This book focuses on new small molecule approaches to combat viral infections. The chapters describe the discovery and development from bench through the clinic of relatively recently-approved antiviral drugs and compounds in advanced clinical development. Organized by a virus (such as HIV, HCV, RSV, influenza, HBV and CMV) and written by top academic and industrial authorities in the field, the book provides a unique opportunity to study, understand and apply discovery and development principles and learning without the need for an individual to research, analyze and synthesize all immense sourcing references. Topics showcase challenges and solutions of issues encountered, offering tremendous experience accumulated over many years of research that will be particularly useful to basic and bench scientists as well as clinicians as they continue discovering and developing new drugs and therapies.

Part I. Human Immunodeficiency Virus (HIV).
Section I. HIV Protease Inhibitors.

1. Atazanavir (Nicholas A. Meanwell, R. Todd Bunch and Awny Farajallah).

2. PL–100: A Novel HIV–1 Protease Inhibitor (Jinzi J. Wu and Joseph Musto).

3. Darunavir (PREZISTA, TMC114): from bench to clinic, improving treatment options for HIV–infected patients (Marie–Pierre de Béthune, Vanitha Sekar, Sabrina Spinosa–Guzman, Marc Vanstockem, Sandra De Meyer, Piet Wigerinci ad Eric Lefebvre).

4. Discovery and Development o Tipranavir (Karen R. Romines).

Section II. HIV Non–Nucleoside Reverse Transcriptase Inhibitors.

5. TMC278 (rilpivirine): a next–generation NNRTI in Phase III clinical development for treatment–naïve patients (Jérôme Guillemont, Herta Crauwels, Katia Boven and Marie–Pierre de Béthune).

6. Etravirine: from TMC125 to INTELENCE – a treatment paradigm shift for HIV–infected patients (Koen Andries, Ann Debunne, Thomas N. Kakuda, Michael Kukla, Ruud Leemans, Johan Vingerhoets, Brian Woodfall and Marie–Pierre de Béthune).

Section III. Nucleoside Reverse Transcriptase Inhibitors.

7. Tenofovir Disoproxil Fumarate (Tdf): Discovery and Clinical Development (Erik De Clercq).

8. Discovery and Clinical Development of Apricitabine (Susan Cox, John Deadman, Justine Southby and Jonathan Coates).

Section IV. HIV Entry Inhibitors.

9. Discovery and Development of Maraviroc and PF–232798: CCR5 Antagonists for the treatment of HIV–1 infection (Patrick Dorr and Paul Stupple).

10. Discovering of the CCR5 Antagonist Vicriviroc (SCH 417690/SCH–D) For Treatment of HIV–1 Infection (Jayaram R. Tagat, Julie M. Strizki, and Lisa M. Dunkle).

11. Discovery and Development of HIV–1 Entry Inhibitors That Target gp120 (John F. Kadow, John Bender, Alicia Regueiro–Ren, Yasutsugu Ueda, Tao Wang, Kap–Sun Yeung and Nicholas A. Meanwell).

Section V. HIV Integrase Inhibitors.

12. Discovery of MK–0536: A Potential Second Generation HIV–1 Integrase Strand Transfer Inhibitor with a High Genetic Barrier to Mutation (Melissa S. Egbertson, John S. Wai, Mark Cameron and R. Scott Hoerrner).

13. Discovery and Development of HIV Integrase Inhibitor Realegravir (Vincenzo Summa and Paola Pace).

14. Elvitegravir, A Novel Mono keto Acid HIV–1 Integrase Strand Transfer Inhibitor (Hisashi Shinkai, Masanori Sato and Yuji Matsuzaki).

Part II. Hepatitis C Virus (HCV).

Section VI. HCV Protease Inhibitors.

15. Telaprevir (Anne–Laure Grillot, Luc J. Farmer, B. Govinda Rao, William P. Taylor, Iian S. Weisberg, Ira M. Jacobson, Robert B. Perni and Ann D. Kwong).

16. Discovery and Development of BILN 2061 and Follow–up Bl 201335 (Montse–Llinàs–Brunet and Peter W. White).

17. Intervention of Hepatitis C Replication through NS3–4A Protease Inhibitor, Boceprevir (Srikanth Venkatraman and F. George Njoroge).

18. Discovery & Development of ITMN 191 (R7227) (Scott D. Seiwert, Karl Kossen, Lin Pan, Jyanwei Liu, and Brad O. Buckman).

19. Discovery and Development of the HCV Protease Inhibitor TMC435 (Pierre Raboisson, Gregory Fanning, Herman e Kork, Åsa Rosequist, René Verloes, and Kenneth Simmen).

Section VII. HCV Polymerase Nucleoside Inhibitors.

20. Discovery and clinical evaluation of the nucleoside analog Balapiravir (R1626) for the treatment of HCV infection (Klaus Klumpp and David S. Smith).

21. Discovery and Development of PSI–6130 / RG7128 (Phillip A. Furman, Michael J. Otto, and Michael J. Sofia).

Section VIII. Other HCV Inhibitors.

22. Discovering of cyclophilin inhibitor NIM811 as a novel therapeutic agent for HCV (Kai Lin).

23. HCV viral entry inhibitors (Flossie Wong–Staal, Guohong Liu and Jeffrey McKelvy).

Part III. Respiratory Syncytial Virus Inhibitors.

24. Discovery of the RSV inhibitor TMC353121 (Jean–François Bonfanti, Gabriela Ispas, Frans Van Velsen, Wieslawa Olszewska Tom Gevers and Dirk Roymans).

25. The discovery and development of orally active RSV fusion inhibitors (Nicholas A. Meanwell, Christopher W. Cianci and Mark R. Krystal).

26. Discovery and Development of RSV60449 (Joanna Chapman and G. Stuart Cockerill).

Part IV. Influenza, Hepatitis B and Cytomegalovirus Inhibitors.

27. Discovery and Development of Influenza Virus Sialidase Inhibitor Relenza (Robin Thomson and Mark von Itzstein).

28. Discovery and Development of Entecavir (Richard Wilber, Bruce Kreter, Marc Bifano, Stephanie Danetz, Lois Lehman–McKeeman, Daniel J. Tenney, Nicholas Meanwell, Robert Zahler and Helena Brett–Smith).

29. Benzimidazole ribonucleosides: Novel drug candidates for the prevention and treatment of cytomegalovirus diseases (Karen K. Biron, Kristjan S. Gudmundsson, and John C. Drach).