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| Contributors | |
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| Preface | |
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| From Patent to Prescription: Paving the Perilous Path to Profit | |
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| Introduction | |
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| A Simple Solution to a Complex Problem | |
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| An Intriguing Patent Problem | |
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| Another Structural Insight | |
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| References | |
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| Medicinal Chemistry in the New Millennium: A Glance into the Future | |
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| Introduction | |
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| Practice of Medicinal Chemistry | |
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| Emergence as a Formalized Discipline | |
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| Early Developments | |
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| Present Status | |
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| Examples Involving Site-Directed Mutagenesis | |
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| Latest Trends | |
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| Evolving Drug Discovery and Development Process | |
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| Working Defi nition for Medicinal Chemistry | |
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| Immediate- and Long-Term Roles for Medicinal Chemistry | |
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| Pursuing Efficacy | |
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| Gathering Positive, Neutral, and Negative SARs During HTS | |
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| Example Involving Multidrug Resistance of Anticancer Agents | |
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| Compound Libraries: Example of Working with Nature to Enhance Molecular Diversity | |
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| Assessing and Handling Molecular Conformation | |
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| Chemoinformatics | |
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| Obtaining Chemically Correct 3D Structures | |
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| Infl uence of Biological Environments: Example Involving Drug Metabolism | |
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| Dynamic Energy Relationships: Example Involving a Small Ring System | |
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| Druglike Properties and Privileged Structures | |
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| Tiered Structural Information and Searching Paradigms | |
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| ADMET Considerations | |
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| Assuring Absorption | |
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| Directing Distribution | |
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| Herbal Remedies: Example of Working with Nature to Discover | |
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| ADMET-Related Synergies, 59 | |
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| Brute Force HTS to Uncover Multicomponent Synergies | |
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| Controlling Metabolism: Example Involving a Soft Drug Strategy | |
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| Optimizing Excretion | |
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| Avoiding Toxicity | |
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| Weighting Decision Criteria from Effi cacy and ADMET SAR | |
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| Process Chemistry Considerations | |
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| Cost and Green Chemistry | |
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| Defi ning Stereochemistry: Example Involving Benzylamine Chiral Auxiliary Synthetic Reagents | |
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| Analytical Chemistry/X-ray Diffraction | |
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| Latest Trends | |
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| Examples Involving Dopamine Receptors, c-AMP Phosphodiesterase Enzymes, and the Dynamics of Protein Folding | |
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| Summary | |
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| General Points | |
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| Attributes of Drug Discovery Libraries, Compound Hits, and Lead Compounds | |
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| Formalized Instruction of Medicinal Chemistry | |
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| Intellectual Property Considerations | |
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| Knowledge Versus Diversity Paradox | |
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| Acknowledgments | |
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| References and Notes | |
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| Contemporary Drug Discovery | |
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| Introduction | |
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| Getting Started | |
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| Characteristics of a Suitable Lead Substance | |
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| Potency and Selectivity | |
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| Structure-Activity Relationships | |
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| Toxicity | |
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| Changing Appellation of the Best in Series: Analog Attrition | |
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| Some Criteria That a Hit Must Satisfy to Become a Drug | |
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| Level of Potency | |
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| Comparison of Potency and Efficacy | |
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| Druglike Character | |
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| Effi cacy Following Oral Administration | |
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| Lipinski Rules for Oral Absorption | |
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| Injectable Medications | |
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| Distribution | |
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| Serum Protein Binding | |
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| Metabolism | |
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| Distribution | |
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| Excretion | |
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| Patenting | |
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| Pharmaceutical Properties | |
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| Idiosyncratic Problems | |
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| Summary | |
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| Example of Drug Development That Illustrates Many of the Aforementioned Considerations | |