Chirality in Drug Design and Synthesis
- 1st Edition - November 20, 1990
- Imprint: Academic Press
- Editor: C. Brown
- Language: English
- eBook ISBN:9 7 8 - 1 - 4 8 3 2 - 8 8 2 4 - 6
Chirality in Drug Design and Synthesis is a collection of papers that discusses the property of asymmetry in the structural and synthetic chemistry of natural products, includ… Read more
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Request a sales quoteChirality in Drug Design and Synthesis is a collection of papers that discusses the property of asymmetry in the structural and synthetic chemistry of natural products, including the significance of chirality in medicinal chemistry. These papers examine the need for the preparation and study of pure enantiomers of chiral drug substances and their mechanism of interaction with enzymes and receptors. These papers also investigate the techniques in studying these interactions, as well as analyze the methods for their synthesis in enantiomerically pure form. One paper discusses the pharmacological and pharmacokinetic analyses made that point to the differences in the activity and disposition of enantiometric pairs. Another paper reviews the implications of the neglect of stereoselectivity at the different levels during the examination process of racemic drugs. Since no general guidelines exists for the development of drugs with chiral centers, one paper suggests a case-by-case approach in evaluating the safety and efficacy of drugs, particularly as regards how isomers differ in their effects. This collection is suitable for the pharmacologist, medicinal chemists, toxicologists, mechanistic chemists and synthetic organic chemists.
Contributors
Foreword
Introduction
1 Chirality: Pharmacological Action and Drug Development
1 Introduction
2 Terminology
3 Enantioselectivity in Pharmacological Activity
4 Enantioselectivity in Pharmacodynamics Resulting from Differences in the Pharmacokinetics of the Enantiomers
5 Conclusion
References
2 Racemic Therapeutics: Problems all Along the Line
1 Introduction
2 Implications of Chirality in Bioactive Agents
3 Clinical Pharmacology of Racemic Therapeutics
4 Ethical Aspects of Drug Development, Evaluation and Use
5 Noninformation and Disinformation in the Field of Chirality
6 Racemates as Drug Combinations
7 Perspectives
8 Summary
References
3 Chirality, Drug Metabolism and Action
1 Introduction
2 Stereochemistry and Drug Disposition
3 Stereoselective Metabolism and Drug Action
4 Conclusions
References
4 From Enzyme Mimics to Molecular Self-Assembly Processes
1 Introduction
2 A Gift from Nature
3 Needs of Enzyme Mimics
4 Serendipity Yet Again
5 A Chiral Crown Ether as a Reagent
6 The Same Chiral Crown Ether as a Catalyst
7 Coordination Through the Second Sphere
8 Planned Molecular Self-Assembly
9 From Host-Guest Chemistry to Molecular Assemblies
10 Structure-Directed Synthesis
11 The Future
Acknowledgments
References
5 Modeling of Drug-Receptor Interactions: Stereoselectivity of 5-Hydroxytryptamine and Dopamine Receptors in the Brain
1 Introduction
2 Interactions Between L-ZGP and 8-OH DPAT
3 Modeling of Drug-Receptor Interactions
4 DA D2-Receptor Agonists and Antagonists
5 5-HT1A-Receptor Agonists and Antagonists
Acknowledgments
References
6 Molecular Basis of the Activity of Antibiotics of the Vancomycin Group: Guides for Peptide-Peptide Binding
1 Introduction
2 Stereoselectivity
3 Peptide-Peptide Molecular Recognition
4 Approximate Binding Constants Estimated for Simple Carboxylic Acids
5 A Molecular Interpretation of the Binding Process
Acknowledgments
References
7 Recent Developments in the Use of Enzyme-catalysed Reactions in Organic Synthesis
1 Introduction
2 Recent Uses of Hydrolase Enzymes
3 Recent Uses of Oxidoreductase Enzymes
4 Enzyme-Catalysed Reactions Resulting in the Formation of Carbon-Carbon Bonds
5 Future Developments in the Area of Biotransformations
References
8 Recent Progress in Research on the Immunosuppressant FK-506
1 Isolation, Structure Determination and Stability of FK-506
2 Biological Activity
3 Synthetic Approaches to FK-506
References
9 A Practical, Enantioselective Synthesis of [R-(R*,S*)]-β-[(2-Carboxyethyl)thio]-α-hydroxy-2-(8-phenyloctyl)-benzenepropanoic acid (SK&F 104353), a Potent LTD4 Antagonist
1 Introduction
2 Background
3 Improvements in the Synthesis of 2-(phenyloctyl)benzaldehyde
4 Regioselective Epoxide Opening
5 Enantioselective Synthesis of an Epoxide Intermediate
6 Final Elaboration of SK&F 104353
Acknowledgments
References
10 Chirality Recognition in Synthesis
1 Introduction
2 Structure of the Chiral Iron Acetyl Complex [(C5H5)Fe(CO)(PPh3)COCH3]
3 Stereoselective Enolate Alkylation Reactions
4 Asymmetric Synthesis of Captopril and Epicaptopril
5 Asymmetric Synthesis of Differentially Protected α-alkylsuccinates
6 Asymmetric Synthesis of Actinonin and (—)-epiactinonin
7 Asymmetric Synthesis of Butyrolactones
8 Conclusions
Acknowledgments
References
11 Sultam-directed Asymmetric Synthesis of α-Amino Acids
1 Introduction
2 Alkylation of Glycinate Equivalents
3 Halogenation/Azide Displacement
4 Electrophilic 'Amination'
5 Conclusion
Acknowledgments
References
Appendix: Abstracts of Posters
Index
- Edition: 1
- Published: November 20, 1990
- No. of pages (eBook): 243
- Imprint: Academic Press
- Language: English
- eBook ISBN: 9781483288246
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