Antiviral Drugs: From Basic Discovery Through Clinical Trials / Edition 1

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Overview

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.

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Editorial Reviews

From the Publisher
"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)
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Product Details

  • ISBN-13: 9780470455630
  • Publisher: Wiley
  • Publication date: 8/23/2011
  • Edition number: 1
  • Pages: 480
  • Product dimensions: 8.70 (w) x 11.00 (h) x 1.20 (d)

Meet the Author

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.

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Table of Contents

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 Bethune, 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
Jerome Guillemont, Katia Boven, Herta Crauwels, and Marie-Pierre de Bethune

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 Báethune

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 Llinas-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, 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 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-Francois 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

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