9780471398486

Drug Discovery and Development Vol. 1 : Drug Discovery

by
  • ISBN13:

    9780471398486

  • ISBN10:

    0471398489

  • Format: Hardcover
  • Copyright: 2006-06-16
  • Publisher: Wiley-Interscience

Note: Supplemental materials are not guaranteed with Rental or Used book purchases.

Purchase Benefits

  • Free Shipping On Orders Over $35!
    Your order must be $35 or more to qualify for free economy shipping. Bulk sales, PO's, Marketplace items, eBooks and apparel do not qualify for this offer.
  • Get Rewarded for Ordering Your Textbooks! Enroll Now
List Price: $160.00 Save up to $16.00
  • Rent Book $144.00
    Add to Cart Free Shipping

    TERM
    PRICE
    DUE

Supplemental Materials

What is included with this book?

  • The New copy of this book will include any supplemental materials advertised. Please check the title of the book to determine if it should include any access cards, study guides, lab manuals, CDs, etc.
  • The Rental copy of this book is not guaranteed to include any supplemental materials. Typically, only the book itself is included. This is true even if the title states it includes any access cards, study guides, lab manuals, CDs, etc.

Summary

This two volume set provides a comprehensive account of the entire sequence of operations involved in discovering a drug through the actual delivery of the drug to clinicians and medical practitioners. Includes case studies of the discovery of erythromycin analogs (antibiotics), Tagamet, and Ultiva (remifentanil) Discusses the discovery of agents for the treatment and management of bacterial infections, Parkinson's disease, psoriasis, ulcers and stomach pain, atopic dermatitis, asthma, and cancer Contains chapters on combinatorial chemistry, molecular biology-based drug discovery, genomics, and chemogenomics The first volume of this set thoroughly describes conceptualizing a drug, creating a library of candidates for testing, screening those candidates for in vitro and in vivo activity, conducting and analyzing the results of clinical trials, and revising the drug as necessary.

Author Biography

Mukund S. Chorghade, PHD, is President of Chorghade Enterprises, Inc., a firm based in Natick, Massachusetts that provides consultations to major pharmaceutical companieson collaborations with worldwide academic, government, and industrial laboratories; European technology-based companies; process reengineering; and project management of technology transfer.

