Cover

Cover
Series Page
Title Page
Copyright
eMagRes
International Advisory Board
Contributors
Series Preface
Preface
Abbreviations and Acronyms
Part A: Introduction
1. Chapter 1: Drug Discovery and Development: The Role of NMR
  1. 1.1 Introduction to Drug Discovery and Development and the Role of NMR
  2. 1.2 NMR Spectroscopy in Drug Discovery and Development
  3. 1.3 New Applications of NMR Spectroscopy in Pharmaceutical R&D
  4. 1.4 In vivo MRS and MRI
  5. 1.5 Future Developments
  6. References
Part B: NMR Theory & Experimental Methods
1. Chapter 2: Modern NMR Pulse Sequences in Pharmaceutical R&D
  1. 2.1 Introduction
  2. 2.2 Initial Sample Adjustments
  3. 2.3 One-dimensional Methods
  4. 2.4 Pulse Sequences for 2D NMR Spectroscopy
  5. 2.5 Conclusions
  6. Related Articles in eMagRes
  7. References
  8. Further Reading
2. Chapter 3: NMR Theory & Experimental MethodsExperimental NMR Methods for Pharmaceutical Research and Development
  1. 3.1 Introduction
  2. 3.2 NMR Hardware, Analytical Conditions
  3. 3.3 NMR-related Workflows
  4. 3.4 Quality Control
  5. 3.5 Conclusions
  6. Related Articles in eMagRes
  7. References
3. Chapter 4: 19F NMR Spectroscopy: Applications in Pharmaceutical Studies
  1. 4.1 Introduction
  2. 4.2 Practical Aspects of ¹⁹F NMR Spectroscopy
  3. 4.3 Small Molecule Studies of Pharmaceutical Interest
  4. 4.4 Application to Fluorine-Labeled Macromolecules
  5. 4.5 Drug Screening Activities
  6. 4.6 Applications in Drug Metabolism Studies
  7. 4.7 ¹⁹F NMR Spectroscopy In Vivo
  8. Related Articles in eMagRes
  9. References
4. Chapter 5: Quantitative NMR Spectroscopy in Pharmaceutical R&D
  1. 5.1 Introduction
  2. 5.2 Basic Principles of qNMR
  3. 5.3 Signal Separation/Overlap
  4. 5.4 Quantification Methods
  5. 5.5 Applications
  6. 5.6 Conclusion
  7. Acknowledgments
  8. References
5. Chapter 6: High-throughput NMR in Pharmaceutical R&D
  1. 6.1 Introduction
  2. 6.2 Overall Process View
  3. 6.3 Workflow – Purity and Identity of Solid Samples
  4. 6.4 Workflow – Purity and Identity of Screening Solutions
  5. 6.5 Workflow – Fragment-based Drug Discovery
  6. 6.6 Common Themes
  7. 6.7 Getting Faster
  8. 6.8 Summary
  9. References
6. Chapter 7: Multivariate Data Analysis Methods for NMR-based Metabolic Phenotyping in Pharmaceutical and Clinical Research
  1. 7.1 Introduction
  2. 7.2 Raw Analytical Signal Processing
  3. 7.3 Exploratory Analysis of H NMR-based Metabolic Phenotypes
  4. 7.4 Predictive Analysis of H NMR-based Metabolic Phenotypes
  5. 7.5 Time-course Analysis of NMR-based Metabolic Phenotypes
  6. 7.6 Conclusions
  7. Related Articles in eMagRes
  8. References
Part C: Idea to Lead
1. Chapter 8: The Role of NMR in Target Identification and Validation for Pharmaceutical R&D
  1. 8.1 Introduction: What is Drug Discovery?
  2. 8.2 Drug Targets
  3. 8.3 Target Identification and Validation
  4. 8.4 Application of NMR in Target Identification and Validation
  5. Acknowledgments
  6. References
2. Chapter 9: High-resolution MAS NMR of Tissues and Cells
  1. 9.1 Introduction
  2. 9.2 The Developments
  3. 9.3 Applications
  4. 9.4 Conclusions
  5. Related Articles in eMagRes
  6. References
3. Chapter 10: NMR Studies of Inborn Errors of Metabolism
  1. 10.1 Introduction
  2. 10.2 Body Fluid NMR
  3. 10.3 Applications of NMR in IEM Diagnosis
  4. Related Articles in eMagRes
  5. References
4. Chapter 11: NMR-based Structure Confirmation of Hits and Leads in Pharmaceutical R&D
  1. 11.1 Introduction
  2. 11.2 Why Is It Necessary?
  3. 11.3 When Should the Structure Confirmation Be Carried Out?
  4. 11.4 What Are the Benefits?
  5. 11.5 How Is Structure Confirmation Carried Out?
  6. 11.6 How Bad Can It Get?
