Antiviral Drugs - From Basic Discov. Through Clin. Trials - W. Kazmierski (Wiley, 2011) WW

468 Pages·2011·18.8 MB·English

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ANTIVIRAL DRUGS

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ANTIVIRAL DRUGS

From Basic Discovery Through Clinical Trials

Edited by

WIESLAW M. KAZMIERSKI, Ph.D.

A JOHN WILEY & SONS, INC., PUBLICATION

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Copyright C⃝ 2011 by John Wiley & Sons, Inc. All rights reserved.

Published by John Wiley & Sons, Inc., Hoboken, New Jersey.
Published simultaneously in Canada.

No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying,
recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written
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ttp://www.wiley.com/go/permission.

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Library of Congress Cataloging-in-Publication Data:

Antiviral drugs: from basic discovery through clinical trials / edited by Wieslaw M. Kazmierski.

p. ; cm.

Includes bibliographical references and index.
ISBN 978-0-470-45563-0 (cloth)
1. Antiviral agents.
I. Kazmierski, Wieslaw M.

[DNLM: 1. Antiviral Agents–therapeutic use.
2. Clinical Trials as Topic.
3. Drug Discovery.

4. Drug Evaluation.
QV 268.5 A63347 2011]

RM411.A5753 2011
615′.7924–dc22

2010025372

Printed in Singapore

oBook ISBN: 9780470929353
ePDF ISBN: 9780470929346
ePub ISBN: 9780470934685

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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 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

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CONTENTS

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

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CONTENTS
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19
Discovery and Development of the HCV Protease Inhibitor TMC435
273

Pierre Raboisson, Gregory Fanning, Herman de Kock, ˚Asa Rosenquist, Ren´e 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
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CONTRIBUTORS

Koen Andries, Johnson & Johnson Pharmaceutical Re-

search and Development, Beerse, Belgium

John Bender, Bristol-Myers Squibb Company Research

and Development, Wallingford, Connecticut

Marc Bifano, Bristol-Myers Squibb Company Research

and Development, Wallingford, Connecticut

Karen K. Biron, Pathfinder Pharmaceuticals, Inc., Durham,

North Carolina

Jean-Franc¸ois Bonfanti, Janssen R&D, Janssen-Cilag,

Johnson & Johnson, Val de Reuil, France

Katia Boven, Tibotec, Inc., Titusville, New Jersey

Helena Brett-Smith, Bristol-Myers Squibb Company Re-

search and Development, Wallingford, Connecticut

Brad O. Buckman, InterMune, Inc., Brisbane, California

R.
Todd
Bunch, Bristol-Myers
Squibb
Company,

Evansville, Indiana

Mark Cameron, Merck Research Laboratories, West Point,

Pennsylvania

Joanna Chapman, Arrow Therapeutics, Ltd., London, UK

Christopher W. Cianci, Bristol-Myers Squibb Company

Research and Development, Wallingford, Connecticut

Jonathan Coates, Avexa Ltd., Richmond, Victoria, Aus-

tralia

G. Stuart Cockerill, Arrow Therapeutics, Ltd., London,

UK

Susan Cox, Avexa Ltd., Richmond, Victoria, Australia

Herta Crauwels, Tibotec BVBA, Beerse, Belgium

Stephanie Danetz, Bristol-Myers Squibb Company Re-

search and Development, Wallingford, Connecticut

John Deadman, Avexa Ltd., Richmond, Victoria, Australia

Marie-Pierre de B´ethune, Tibotec BVBA, Beerse, Bel-

gium

Ann Debunne, Johnson & Johnson Pharmaceutical Re-

search and Development, Beerse, Belgium

Erik De Clercq, Rega Institute for Medical Research,

Leuven, Belgium

Herman de Kock, Tibotec BVBA, Beerse, Belgium

Sandra De Meyer, Tibotec BVBA, Beerse, Belgium

Patrick Dorr, Abbott Laboratories, Berkshire, UK

John C. Drach, School of Dentistry, University of Michi-

gan, Ann Arbor, Michigan

Lisa
M.
Dunkle, Merck
Research
Laboratories,

Kenilworth, New Jersey

Melissa S. Egbertson, Merck Research Laboratories, West

Point, Pennsylvania

Gregory Fanning, Tibotec BVBA, Beerse, Belgium

Awny Farajallah, Bristol-Myers Squibb Company, Plains-

boro, New Jersey

Luc J. Farmer, Vertex Pharmaceuticals, Inc., Cambridge,

Massachusetts

Phillip A. Furman, Pharmasset, Inc., Princeton, New

Jersey

Tom Gevers, Tibotec BVBA, Beerse, Belgium

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