallabhan, J Pichardo, N Butkiewicz, A Prongay, V Madison

Affiliation

¹ Chemical Research, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. [email protected]

PMID: 16112862
DOI: 10.1016/j.bmcl.2005.07.009

Abstract

Modification of the P(2) and P(1) side chains of earlier P(3)-capped alpha-ketoamide inhibitor of HCV NS3 serine protease 1 resulted in the discovery of compound 24 with about 10-fold improvement in potency.

MeSH terms

Alanine / chemistry*
Serine Proteinase Inhibitors / chemistry*
Serine Proteinase Inhibitors / pharmacology*
Viral Nonstructural Proteins / antagonists & inhibitors*
X-Ray Diffraction

Substances

NS3 protein, hepatitis C virus
Serine Proteinase Inhibitors
Viral Nonstructural Proteins
Alanine