Table of Contents

Contributors xiii
Preface xv
From Patent to Prescription: Paving the Perilous Path to Profit
1(16)
Richard J. Pariza
Introduction
1(2)
A Simple Solution to a Complex Problem
3(5)
An Intriguing Patent Problem
8(2)
Another Structural Insight
10(7)
References
15(2)
Medicinal Chemistry in the New Millennium: A Glance into the Future
17(86)
Paul W. Erhardt
Introduction
17(2)
Practice of Medicinal Chemistry
19(16)
Emergence as a Formalized Discipline
19(4)
Early Developments
23(3)
Present Status
26(1)
Examples Involving Site-Directed Mutagenesis
27(4)
Latest Trends
31(4)
Evolving Drug Discovery and Development Process
35(5)
Working Definition for Medicinal Chemistry
35(1)
Immediate- and Long-Term Roles for Medicinal Chemistry
36(4)
Pursuing Efficacy
40(6)
Gathering Positive, Neutral, and Negative SARs During HTS
41(1)
Example Involving Multidrug Resistance of Anticancer Agents
42(3)
Compound Libraries: Example of Working with Nature to Enhance Molecular Diversity
45(1)
Assessing and Handling Molecular Conformation
46(11)
Chemoinformatics
46(3)
Obtaining Chemically Correct 3D Structures
49(1)
Influence of Biological Environments: Example Involving Drug Metabolism
50(2)
Dynamic Energy Relationships: Example Involving a Small Ring System
52(2)
Druglike Properties and Privileged Structures
54(1)
Tiered Structural Information and Searching Paradigms
55(2)
ADMET Considerations
57(13)
Assuring Absorption
57(1)
Directing Distribution
58(1)
Herbal Remedies: Example of Working with Nature to Discover ADMET-Related Synergies
59(3)
Brute Force HTS to Uncover Multicomponent Synergies
62(1)
Controlling Metabolism: Example Involving a Soft Drug Strategy
63(2)
Optimizing Excretion
65(1)
Avoiding Toxicity
65(2)
Weighting Decision Criteria from Efficacy and ADMET SAR
67(3)
Process Chemistry Considerations
70(4)
Cost and Green Chemistry
70(1)
Defining Stereochemistry: Example Involving Benzylamine Chiral Auxiliary Synthetic Reagents
71(3)
Analytical Chemistry/X-ray Diffraction
74(4)
Latest Trends
74(1)
Examples Involving Dopamine Receptors, c-AMP Phosphodiesterase Enzymes, and the Dynamics of Protein Folding
75(3)
Summary
78(25)
General Points
78(3)
Attributes of Drug Discovery Libraries, Compound Hits, and Lead Compounds
81(1)
Formalized Instruction of Medicinal Chemistry
81(2)
Intellectual Property Considerations
83(1)
Knowledge Versus Diversity Paradox
84(1)
Acknowledgments
85(1)
References and Notes
85(18)
Contemporary Drug Discovery
103(26)
Lester A. Mitscher
Apurba Dutta
Introduction
103(1)
Getting Started
103(1)
Characteristics of a Suitable Lead Substance
104(4)
Potency and Selectivity
105(2)
Structure--Activity Relationships
107(1)
Toxicity
107(1)
Changing Appellation of the Best in Series: Analog Attrition
108(1)
Some Criteria That a Hit Must Satisfy to Become a Drug
108(8)
Level of Potency
109(1)
Comparison of Potency and Efficacy
110(1)
Druglike Character
110(1)
Efficacy Following Oral Administration
110(2)
Lipinski Rules for Oral Absorption
112(1)
Injectable Medications
113(1)
Distribution
113(1)
Serum Protein Binding
114(1)
Metabolism
114(1)
Distribution
114(1)
Excretion
115(1)
Patenting
115(1)
Pharmaceutical Properties
115(1)
Idiosyncratic Problems
115(1)
Summary
115(1)
Example of Drug Development That Illustrates Many of the Aforementioned Considerations
116(12)
Control of Blood Pressure with Drugs
116(1)
Historical Background
116(1)
Finding a Starting Point: A Clue from Nature
117(1)
Renin--Angiotensin--Aldosterone System
117(2)
Attempts to Inhibit Renin
119(1)
Attempts to Inhibit Angiotensin-Converting Enzyme
119(1)
Peptides Make Poor Orally Active Drugs
120(1)
Analoging Studies of Pit Viper--Inspired Peptides
120(1)
Peptidomimetics
120(1)
Adaptation to Inhibition of ACE
121(2)
Success Inspires Competition
123(1)
Taking a Different Approach
124(1)
Analoging to Enhance Absorption
124(2)
Clinical SAR
126(2)
More Recent Work
