Antiviral Drugs. From Basic Discovery Through Clinical Trials

  • ID: 2171967
  • Book
  • 472 Pages
  • John Wiley and Sons Ltd
1 of 4

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

Note: Product cover images may vary from those shown
2 of 4
CONTRIBUTORS ix

PREFACE xiii

PART I HUMAN IMMUNODEFICIENCY VIRUS

Section I HIV Protease Inhibitors

1 Discovery and Development of Atazanavir 3Awny Farajallah, R. Todd Bunch, and Nicholas A. Meanwell

2 Discovery and Development of PL–100, A Novel HIV–1 Protease Inhibitor 19Jinzi J. Wu and Joseph Musto

3 Darunavir (Prezista, TMC114): From Bench to Clinic, Improving Treatment Options for HIV–Infected  Patients 31Marie–Pierre de Bethune, Vanitha Sekar, Sabrina Spinosa–Guzman, Marc Vanstockem, Sandra De Meyer, Piet Wigerinck, and Eric Lefebvre

4 Discovery and Development of Tipranavir 47Karen 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 59Jerome Guillemont, Katia Boven, Herta Crauwels, and Marie–Pierre de Bethune

6 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 B´ethune

Section III HIV Nucleoside Reverse Transcriptase Inhibitors

7 Discovery and Development of Tenofovir Disoproxil Fumarate 85Erik De Clercq

8 Discovery and Development of Apricitabine 103Susan 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 117Patrick Dorr and Paul Stupple

10 Discovery of the CCR5 Antagonist Vicriviroc (Sch 417690/Sch–D) for the Treatment of HIV–1 Infection 137Jayaram R. Tagat, Julie M. Strizki, and Lisa M. Dunkle

11 Discovery and Development of HIV–1 Entry Inhibitors That Target gp120 149John 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 163Melissa S. Egbertson, John S. Wai, Mark Cameron, and R. Scott Hoerrner

13 Discovery and Development of HIV Integrase Inhibitor Raltegravir 181Vincenzo Summa and Paola Pace

14 Elvitegravir: A Novel Monoketo Acid HIV–1 Integrase Strand Transfer Inhibitor 197Hisashi Shinkai, Masanori Sato, and Yuji Matsuzaki

PART II HEPATITIS C VIRUS

Section VI Protease Inhibitors

15 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. Kwong

16 Discovery and Development of BILN 2061 and Follow–up BI 201335 225Montse Llinas–Brunet and Peter W. White

17 Intervention of Hepatitis C Replication Through NS3–4A, the Protease Inhibitor Boceprevir 239Srikanth Venkatraman and F. George Njoroge

18 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. Buckman

19 Discovery and Development of the HCV Protease Inhibitor TMC435 273Pierre Raboisson, Gregory Fanning, Herman de Kock, Asa 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 287Klaus Klumpp and David B. Smith

21 Discovery and Development of PSI–6130/RG7128 305Phillip 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 317Kai Lin

23 HCV Viral Entry Inhibitors 329Flossie Wong–Staal, Guohong Liu, and Jeffrey McKelvy

PART III RESPIRATORY SYNCYTIAL VIRUS INHIBITORS

24 Discovery of the RSV Inhibitor TMC353121 341Jean–Francois Bonfanti, Gabriela Ispas, Frans Van Velsen, Wieslawa Olszewska, Tom Gevers, and Dirk Roymans

25 Discovery and Development of Orally Active RSV Fusion Inhibitors 353Nicholas A. Meanwell, Christopher W. Cianci, and Mark R. Krystal

26 Discovery and Development of RSV604 367Joanna Chapman and G. Stuart Cockerill

PART IV INFLUENZA, HEPATITIS B, AND CYTOMEGALOVIRUS INHIBITORS

27 Discovery and Development of Influenza Virus Sialidase Inhibitor Relenza 385Robin Thomson and Mark von Itzstein

28 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–Smith

29 Benzimidazole Ribonucleosides: Novel Drug Candidates for the Prevention and Treatment of Cytomegalovirus Diseases 417Karen K. Biron, Kristjan S. Gudmundsson, and John C. Drach

INDEX 435

Note: Product cover images may vary from those shown
3 of 4

Loading
LOADING...

4 of 4
Wieslaw M. Kazmierski
Note: Product cover images may vary from those shown
5 of 4
Note: Product cover images may vary from those shown
Adroll
adroll