Antiviral Drugs

Wieslaw M. Kazmierski, PhD, has worked on novel HIV and HCV therapies in both small and large pharma settings in the last two decades, helping to advance molecules to clinical trials. Dr. Kazmierski has authored numerous peer reviewed publications and has been named a co-inventor on many patents. He has edited scientific books and had served on journal editorial boards.

"I very much enjoyed this book and learned greatly from it ... The book is a valuable resource for researchers working in the discovery and early development of antiviral agents, and also for those simply interested in this area." (ChemMedChem, 1 January 2012)

• Contributors ixPreface xiiiPart I Human Immunodeficiency Virus Section I HIV Protease Inhibitors1 Discovery and Development of Atazanavir 3Awny Farajallah, R. Todd Bunch, and Nicholas A. Meanwell2 Discovery and Development of PL-100, A Novel HIV-1 Protease Inhibitor 19Jinzi J. Wu and Joseph Musto3 Darunavir (Prezista, TMC114): From Bench to Clinic, Improving Treatment Options for HIV-InfectedPatients 31Marie-Pierre de Béthune, Vanitha Sekar, Sabrina Spinosa-Guzman, Marc Vanstockem, Sandra De Meyer, Piet Wigerinck, and Eric Lefebvre4 Discovery and Development of Tipranavir 47Karen R. RominesSection II HIV Non-nucleoside Reverse Transcriptase Inhibitors5 TMC278 (Rilpivirine): A Next-Generation NNRTI in Phase III Clinical Development for Treatment-Naive Patients 59Jérôme Guillemont, Katia Boven, Herta Crauwels, and Marie-Pierre de Béthune6 Etravirine: From TMC125 to Intelence: A Treatment Paradigm Shift for HIV-Infected Patients 71Koen Andries, Ann Debunne, Thomas N. Kakuda, Michael Kukla, Ruud Leemans, Johan Vingerhoets, Brian Woodfall, and Marie-Pierre de BéthuneSection III HIV Nucleoside Reverse Transcriptase Inhibitors7 Discovery and Development of Tenofovir Disoproxil Fumarate 85Erik De Clercq8 Discovery and Development of Apricitabine 103Susan Cox, John Deadman, Justine Southby, and Jonathan CoatesSection IV HIV Entry Inhibitors9 Discovery and Development of Maraviroc and PF-232798: CCR 5 Antagonists for the Treatment of HIV-1 Infection 117Patrick Dorr and Paul Stupple10 Discovery of the CCR5 Antagonist Vicriviroc (Sch 417690/Sch-D) for the Treatment of HIV-1Infection 137Jayaram R. Tagat, Julie M. Strizki, and Lisa M. Dunkle11 Discovery and Development of HIV-1 Entry Inhibitors That Target gp 120 149John F. Kadow, John Bender, Alicia Regueiro-Ren, Yasutsugu Ueda, Tao Wang, Kap-Sun Yeung, and Nicholas A. MeanwellSection V HIV Integrase Inhibitors12 Discovery of MK-0536: A Potential Second-Generation HIV-1 Integrase Strand Transfer Inhibitorwith a High Genetic Barrier to Mutation 163Melissa S. Egbertson, John S. Wai, Mark Cameron, and R. Scott Hoerrner13 Discovery and Development of HIV Integrase Inhibitor Raltegravir 181Vincenzo Summa and Paola Pace14 Elvitegravir: A Novel Monoketo Acid HIV-1 Integrase Strand Transfer Inhibitor 197Hisashi Shinkai, Masanori Sato, and Yuji MatsuzakiPart II Hepatitis C VirusSection VI Protease Inhibitors15 Discovery and Development of Telaprevir 209Anne-Laure Grillot, Luc J. Farmer, B. Govinda Rao, William P. Taylor, Ilan S. Weisberg, Ira M. Jacobson, Robert B. Perni, and Ann D. Kwong16 Discovery and Development of BILN 2061 and Follow-up BI 201335 225Montse Llinàs-Brunet and Peter W. White17 Intervention of Hepatitis C Replication Through NS3-4A, the Protease Inhibitor Boceprevir 239Srikanth Venkatraman and F. George Njoroge18 Discovery and Development of the HCV NS3/4A Protease Inhibitor Danoprevir (ITMN-191/RG7227)257Scott D. Seiwert, Karl Kossen, Lin Pan, Jyanwei Liu, and Brad O. Buckman19 Discovery and Development of the HCV Protease Inhibitor TMC 435 273Pierre Raboisson, Gregory Fanning, Herman de Kock, Åsa Rosenquist, René Verloes, and Kenneth SimmenSection VII HCV Polymerase Nucleoside Inhibitors20 Discovery and Clinical Evaluation of the Nucleoside Analog Balapiravir (R1626) for the Treatment ofHCV Infection 287Klaus Klumpp and David B. Smith21 Discovery and Development of PSI-6130/RG 7128 305Phillip A. Furman, Michael J. Otto, and Michael J. SofiaSection VIII Other HCV Inhibitors22 Discovery of Cyclophilin Inhibitor NIM811 as a Novel Therapeutic Agent for HCV 317Kai Lin23 HCV Viral Entry Inhibitors 329Flossie Wong-Staal, Guohong Liu, and Jeffrey McKelvyPart III Respiratory Syncytial Virus Inhibitors24 Discovery of the RSV Inhibitor TMC 353121 341Jean-François Bonfanti, Gabriela Ispas, Frans Van Velsen, Wieslawa Olszewska, Tom Gevers, and Dirk Roymans25 Discovery and Development of Orally Active RSV Fusion Inhibitors 353Nicholas A. Meanwell, Christopher W. Cianci, and Mark R. Krystal26 Discovery and Development of RSV 604 367Joanna Chapman and G. Stuart CockerillPart IV Influenza, Hepatitis B, and Cytomegalovirus Inhibitors27 Discovery and Development of Influenza Virus Sialidase Inhibitor Relenza 385Robin Thomson and Mark von Itzstein28 Discovery and Development of Entecavir 401Richard Wilber, Bruce Kreter, Marc Bifano, Stephanie Danetz, Lois Lehman-McKeeman, Daniel J. Tenney, Nicholas Meanwell, Robert Zahler, and Helena Brett-Smith29 Benzimidazole Ribonucleosides: Novel Drug Candidates for the Prevention and Treatment ofCytomegalovirus Diseases 417Karen K. Biron, Kristjan S. Gudmundsson, and John C. DrachIndex 435