The Practice of Medicinal Chemistry

BiographySection EditorsContributorsPreface to the First EditionPreface to the Second EditionPreface to the Third EditionPart I General Aspects of Medicinal Chemistry1. A History of Drug DiscoveryI. IntroductionII. Two Hundred Years of Drug DiscoveriesIII. Considerations on Recent Trends in Drug DiscoveryReferences2. Medicinal Chemistry: Definitions and Objectives, Drug Activity Phases, Drug Classification SystemsI. Definitions and ObjectivesII. Drug Activity PhasesIII. Drug Classification SystemsReferences3. Measurement and Expression of Drug EffectsI. IntroductionII. In Vitro ExperimentsIII. Ex Vivo ExperimentsIV. In Vivo ExperimentsReferences4. Molecular Drug TargetsI. IntroductionII. Enzymes as Drug TargetsIII. Membrane Transporters as Drug TargetsIV. Voltage-Gated Ion Channels as Drug TargetsV. Non-Selective Cation Channels as Drug TargetsVI. Direct Ligand-Gated Ion Channels (Receptors with Intrinsic Ion Channel)VII. Receptors with Intrinsic Enzyme ActivityVIII. Receptors Coupled to Various Cytosolic ProteinsIX. G-Protein-Coupled ReceptorsX. Nuclear Receptors As Drug TargetsReferences5. Drug Targets, Target Identification, Validation and ScreeningI. IntroductionII. Improving the Resolution of Disease EtiologyIII. Biopharmaceutical TherapiesIV. Drug Target IdentificationV. Hit-to-LeadVI. Clinical BiomarkersVII. ConclusionsReferences Part II Lead Compound Discovery Strategies6. Strategies in the Search for New Lead Compounds or Original Working HypothesesI. IntroductionII. First Strategy: Analog DesignIII. Second Strategy: Systematic ScreeningIV. Third Strategy: Exploitation of Biological InformationV. Fourth Strategy: Planned Research and Rational ApproachesVI. ConclusionReferences7. High-Throughput Screening and Drug DiscoveryI. IntroductionII. Historical BackgroundIII. From Screen to LeadIV. Examples of Drugs Derived from Screening LeadsV. Practical Application, Recent ExampleVI. ConclusionReferences8. Natural Products as Pharmaceuticals and Sources for Lead StructuresI. IntroductionII. The Importance of Natural Products in Drug Discovery and DevelopmentIII. The Design of an Effective Natural-Products-Based Approach to Drug DiscoveryIV. Examples of Natural Products or Analogs as DrugsV. Future Directions in Natural Products as Drugs and Drug Design TemplatesVI. SummaryReferences9. Biology Oriented Synthesis and Diversity Oriented Synthesis in Compound Collection DevelopmentI. IntroductionII. Diversity Oriented SynthesisIII. Biology Oriented SynthesisIV. Conclusion and OutlookReferences10. In Silico Screening: Hit Finding from Database MiningI. IntroductionII. Representation of Chemical StructuresIII. Data Mining MethodsIV. Database SearchesV. ApplicationsVI. Conclusion and Future DirectionsReferences11. Fragment-Based Drug DiscoveryI. Ligand-Protein Interactions: First PrinciplesII. Status of Late 1990s Drug Discovery in the Pharmaceutical IndustryIII. What is FBDD?IV. Creation and Analysis of FBDD LibrariesV. Nuclear Magnetic ResonanceVI. X-ray CrystallographyVII. Other Biophysical and Biochemical Screening MethodsVIII. Methods for Fragment Hit Follow-UpIX. Trends for the FutureReferences12. Lead-Likeness and Drug-LikenessI. IntroductionII. Assessing " Drug-Likeness III. Selecting Better Leads: " Lead-Likeness IV. ConclusionReferences13. Web Alert: Using the Internet for Medicinal ChemistryI. IntroductionII. BlogsIII. WikisIV. Compound InformationV. Biological Properties of CompoundsVI. Drug InformationVII. Physical Chemical InformationVIII. Prediction and Calculation of Molecular PropertiesIX. Chemical SuppliersX. Chemical SynthesisXI. Chemical Software ProgramsXII. AnalysisXIII. Chemical PublicationsXIV. Patent InformationXV. ToxicologyXVI. Metasites and Technology Service Provider DatabasesPart III Primary Exploration of Structure-Activity Relationships14. Molecular Variations in Homologous Series: Vinylogues and BenzologuesI. Homologous SeriesII. Vinylogues and BenzologuesReferences15.