128(1)
Resume
128(1)
Conclusions
128(1)
Additional Reading
128(1)
Combinatorial Chemistry in the Drug Discovery Process
129(40)
Ian Hughes
Introduction
129(6)
The Birth of Combinatorial Chemistry
130(1)
Development of Screening Strategies for Libraries
131(1)
From Peptides to Small Molecule Synthesis
132(1)
Beyond Solid-Phase Chemistry
133(2)
The Role of Combinatorial Chemistry in Drug Discovery
135(2)
Designing Combinatorial Libraries
137(4)
Describing and Measuring Diversity
137(2)
A More Focused Approach
139(2)
Tools for Synthesis of Combinatorial Libraries
141(5)
Nonautomated Tools
141(2)
Mix-and-Sort Systems
143(1)
Automated Synthesizers
143(1)
Postsynthesis Processing
144(2)
Managing the Combinatorial Process
146(2)
Specification of Combinatorial Libraries
146(1)
Controlling the Automated Workflow
146(2)
From Specialist Discipline to Standard Tool
148(1)
Application of Combinatorial Chemistry in Drug Discovery
149(5)
Case History 1
150(1)
Case History 2
150(1)
Case History 3
151(1)
Case History 4
152(2)
The Future of Combinatorial Chemistry
154(1)
Dynamic Combinatorial Libraries
154(1)
Miniaturization
154(1)
Conclusions
155(14)
References
156(13)
Parallel Solution-Phase Synthesis
169(30)
Norton P. Peet
Hwa-Ok Kim
Introduction
169(1)
Ahead of Our Time
169(3)
Recent Reports of Parallel Solution-Phase Synthesis
172(6)
Solid Supported Reagents, Scavengers, and Catalysts
178(13)
The Future
191(8)
References
191(8)
Timing of Analog Research in Medicinal Chemistry
199(14)
Janos Fischer
Aniko Gere
Introduction
199(1)
Early Phase Analogs
199(3)
ACE Inhibitors
199(1)
AT1 Antagonists
200(1)
Proton Pump Inhibitors
200(1)
Insulin Sensitizers: Glitazones
200(2)
HMG-CoA Reductase Inhibitors
202(1)
Antimigraine Drugs
202(1)
Drug Analogs
202(6)
Metoclopramide Analogs
203(2)
Azatadine Analogs
205(1)
Miconazole Analogs
205(1)
Nifedipine Analogs
206(1)
Propranolol Analogs
207(1)
Clodronate Analogs
207(1)
Summary
208(5)
Acknowledgments
210(1)
References and Notes
210(3)
Possible Alternatives to High-Throughput Screening
213(20)
Camille G. Wermuth
Introduction
213(1)
Analog Design
214(3)
Definitions
214(1)
Pharmacophere-Based Analog Design: Scaffold Hopping or Scaffold Morphing
215(1)
Natural Compounds as Models
216(1)
Emergence of New Activities
216(1)
Physiopathological Hypotheses
217(4)
Discovery of Levodopa
217(2)
H2-Receptor Antagonists
219(1)
Rimonabant and Obesity
220(1)
Contributions from Clinical Investigations
221(2)
New Leads from Old Drugs: The SOSA Approach
223(5)
Rationale
223(1)
Examples
223(3)
Discussion
226(2)
Conclusion
228(5)
References
229(4)
Proteomics and Drug Discovery
233(40)
Susan Dana Jones
Peter G. Warren
Introduction
233(1)
Drug Discovery Process
234(2)
Process Overview
234(2)
Motivation for Improvement
236(1)
High-Throughput Screening Approaches to Drug Discovery
236(1)
Emerging Technologies and Approaches: Scale and Speed
237(1)
Genomics
237(1)
Proteomics
238(10)
Functional Areas of Proteomics
239(1)
Fractionation and Purification
239(1)
Identification
240(2)
Quantitation
242(1)
Characterization
243(5)
Protein Chip Technology
248(5)
Issues Addressed
248(1)
Current State of the Technology
249(4)
Proteomics Data Analysis: Computational Biology and Bioinformatics
253(3)
Proteomics and Drug Discovery
256(10)
Target Identification
256(2)
Target Validation
258(1)
Screening for Hits
259(2)
Lead Optimization
261(1)
Pharmacology and ADME-Tox
262(1)
Clinical Trials: Biomarkers and Pharmacogenomics
263(2)
Case Study
265(1)
Conclusions
266(7)
Acknowledgments
267(1)
References
267(2)
Appendix: Public-Domain Software Tools and Databases
269(4)
Using Drug Metabolism Databases During Drug Design and Development
273(22)
Paul W. Erhardt
Introduction
273(2)
Historical Perspective
275(1)
Present Status
276(4)
Future Prospects
280(7)
Summary
287(8)
References and Notes
288(7)
Discovery of the Antiulcer Drug Tagamet
295(18)
C. Robin Ganellin
