Medicinal Chemistry Reviews

Volume 50, Chapter 15
Sofosbuvir:  A Breakthrough Curative Therapy for the Treatment of HCV Infection
Michael J. Sofia

1.    Introduction                                                                                                                397

2.   The HCV NS5B RNA-Dependent RNA Viral Polymerase                                          399

3.   First-Generation HCV Nucleoside NS5B Inhibitors                                                   400

4.   Design of a Second-Generation HCV NS5B Nucleotide Inhibitor                           402

5.   Medicinal Chemistry and Clinical Candidate Selection                                          405

6.   Prodrug Metabolism and Liver Targeting                                                                 408

7.   PSI-7851 Clinical Proof-of-Concept Study                                                                 409

8.   Preparation of the Single Diastereomer PSI-7977 (Sofosbuvir)                             410

9.   Sofosbuvir Preclinical Assessment                                                                            411

10. Sofosbuvir Clinical Studies                                                                                         412

11. Sofosbuvir and Viral Resistance                                                                                414

12. Conclusion                                                                                                                   415

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