Inhibitors of Hepatitis C Virus NS3.4A Protease: P2 Proline Variants

Luc J. Farmer; Shawn D. Britt; Kevin M. Cottrell; John J. Court; Lawrence F. Courtney; David D. Deininger; Cynthia A. Gates; Scott L. Harbeson; Kai Lin; Chao Lin; Yu- P. Luong; John P. Maxwell; Janos Pitlik; B. G. Rao; Wayne C. Schairer; John A. Thomson; Roger D. Tung; John H. Van Drie; Yunyi Wei; Robert B. Perni

doi:10.2174/157018005774479203

ISSN: 1570-1808
E-ISSN: 1875-628X

Inhibitors of Hepatitis C Virus NS3.4A Protease: P2 Proline Variants
Authors: Luc J. Farmer¹, Shawn D. Britt², Kevin M. Cottrell³, John J. Court⁴, Lawrence F. Courtney⁵, David D. Deininger⁶, Cynthia A. Gates⁷, Scott L. Harbeson⁸, Kai Lin⁹, Chao Lin¹⁰, Yu- P. Luong¹¹, John P. Maxwell¹², Janos Pitlik¹³, B. G. Rao¹⁴, Wayne C. Schairer¹⁵, John A. Thomson¹⁶, Roger D. Tung¹⁷, John H. Van Drie¹⁸, Yunyi Wei¹⁹ and Robert B. Perni²⁰
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¹ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ² Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ³ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ⁴ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ⁵ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ⁶ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ⁷ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ⁸ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ⁹ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ¹⁰ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ¹¹ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ¹² Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ¹³ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ¹⁴ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ¹⁵ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ¹⁶ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ¹⁷ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ¹⁸ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ¹⁹ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA ²⁰ Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA, 02139, USA
Source: Letters in Drug Design & Discovery, Volume 2, Issue 7, Nov 2005, p. 497 - 502
DOI: https://doi.org/10.2174/157018005774479203
- Available online: 01 Nov 2005

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Abstract

A series of novel bicyclic proline P2 scaffold based tetrapeptide inhibitors were designed and prepared. Given their relatively small size, these compounds exhibited exceptional binding affinities and good cellular potencies for HCV protease. One of the best analogues, tricyclic based P2 scaffold 12, had an affinity for HCV with a Ki of 37 nM and cell activity IC50 of 200 nM.

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2005-11-01

2025-05-26

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Article Type: Research Article

Keyword(s): Hepatitis C; NS3•4A protease; P2 scaffolds; tetrapeptide inhibitors; VX-950, bicyclic proline

Inhibitors of Hepatitis C Virus NS3.4A Protease: P2 Proline Variants

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