Progress in medicinal chemistry. Volume 44 /

The perceived lack of drug discovery productivity in recent times has led to much debate in the pharmaceutical/biotechnology industry as escalating R & D costs are not being matched by increased output. Few observers doubt that selecting the right targets, ie those which are critical to disease...

Πλήρης περιγραφή

Λεπτομέρειες βιβλιογραφικής εγγραφής
Άλλοι συγγραφείς: King, Frank D., Lawton, G.
Μορφή: Ηλ. βιβλίο
Γλώσσα:English
Έκδοση: Amsterdam ; Boston : Elsevier, 2006.
Σειρά:Progress in Medicinal Chemistry ; v. 44.
Θέματα:
Διαθέσιμο Online:Full Text via HEAL-Link
Πίνακας περιεχομένων:
  • Cover
  • Preface
  • Contents
  • List of Contributors
  • Finding Protein Kinase Hits using Structural Information
  • Introduction
  • Screening by X-ray Crystallography
  • Screening by NMR
  • Fundamentals of NMR Spectroscopy
  • Using Chemical Shift Changes
  • Nuclear-Spin Relaxation
  • Nuclear Overhauser Effects
  • Exchange Phenomena
  • Applications of NMR in Screening
  • Target-Based Screening
  • Ligand-Based Screening
  • Examples of NMR Methods for Discovering Kinase Inhibitors
  • The Shapes Strategy
  • NMR Screening by Waterlogsy Method
  • NMR Screening of Protein Kinases by ATP-STD Method
  • NMR Backbone Assignment of a Kinase
  • Designing Novel Kinase Inhibitors from the NMR-Based Screening of Fragments
  • Design of Libraries for use in NMR Screening
  • In Silico Methods
  • Receptor-Based Screening
  • Compound Database and Receptor Preparation
  • Protein-Ligand Docking
  • Scoring Functions
  • Development and Evaluation of Docking and Scoring
  • Virtual Screening and Protein Kinases
  • Faults and Fixes for Virtual Screening
  • Consensus Scoring
  • Knowledge-Based Screening
  • Protein Flexibility and Induced Fit
  • High Throughput Docking as a Virtual Screening Tool
  • Alternatives to High Throughput Docking
  • Comparative Homology Modelling
  • De Novo Design
  • Summary
  • References
  • Blunting the Swiss Army Knife of Hepatitis C Virus: Inhibitors of NS3/4A Protease*
  • Hepatitis C Infection
  • Introduction
  • The Hepatitis C Virus
  • Current Therapies for the Treatment of HCV Infections
  • The HCV NS3/4A Protease
  • Tools to Study NS3/4A Protease Inhibitors
  • Enzymatic Assays
  • Viral Replication
  • Inhibitors of the NS3/4A Serine Protease
  • Non-Covalent Peptidic Inhibitors
  • Covalent Reversible Peptidic Inhibitors
  • Non-Peptidic Inhibitors
  • Summary and Outlook
  • References
  • Peptide Deformylase Inhibitors
  • Introduction
  • Peptide Deformylase as a Novel Antibacterial Target
  • Function
  • Essentiality
  • Spectrum
  • Selectivity
  • Protein Structure of Peptide Deformylases
  • Three-Dimensional Structure
  • Metal-Binding Site
  • Comparison with Other Metalloproteases
  • Substrate-Binding Pockets
  • Design and SAR of Peptide Deformylase Inhibitors
  • Early Substrate-Based Inhibitors
  • Pseudopeptidic Hydroxamic Acids and N-Formyl-N-Hydroxylamines
  • Non-Peptidic Templates
  • Clinical Candidates
  • BB-83698
  • LBM-415
  • Summary and Perspectives
  • Acknowledgements
  • References
  • Clinically Useful Vanilloid Receptor TRPV1 Antagonists: Just around the Corner (or too Early to Tell)?
  • Introduction
  • The Theory: Can TRPV1 Antagonists Function as Clinically useful Drugs? (The Pros and The Cons)
  • TRPV1 Antagonists: an Overview of Chemistry and Pharmacology
  • Iodinated Capsaicinoids and Resiniferonoids
  • 4-Heteroarylpiperazine-1-Carboxyarylamides
  • N-Arylcinnamides
  • N-(Aza)naphthyl-N'-aryl(benzyl)ureas
  • N-Aryl-N'-Alkylaminocarbonyl Ethylendiamines
  • N, N'-Dibenzylthioureas
  • Miscellaneous Natural and Endogenous Products
  • Miscellaneous Structures from the Proprietary Literature
  • Potential Clinical Indications for TRPV1 Blockade
  • Chronic, Intractable Pa.