Abstract
We describe herein tetrapeptidyl α-ketoamide 4A based systematic P1 modifications alone or/and in combination with further P1; variations. These SAR efforts led to the discovery of a number of potent and selective HCV NS3 protease inhibitors such as 4B, 9, and 12 endowed with impressive cellular activity as measured in the replicon assay and very good therapeutic indexes. On the basis of its overall profile, compound 4B (VX-950) has been selected for human clinical trials.
Keywords: hcv infection, ns3 protease, enzyme inhibition, replicon assay, cytotoxicity, alpha-ketoamide
Letters in Drug Design & Discovery
Title: P1 and P1; Optimization of [3,4]-Bicycloproline P2 Incorporated Tetrapeptidyl α-Ketoamide Based HCV Protease Inhibitors
Volume: 2 Issue: 2
Author(s): Shu-Hui Chen, Jason Lamar, Yvonne Yip, Frantz Victor, Robert B. Johnson, Q. May Wang, John I. Glass, Beverly Heinz, Joseph Colacino, Deqi Guo, Mark Tebbe and John E. Munroe
Affiliation:
Keywords: hcv infection, ns3 protease, enzyme inhibition, replicon assay, cytotoxicity, alpha-ketoamide
Abstract: We describe herein tetrapeptidyl α-ketoamide 4A based systematic P1 modifications alone or/and in combination with further P1; variations. These SAR efforts led to the discovery of a number of potent and selective HCV NS3 protease inhibitors such as 4B, 9, and 12 endowed with impressive cellular activity as measured in the replicon assay and very good therapeutic indexes. On the basis of its overall profile, compound 4B (VX-950) has been selected for human clinical trials.
Export Options
About this article
Cite this article as:
Chen Shu-Hui, Lamar Jason, Yip Yvonne, Victor Frantz, Johnson B. Robert, Wang May Q., Glass I. John, Heinz Beverly, Colacino Joseph, Guo Deqi, Tebbe Mark and Munroe E. John, P1 and P1; Optimization of [3,4]-Bicycloproline P2 Incorporated Tetrapeptidyl α-Ketoamide Based HCV Protease Inhibitors, Letters in Drug Design & Discovery 2005; 2 (2) . https://dx.doi.org/10.2174/1570180053175115
DOI https://dx.doi.org/10.2174/1570180053175115 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Effects of Hyperlipidemia and Cardiovascular Diseases on Proliferation, Differentiation and Homing of Mesenchymal Stem Cells
Current Stem Cell Research & Therapy Mechanisms of Plant Defense Under Pathogen Stress: A Review
Current Protein & Peptide Science Epidemiology, Evolution, Transmission, and Therapeutics of COVID-19 Outbreak: An Update on the Status
Coronaviruses The Antimitotic Potential of PARP Inhibitors, An Unexplored Therapeutic Alternative
Current Topics in Medicinal Chemistry Chemogenomics Approaches for Receptor Deorphanization and Extensions of the Chemogenomics Concept to Phenotypic Space
Current Topics in Medicinal Chemistry Attacking the SARS-CoV-2 Replication Machinery with the Pathogen Box’s Molecules
Letters in Drug Design & Discovery Novel Hybrid Molecules of Quinazoline Chalcone Derivatives: Synthesis and Study of in vitro Cytotoxic Activities
Letters in Drug Design & Discovery Antidiabetic Drugs and their Potential Use in COVID-19: A Mechanistic Approach
Endocrine, Metabolic & Immune Disorders - Drug Targets 3D-QSAR Studies of Natural Steroidal Saponins as Anticancer Agents in Human Nasopharyngeal Carcinoma Epithelial Cells
Letters in Drug Design & Discovery Structure-Activity Relationships of Pyrrole Hydrazones as New Anti-Tuberculosis Agents
Medicinal Chemistry Recent Advancement of Pyrazole Scaffold Based Neuroprotective Agents: A Review
CNS & Neurological Disorders - Drug Targets Phosphodiesterase 5 Inhibitors - Drug Design and Differentiation Based on Selectivity, Pharmacokinetic and Efficacy Profiles
Current Pharmaceutical Design Glycogen Phosphorylase Inhibitors
Mini-Reviews in Medicinal Chemistry 3D-QSAR Studies on Plasmodium falciparam Proteins: A Mini-Review
Combinatorial Chemistry & High Throughput Screening Iron Oxide Nanoparticle Platform for Biomedical Applications
Current Medicinal Chemistry Potential and Perspectives of Cyclonucleosides
Current Medicinal Chemistry Herbal Medicines as Potential Inhibitors of SARS-CoV-2 Infection
Current Pharmaceutical Design Orphan Nuclear Receptor Modulators
Current Topics in Medicinal Chemistry Variation of pKa in the N-Terminal Tyrosine Side Chain in Octapeptide Analogs of Tendamistat Influences α-Amylase Inhibition
Protein & Peptide Letters Effects of Drug Transporters on Pharmacological Responses and Safety
Current Drug Metabolism