Combinatorial Chemistry and Molecular Diversity in Drug Discovery

by Gordon, Eric M.; Kerwin, James F.

• ISBN13: 9780471155188
• ISBN10: 0471155187
• Edition: 1st
• Format: Hardcover
• Copyright: 1998-08-27
• Publisher: Wiley-Liss

Summary

Combinatorial Chemistry and Molecular Diversity in Drug Discovery is one of the first comprehensive books to cover this explosive area. It is must reading for medicinal chemists, pharmacologists, molecular biologists, biochemists, enzymologists, and drug discovery research managers in industry, academia, and government.

Author Biography

Eric M. Gordon and James F. Kerwin are the authors of Combinatorial Chemistry and Molecular Diversity in Drug Discovery, published by Wiley.

Table of Contents

Foreword: Combinatorial Chemistry at a Crossroads	ix	(8)
Walter H. Moos, MitoKor, San Diego, California
Preface	xvii	(4)
Contributors	xxi
PART I. Combinatorial Chemistry and Molecular Diversity: An Introduction	1	(178)
1. Historical Overview of the Developing Field of Molecular Diversity	3	(14)
John C. Chabala, Pharmacopeia Inc., Princeton, New Jersey
2. Strategies in the Design and Synthesis of Chemical Libraries	17	(22)
Eric M. Gordon, Versicor, Inc., Fremont, California
3. Solid-Phase Peptide Synthesis, Lead Generation, and Optimization	39	(72)
Bruce Seligman, SIDDCO, Tucson, Arizona
Michael Lebl, Trega Biosciences, San Diego, California
Kit S. Lam, Arizona Cancer Center, Tucson, Arizona
4. Light-Directed Chemical Synthesis of Positionally Encoded Peptide Arrays	111	(22)
Jeffrey W. Jacobs
Dinesh V. Patel
Zhengyu Yuan, Versicor, Inc., Fremont, California
Christopher P. Holmes
John Schullek, Affymax Research Institute, Palo Alto, California
Valery V. Antonenko
J. Russell Grove
Vicolay Kulikov
Derek Maclean
Marc Navre
Cindy Nguyen
Lihong Shi
Arathi Sundaram
Steven A. Sundberg, Affymax Research Institute, Santa Clara, California
5. Conformationally Restricted Peptide and Peptidomimetic Libraries	133	(18)
Alex A. Virgilio
Jonathan A. Ellman, Department of Chemistry, University of California at Berkeley, Berkeley, California
6. Submonomer Approaches for the Generation of Molecular Diversity: Nonnatural Oligomer and Organic Template Libraries	151	(14)
Lutz S. Richter
Dane A. Goff
Kerry L. Spear
Eric J. Martin
Ronald N. Zuckermann, Chiron Corporation, Emeryville, California
7. Oligonucleotide Libraries as a Source of Molecular Diversity	165	(14)
Houng-Yau Mei, Parke - Davis Pharmaceutical Research, Division of Warner - Lambert Company, Ann Arbor, Michigan
Anthony Czarnik, IRORI, La Jolla, California
PART II. Small Molecule Libraries	179	(158)
8. Small Molecule Libraries: Overview of Issues and Strategies in Library Design	181	(8)
John J. Baldwin, Pharmacopeia, Inc., Princeton, New Jersey
9. Protease Inhibitor Libraries	189	(12)
Dinesh V. Patel, Versicor, Inc., Fremont, California
David A. Campbell, Affymax Research Institute, Santa Clara, California
10. Heterocyclic Combinatorial Chemistry: Azine and Diazepine Pharmacophores	201	(12)
Mikhail F. Gordeev
Dinesh V. Patel, Versicor, Inc., Fremont, California
11. Scaffolds for Small Molecule Libraries	213	(14)
Michael R. Pavia, Millenium Pharmaceuticals Inc., Cambridge, Massachusetts
12. Application of Combinatorial Chemistry to Biopolymers	227	(16)
Edmund J. Moran, Ontogen Corp., Carlsbad, California
13. Oligosaccharide and Glycoconjugate Solid-Phase Synthesis Technologies for Drug Discovery	243	(28)
Michael J. Sofia, Transcell Technologies, Inc., Cranbury, New Jersey
14. Encoded Combinatorial Chemistry	271	(20)
Jeffrey W. Jacobs
Zhi-Jie Ni, Versicor, Inc., Fremont, California
15. Parallel Organic Synthesis in Array Format	291	(16)
Steven E. Hall, Sphinx Pharmaceuticals, A Division of Eli Lilly & Co., Durham, North Carolina
16. Synthetic Organic Chemistry on Solid Support	307	(30)
Stephen W. Kaldor
Miles G. Siegel, Lilly Research Laboratories, A Division of Eli Lilly & Company, Indianapolis, Indiana
PART III. Automation, Analytical, and Computational Methods	337	(50)
17. Automation of Combinatorial Chemistry for Large Libraries	339	(10)
Michael Needels
Jeffrey Sugarman, Affymax Research Institute, Palo Alto, California
18. Analytical Chemistry Issues in Combinatorial Organic Synthesis	349	(20)
William L. Fitch
Gary C. Look
George Detre, Affymax Research Institute, Santa Clara, California
19. Quantifying Diversity	369	(18)
Yvonne C. Martin
Robert D. Brown
Mark G. Bures, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois
PART IV. Biological Diversity	387	(32)
20. Protein Scaffolds for Peptide Libraries	389	(12)
Ronald H. Hoess, Dupont-Merck Pharmaceutical Company, Wilmington, Delaware
21. Combinatorial Biosynthesis of "Unnatural" Natural Products	401	(18)
Chaitan Khosla, Departments of Chemistry and Chemical Engineering, Stanford University, Stanford, California
PART V. Screening	419	(26)
22. Strategies for Screening Combinatorial Libraries	421	(12)
Bruce A. Beutel, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois
23. Approaches and Technologies for Screening Large Combinatorial Libraries	433	(12)
Nolan H. Sigal
Daniel Chelsky, Pharmacopeia, Inc., Princeton, New Jersey
PART VI. Combinatorial Drug Screening and Development	445	(54)
24. Combinatorial Drug Discovery: Concepts	447	(6)
Judd Berman, Glaxo Wellcome Research Institute, Research Triangle Park, North Carolina
Russell J. Howard, Affymax Research Institute, Santa Clara, California
25. ADME/PK Assays in Screening for Orally Active Drug Candidates	453	(22)
Jacqueline A. Gibbons
Eric W. Taylor
Rene A. Braeckman, Chiron Corporation, Emeryville, California
26. Combinatorial Technologies: Prospects and Future Issues	475	(8)
James F. Kerwin, Jr., Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois
27. Appendix: Combinatorial Chemistry Information Management	483	(16)
David Weininger, Daylight Chemical Information Systems, Inc., Santa Fe, New Mexico
Index	499