Inhibitors of hepatitis C virus NS3.4A protease 1. Non-charged tetrapeptide variants.

Perni, Robert B; Britt, Shawn D; Court, John C; Courtney, Lawrence F; Deininger, David D; Farmer, Luc J; Gates, Cynthia A; Harbeson, Scott L; Kim, Joseph L; Landro, James A; Levin, Rhonda B; Luong, Yu-Ping; O'Malley, Ethan T; Pitlik, Janos; Rao, B Govinda; Schairer, Wayne C; Thomson, John A; Tung, Roger D; Van Drie, John H; Wei, Yunyi

Perni, Robert B; Britt, Shawn D; Court, John C; Courtney, Lawrence F; Deininger, David D; Farmer, Luc J; Gates, Cynthia A; Harbeson, Scott L; Kim, Joseph L; Landro, James A; Levin, Rhonda B; Luong, Yu-Ping; O'Malley, Ethan T; Pitlik, Janos; Rao, B Govinda; Schairer, Wayne C; Thomson, John A; Tung, Roger D; Van Drie, John H; Wei, Yunyi.

Affiliation

Perni RB; Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA 02139, USA. robert_perni@vrtx.com

Bioorg Med Chem Lett ; 13(22): 4059-63, 2003 Nov 17.

Article in En | MEDLINE | ID: mdl-14592508

ABSTRACT

Tetrapeptide-based peptidomimetic compounds have been shown to effectively inhibit the hepatitis C virus NS3.4A protease without the need of a charged functionality. An aldehyde is used as a prototype reversible electrophilic warhead. The SAR of the P1 and P2 inhibitor positions is discussed.

Subject(s)

Hepacivirus/enzymology; Oligopeptides/chemical synthesis; Oligopeptides/pharmacology; Protease Inhibitors/chemical synthesis; Hepacivirus/drug effects; Kinetics; Models, Molecular; Protease Inhibitors/pharmacology; Protein Conformation; Structure-Activity Relationship; X-Ray Diffraction

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Collection: 01-internacional Database: MEDLINE Main subject: Oligopeptides / Protease Inhibitors / Hepacivirus Language: En Journal: Bioorg Med Chem Lett Journal subject: BIOQUIMICA / QUIMICA Year: 2003 Type: Article Affiliation country: United States

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