Antiviral Drugs: From Basic Discovery Through Clinical Trials

A complete, one–stop reference to real–world antiviral drug discovery and development
The field of antiviral drugs continues to evolve at a fast pace in response to new virus discoveries and development of viral resistance to existing therapies. This book provides case histories and arms both basic and industrial pharmaceutical researchers with practical tools to tackle the ongoing challenges of antiviral drug design, discovery, and development.
Written by leading authorities from academia and industry, Antiviral Drugs compiles information previously scattered across the literature into one complete, self–contained volume, unlike any other book on the subject. The authors draw on their own extensive research experience to present numerous case studies illustrating the full drug design process, from bench to clinic, with special emphasis on proven strategies for the development of drugs against all major viral infectious diseases, including HIV, HCV, RSV, influenza, HBV, and CMV.
Readers will find everything they need to analyze, understand, and apply discovery and development principles, including:
Coverage of newly approved antiviral drugs and compounds in clinical development
Emphasis on novel experimental molecules used to combat viral infections
Viral inhibitory mechanistic information
Clear examples for how to bring drugs from laboratory discovery to clinical trials
Effective examples and strategies of lead optimization yielding molecules of clinical value
Practical solutions for issues such as pharmacokinetics, viral resistance, and more
Key and specific references for readers wishing to explore the topics further

Spis treści:
CONTRIBUTORS ix
PREFACE xiii
PART I HUMAN IMMUNODEFICIENCY VIRUS
Section I HIV Protease Inhibitors
1 Discovery and Development of Atazanavir 3
Awny Farajallah, R. Todd Bunch, and Nicholas A. Meanwell
2 Discovery and Development of PL–100, A Novel HIV–1 Protease Inhibitor 19
Jinzi J. Wu and Joseph Musto
3 Darunavir (Prezista, TMC114): From Bench to Clinic, Improving Treatment Options for HIV–Infected  Patients 31
Marie–Pierre de B´ethune, Vanitha Sekar, Sabrina Spinosa–Guzman, Marc Vanstockem, Sandra De Meyer, Piet Wigerinck, and Eric Lefebvre
4 Discovery and Development of Tipranavir 47
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–Naive Patients 59
J´erˆome Guillemont, Katia Boven, Herta Crauwels, and Marie–Pierre de B´ethune
6 Etravirine: From TMC125 to Intelence: A Treatment Paradigm Shift for HIV–Infected Patients 71
Koen Andries, Ann Debunne, Thomas N. Kakuda, Michael Kukla, Ruud Leemans, Johan Vingerhoets, Brian Woodfall, and Marie–Pierre de B´ethune
Section III HIV Nucleoside Reverse Transcriptase Inhibitors
7 Discovery and Development of Tenofovir Disoproxil Fumarate 85
Erik De Clercq
8 Discovery and Development of Apricitabine 103
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 117
Patrick Dorr and Paul Stupple
10 Discovery of the CCR5 Antagonist Vicriviroc (Sch 417690/Sch–D) for the Treatment of HIV–1 Infection 137
Jayaram R. Tagat, Julie M. Strizki, and Lisa M. Dunkle
11 Discovery and Development of HIV–1 Entry Inhibitors That Target gp120 149
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 163
Melissa S. Egbertson, John S. Wai, Mark Cameron, and R. Scott Hoerrner
13 Discovery and Development of HIV Integrase Inhibitor Raltegravir 181
Vincenzo Summa and Paola Pace
14 Elvitegravir: A Novel Monoketo Acid HIV–1 Integrase Strand Transfer Inhibitor 197
Hisashi Shinkai, Masanori Sato, and Yuji Matsuzaki
PART II HEPATITIS C VIRUS
Section VI Protease Inhibitors
15 Discovery and Development of Telaprevir 209
Anne–Laure Grillot, Luc J. Farmer, B. Govinda Rao, William P. Taylor, Ilan S. Weisberg, Ira M. Jacobson, Robert B. Perni, and Ann D. Kwong
16 Discovery and Development of BILN 2061 and Follow–up BI 201335 225
Montse Llin`as–Brunet and Peter W. White
17 Intervention of Hepatitis C Replication Through
NS3–4A, the Protease Inhibitor Boceprevir 239
Srikanth Venkatraman and F. George Njoroge
18 Discovery and Development of the HCV NS3/4A Protease
Inhibitor Danoprevir (ITMN–191/RG7227) 257
Scott D. Seiwert, Karl Kossen, Lin Pan, Jyanwei Liu, and Brad O. Buckman
19 Discovery and Development of the HCV Protease Inhibitor TMC435 273
Pierre Raboisson, Gregory Fanning, Herman de Kock, A°sa Rosenquist, Rene´ 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 287
Klaus Klumpp and David B. Smith
21 Discovery and Development of PSI–6130/RG7128 305
Phillip A. Furman, Michael J. Otto, and Michael J. Sofia
Section VIII Other HCV Inhibitors
22 Discovery of Cyclophilin Inhibitor NIM811 as a Novel Therapeutic Agent for HCV 317
Kai Lin
23 HCV Viral Entry Inhibitors 329
Flossie Wong–Staal, Guohong Liu, and Jeffrey McKelvy
PART III RESPIRATORY SYNCYTIAL VIRUS INHIBITORS
24 Discovery of the RSV Inhibitor TMC353121 341
Jean–Franc¸ois Bonfanti, Gabriela Ispas, Frans Van Velsen, Wieslawa Olszewska, Tom Gevers, and Dirk Roymans
25 Discovery and Development of Orally Active RSV Fusion Inhibitors 353
Nicholas A. Meanwell, Christopher W. Cianci, and Mark R. Krystal
26 Discovery and Development of RSV604 367
Joanna Chapman and G. Stuart Cockerill
PART IV INFLUENZA, HEPATITIS B, AND CYTOMEGALOVIRUS INHIBITORS
27 Discovery and Development of Influenza Virus Sialidase Inhibitor Relenza 385
Robin Thomson and Mark von Itzstein
28 Discovery and Development of Entecavir 401
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 417
Karen K. Biron, Kristjan S. Gudmundsson, and John C. Drach
INDEX 435

Nota biograficzna:
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.

Okładka tylna:

A complete, one–stop reference to real–world antiviral drug discovery and development
The field of antiviral drugs continues to evolve at a fast pace in response to new virus discoveries and development of viral resistance to existing therapies. This book provides case histories and arms both basic and industrial pharmaceutical researchers with practical tools to tackle the ongoing challenges of antiviral drug design, discovery, and development.
Written by leading authorities from academia and industry, Antiviral Drugs compiles information previously scattered across the literature into one complete, self–contained volume, unlike any other book on the subject. The authors draw on their own extensive research experience to present numerous case studies illustrating the full drug design process, from bench to clinic, with special emphasis on proven strategies for the development of drugs against all major viral infectious diseases, including HIV, HCV, RSV, influenza, HBV, and CMV.
Readers will find everything they need to analyze, understand, and apply discovery and development principles, including:
Coverage of newly approved antiviral drugs and compounds in clinical development
Emphasis on novel experimental molecules used to combat viral infections
Viral inhibitory mechanistic information
Clear examples for how to bring drugs from laboratory discovery to clinical trials
Effective examples and strategies of lead optimization yielding molecules of clinical value
Practical solutions for issues such as pharmacokinetics, viral resistance, and more
Key and specific references for readers wishing to explore the topics further