  7. 11.7 Conclusion
  8. Related Articles in eMagRes
  9. References
5. Chapter 12: Fragment-based Drug Design Using NMR Methods
  1. 12.1 Introduction
  2. 12.2 Fragment-based Drug Design vs High-throughput Screening
  3. 12.3 FBDD Approaches
  4. 12.4 Fragment Library
  5. 12.5 Target Druggability
  6. 12.6 Target-based vs Ligand-based FBDD NMR Methods
  7. 12.7 Protein Target Production
  8. 12.8 NMR-based Screening Experiments
  9. 12.9 ¹⁹F NMR Screening
  10. 12.10 Hit Validation by NMR and Validation of NMR Fragment Hits
  11. 12.11 Nonspecific Binding
  12. 12.12 Fragment Prioritization
  13. 12.13 Hit-to-Lead
  14. 12.14 Linker Design
  15. 12.15 Protein–Ligand Affinities
  16. 12.16 Protein–Ligand Structure Determination
  17. 12.17 Clinical Candidates Originating from FBDD
  18. Related Articles in eMagRes
  19. References
6. Chapter 13: Hit Discovery from Natural Products in Pharmaceutical R&D
  1. 13.1 Introduction
  2. 13.2 Practical Aspects of NMR Spectroscopic Experiments on Natural Products
  3. 13.3 Advances in NMR Acquisition and Data Processing
  4. 13.4 ¹H NMR Spectroscopic Screening of Natural Product Extracts
  5. 13.5 Micro NMR Spectroscopy and Cryogenic NMR Probes
  6. 13.6 NMR Spectroscopy of Natural Products Following Chromatography
  7. 13.7 Dereplication and Natural Product NMR Databases
  8. 13.8 Conclusions
  9. Related Articles in eMagRes
  10. References
Part D: Lead to Drug Candidate
1. Chapter 14: NMR-based Structure Determination of Drug Leads and Candidates
  1. 14.1 Introduction
  2. 14.2 Background to Structure Determination by NMR in the Pharmaceutical Industry
  3. 14.3 Information from NMR Experiments for Structure Determination
  4. 14.4 Constitution. Use of C NMR Chemical Shift Predictions and H–C Chemical Shift Correlations from HSQC and HMBC Spectra
  5. 14.5 Stereochemistry Problems. Proton–Proton Through-space Correlations
  6. 14.6 Use of the N Isotope
  7. 14.7 Examples Where H NMR Spectra are Broad or Contain More than One Species in Solution
  8. 14.8 Conclusions
  9. References
2. Chapter 15: Mixture Analysis in Pharmaceutical R&D Using Hyphenated NMR Techniques
  1. 15.1 Introduction
  2. 15.2 Practical and Technical Considerations in LC–NMR
  3. 15.3 High-performance Liquid Chromatography–Nuclear Magnetic Resonance–Mass Spectrometry (HPLC–NMR–MS)
  4. 15.4 Applications of LC–NMR
  5. 15.5 Conclusions
  6. Related Articles in eMagRes
  7. References
3. Chapter 16: Conformation and Stereochemical Analysis of Drug Molecules
  1. 16.1 Introduction
  2. 16.2 Experimental Techniques
  3. 16.3 Analysis of NMR Results
  4. 16.4 Applications of Stereochemical and Conformational Studies in the Pharmaceutical Industry
  5. 16.5 Conclusions
  6. Acknowledgments
  7. Related Articles in eMagRes
  8. References
4. Chapter 17: NMR Methods for the Assignment of Absolute Stereochemistry of Bioactive Compounds
  1. 17.1 Introduction
  2. 17.2 The Absolute Configuration and NMR Spectra
  3. 17.3 CDAs and Substrates
  4. 17.4 The Use of ¹³C NMR for Assignment
  5. 17.5 The Assignment of Absolute Configuration of Monofunctional Compounds by Double Derivatization
  6. 17.6 Single Derivatization Methods for Alcohols and Amines
  7. 17.7 The Assignment of Polyfunctional Compounds
  8. Related Articles in eMagRes
  9. References
5. Chapter 18: Applications of Preclinical MRI/MRS in the Evaluation of Drug Efficacy and Safety
  1. 18.1 Introduction
  2. 18.2 Review of MRI/MRS Methods
  3. 18.3 Applications of MRI/MRS in Drug Discovery
  4. 18.4 Conclusions
  5. 18.5 Disclaimer
  6. 18.6 Conflict of Interests
  7. Acknowledgment
  8. Related Articles in eMagRes
  9. References
6. Chapter 19: Practical Applications of NMR Spectroscopy in Preclinical Drug Metabolism Studies
  1. 19.1 Introduction
  2. 19.2 NMR in the Realm of ADME Discovery
  3. 19.3 Metabolite Concentrations versus Instrument Sensitivity
  4. 19.4 Sample Isolation
  5. 19.5 Quantitative NMR (qNMR) Spectroscopy
  6. 19.6 Discussion
  7. References
