Progress in medicinal chemistry. Volume 44 /

• 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: Pharmaceutical chemistry.; MEDICAL > Drug Guides.; MEDICAL > Pharmacology.; MEDICAL > Pharmacy.; MEDICAL > Nursing > Pharmacology.; Electronic books.

 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 pathology and are 'druggable', is the best starting point for improved productivity. The seven chapters of this volume describe recent progress towards drugs acting at a range of 'druggable' targets. One chapter addresses kinases, one covers an ion channel, two proteases are featured and three of the chapt. 

 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.