Historical Background
295(3)
Prologue
295(1)
Pharmacological Receptors
296(1)
Peptic Ulcer Disease
296(2)
Search for New Antiulcer Drugs
298(1)
Search for an H2-Receptor Histamine Antagonist
298(7)
Histamine Receptors
298(1)
Biological Approach to a Histamine Antagonist at Non-H1 Receptors
299(1)
Chemical Approach to an Antagonist: Generating a Lead
300(1)
Lead Optimization
301(2)
Validating the Research Program
303(2)
Development of a Clinical Candidate Drug
305(4)
Dynamic Structure--Activity Analysis
305(1)
Imidazole Tautomerism and Sulfur Methylene Isosterism
306(1)
Isosteres of Thiourea and the Discovery of Cimetidine
307(1)
Cimetidine: A Breakthrough in the Treatment of Peptic Ulcer Disease
308(1)
Summary and Further Observations
309(4)
References
310(3)
Discovery of Potent Nonpeptide Vasopressin Receptor Antagonists
313(26)
Bruce E. Maryanoff
Introduction
313(2)
Genesis of the Vasopressin Receptor Antagonist Project
315(1)
Vasopressin, Its Receptors, and Disease
315(2)
The Game Plan
317(2)
Novel Chemotypes: Variations on a Theme
319(13)
Azepinoindoles
319(3)
Bridged Bicyclic Derivatives
322(2)
Thiazino-, Oxazino-, and Pyrazinobenzodiazepines
324(8)
Epilogue
332(7)
Acknowledgments
333(1)
References and Notes
333(6)
Discovery and Development of the Ultrashort-Acting Analgesic Remifentanil
339(14)
Paul L. Feldman
Introduction
339(1)
Discovery of Remifentanil
340(4)
Chemical Development of Remifentanil
344(5)
Human Clinical Trials with Remifentanil
349(4)
Acknowledgments
350(1)
References
350(3)
Discovery and Development of Nevirapine
353(12)
Karl Grozinger
John Proudfoot
Karl Hargrave
Introduction
353(2)
Lead Discovery and Optimization
355(2)
Chemical Development and Process Research
357(3)
Mechanism of Action
360(1)
Clinical Studies
361(4)
Acknowledgments
362(1)
References
362(3)
Applications of Nuclear Imaging in Drug Discovery and Development
365(18)
John W. Babich
William C. Eckelman
Introduction
365(1)
Process and Challenges of Drug Development
365(1)
Role and Contribution of Position Emission Tomography
366(1)
Principles and Evolution of Technology
366(2)
Introduction to PET Principles
366(1)
Suitable Targets
367(1)
Suitable Animal Models
367(1)
Role in Drug Discovery
368(8)
Target Validation and Drug Design
368(3)
Preclinical Studies
371(2)
Clinical Studies
373(3)
Summary and Outlook
376(7)
References
377(6)
Polymeric Sequestrants as Nonabsorbed Human Therapeutics
383(22)
Pradeep K. Dhal
Chad C. Huval
S. Randall Holmes-Farley
Introduction
383(1)
Polymers as Specific Molecular Sequestrants
384(1)
Sequestration of Inorganic Ions in the GI Tract
385(1)
Polymeric Potassium Sequestrants: A Nonabsorbed Therapy for Hyperkalemia
385(1)
Polymeric Drugs for Chronic Renal Failure
386(3)
Polymeric Iron Sequestrants for the Treatment of Iron Overload Disorders
389(3)
Sequestration of Bile Acids: Polymers as Cholesterol-Lowering Agents
392(4)
Sequestration of Pathogens: Polymeric Anti-infective Agents
396(1)
Sequestration of Toxins
397(3)
Polymeric Antimicrobial Agents
400(1)
Conclusions and Outlook
401(4)
References
402(3)
Botanical Immunomodulators and Chemoprotectants in Cancer Therapy
405(20)
Bhushan Patwardhan
Sham Diwanay
Manish Gautam
Introduction
405(1)
Immunomodulation
406(1)
Ethnopharmacology and Botanical Immunomodulators
406(1)
Adaptogens or Adjustive Medicine
407(2)
Botanicals with Adaptogenic Activity
407(1)
Rasayana Botanicals as Adaptogens
408(1)
Chemoprotection
409(8)
Drug Targets and Current Trends
409(1)
Chemoprotectants for Antimetabolites
410(1)
Thiol-Based Chemoprotectants for Cisplatin and Oxazophosphorine-Based Alkylating Agents
411(3)
Chemoprotectants for Anthracyclines
414(1)
Botanical Immunomodulators as Chemoprotectants
414(3)
Radioprotection
417(2)
Radioprotectants from Botanicals
418(1)
Botanical Immunomodulators as Antitumor Agents
418(1)
Conclusions
419(6)
References
420(5)
Index 425

Rewards Program

Write a Review