7. Chapter 20: Preclinical Drug Efficacy and Safety Using NMR Spectroscopy
  1. 20.1 Introduction
  2. 20.2 Sample Types
  3. 20.3 Statistical Analysis of Metabonomic Data
  4. 20.4 Organ-specific Toxicities by NMR Spectroscopy-based Metabonomics
  5. 20.5 The COMET Consortium Project
  6. 20.6 Toxico/pharmacometabonomics
  7. 20.7 Conclusions
  8. References
8. Chapter 21: Characterization of Pharmaceutical Compounds by Solid-state NMR
  1. 21.1 Introduction
  2. 21.2 Basic Experimental Methods
  3. 21.3 Emerging Experimental Methods
  4. 21.4 Crystalline Phases of Drug Substances and Excipients
  5. 21.5 Amorphous Phases of Drug Substances and Excipients
  6. 21.6 Drug Products
  7. 21.7 Conclusion
  8. Acknowledgments
  9. Related Articles in eMagRes
  10. References
9. Chapter 22: Structure-based Drug Design Using NMR
  1. 22.1 Introduction
  2. 22.2 Protein Kinases
  3. 22.3 Protein Tyrosine Phosphatase 1B (PTP1B)
  4. 22.4 Ras Superfamily
  5. 22.5 Conclusions
  6. Acknowledgments
  7. References
10. Chapter 23: Pharmaceutical Technology Studied by MRI
  1. 23.1 Introduction
  2. 23.2 Practicalities
  3. 23.3 Applications
  4. 23.4 Future Developments
  5. 23.5 End Note
  6. Acknowledgments
  7. References
  8. Further Reading
Part E: Clinical Development
1. Chapter 24: NMR-based Metabolic Phenotyping for Disease Diagnosis and Stratification
  1. 24.1 Introduction
  2. 24.2 NMR Spectroscopy and Metabolic Phenotyping
  3. 24.3 Conclusion
  4. Acknowledgments
  5. References
2. Chapter 25: NMR-based Pharmacometabonomics: A New Approach to Personalized Medicine
  1. 25.1 Introduction to Personalized Medicine
  2. 25.2 Introduction to Metabonomics and Pharmacometabonomics
  3. 25.3 The First Demonstrations of Pharmacometabonomics
  4. 25.4 The Current Status of Pharmacometabonomics
  5. 25.5 Future Developments and Predictive Metabonomics
  6. References
3. Chapter 26: Clinical MRI Studies of Drug Efficacy and Safety
  1. 26.1 Introduction
  2. 26.2 Biomarkers and Surrogate Markers
  3. 26.3 Phases of Clinical Trials
  4. 26.4 Therapeutic Areas
  5. 26.5 Clinical Trials Conduct: Specific Considerations
  6. 26.6 Future Developments
  7. Acknowledgments
  8. References
  9. Further Reading
4. Chapter 27: The Role of NMR in the Protection of Intellectual Property in Pharmaceutical R&D
  1. 27.1 Introduction
  2. 27.2 Patent Rights
  3. 27.3 Solution-state NMR
  4. 27.4 Solid-state NMR
  5. 27.5 Magnetic Resonance Imaging
  6. 27.6 Conclusion
  7. 27.7 Disclaimer
  8. Acknowledgment
  9. Related Articles in eMagRes
  10. References
Part F: Drug Manufacture
1. Chapter 28: Analysis of Counterfeit Medicines and Adulterated Dietary Supplements by NMR
  1. 28.1 Introduction
  2. 28.2 Heparin
  3. 28.3 Antimalarial Drugs
  4. 28.4 Phosphodiesterase-5 Inhibitors (PDE5i)
  5. 28.5 Slimming Products
  6. 28.6 Anti-inflammatory Herbal Medicines
  7. 28.7 Corticosteroids
  8. 28.8 Isotopic NMR
  9. 28.9 Conclusion
  10. Acknowledgements
  11. Related Articles in eMagRes
  12. References
2. Chapter 29: Pharmaceutical Industry: Regulatory Control and Impact on NMR Spectroscopy
  1. 29.1 Introduction
  2. 29.2 The Regulatory Dossier
  3. 29.3 Information Required to Establish the Quality of Drug Substance and Drug Product
  4. 29.4 NMR Spectroscopy in the Regulatory Dossier
  5. 29.5 Presentation of NMR Data
  6. 29.6 Common Pitfalls
  7. 29.7 Concluding Remarks
  8. References
3. Chapter 30: NMR Spectroscopy in the European and US Pharmacopeias
  1. 30.1 Introduction
  2. 30.2 Pharmacopoeial Monographs
  3. 30.3 NMR Spectroscopy in the European Pharmacopoeia
  4. 30.4 NMR Spectroscopy in the United States Pharmacopeia
  5. 30.5 Historical Perspective
  6. 30.6 Examples of NMR Spectroscopy in Monographs for Drug Substances and Drug Products
  7. 30.7 Conclusion
  8. Acknowledgment
  9. References
4. Chapter 31: NMR in Pharmaceutical Manufacturing
  1. 31.1 Introduction
  2. 31.2 Quality Control
  3. 31.3 Troubleshooting
  4. Acknowledgment
  5. References
5. Index
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