Analogue-based drug discovery III. (2012)

• Record Type: Book
• Further Information: Note: Edited by Janos Fischer, C. Robin Ganellin and David P. Rotella.
• Other Names: Fischer, János; Ganellin, C. R (C. Robin); Rotella, David P
• Contents: PREFACE; ; PART I: General Aspects; ; PIONEER AND ANALOGUE DRUGS; Monotarget Drugs; Dual-Acting Drugs; Multitarget Drugs; Summary; ; COMPETITION IN THE PHARMACEUTICAL DRUG DEVELOPMENT; Introduction; Analogue-Based Drugs: Just Copies?; How Often Does Analogue-Based Activity Occur? Insights from the GPCR Patent Space; ; METABOLIC STABILITY AND ANALOGUE-BASED DRUG DISCOVERY; Introduction; Metabolism-Guided Drug Design; Indirect Modulation of Metabolism by Fluorine Substitution; Modulation of Low Clearance/Long Half-Life via Metabolism-Guided Design; Tactics to Resolve Metabolism Liabilities Due to Non-CYP Enzymes; Eliminating RM Liabilities in Drug Design; Eliminating Metabolism-Dependent Mutagenicity; Eliminating Mechanism-Based Inactivation of CYP Enzymes; Identification (and Elimination) of Electrophilic Lead Chemical Matter; Mitigating Risks of Idiosyncratic Toxicity via Elimination of RM Formation; Case Studies on Elimination of RM Liability in Drug Discovery; Concluding Remarks; ; USE OF MACROCYCLES IN DRUG DESIGN EXEMPLIFIED WITH ULIMORELIN, A POTENTIAL GHRELIN AGONIST FOR GASTROINTESTINAL MOTILITY DISORDERS; Introduction; High-Throughput Screening Results and Hit Selection; Macrocycle Structure -; Activity Relationships; PK -; ADME Considerations; Structural Studies; Preclinical Evaluation; Clinical Results and Current Status; Summary; ; PART II: Drug Classes; ; THE DISCOVERY OF ANTICANCER DRUGS TARGETING EPIGENETIC ENZYMES; Epigenetics; DNA Methyltransferases; 5-Azacytidine (Azacitidine, Vidaza) and 5-Aza-20-deoxycytidine (Decitabine, Dacogen); Other Nucleoside DNMT Inhibitors; Preclinical; Zinc-Dependent Histone Deacetylases; Suberoylanilide Hydroxamic Acid (SAHA, Vorinostat, Zolinza); FK228 (Depsipeptide, Romidepsin, Istodax); Carboxylic Acid and Benzamide HDAC Inhibitors; Prospects for HDAC Inhibitors; Epigenetic Drugs - A Slow Start but a Bright Future; ; THIENOPYRIDYL AND DIRECT-ACTING P2Y12 RECEPTOR ANTAGONIST ANTIPLATELET DRUGS; Introduction; Thienopyridines; Direct-Acting P2Y12 Antagonists; cyclopropylamino]-5-(propylthio)-3H-[1, 2, 3]triazolo[4, 5-d]pyrimidin- 3-yl]-5-(2-hydroxyethoxy)cyclopentane-1, 2-diol; Summary; ; SELECTIVE ESTROGEN RECEPTOR MODULATORS; Introduction; Tamoxifen; Raloxifene; Summary; ; DISCOVERY OF NONPEPTIDE VASOPRESSIN V2 RECEPTOR ANTAGONISTS; Introduction; Peptide AVP Agonists and Antagonists; Lead Generation Strategies; Lead Generation Strategy-2, V2 Receptor Affinity; Lead Optimization; Reported Nonpeptide Vasopressin V2 Receptor Antagonist Compounds; Conclusions; ; THE DEVELOPMENT OF CYSTEINYL LEUKOTRIENE RECEPTOR ANTAGONISTS; Introduction; Scope of the Drug Discovery Effort on Leukotriene Modulators; Synthetic Leukotriene Production and Benefits Derived from this Effort; Bioassays and General Drug Discovery Testing Cascade; Development of Antagonists - General Approaches; Discovery of Zafirlukast; Discovery of Montelukast; Discovery of Pranlukast; Comparative Analysis and Crossover Impact; Postmarketing Issues; Conclusions; ; PART III: Case Studies; ; THE DISCOVERY OF DABIGATRAN ETEXILATE; Introduction; Dabigatran Design Story; Preclinical Pharmacology Molecular Mechanism of Action of Dabigatran; Clinical Studies and Indications; Summary; ; THE DISCOVERY OF CITALOPRAM AND ITS REFINEMENT TO ESCITALOPRAM; Introduction; Discovery of Talopram; Discovery of Citalopram; Synthesis and Production of Citalopram; The Pharmacological Profile of Citalopram; Clinical Efficacy of Citalopram; Synthesis and Production of Escitalopram; The Pharmacological Profile of the Citalopram Enantiomers; R-Citalopram's Surprising Inhibition of Escitalopram; Binding Site(s) for Escitalopram on the Serotonin Transporter; Future Perspectives on the Molecular Basis for Escitalopram?s Interaction with the SERT; Clinical Efficacy of Escitalopram; Conclusions; ; TAPENTADOL - FROM MORPHINE AND TRAMADOL TO THE DISCOVERY OF TAPENTADOL; Introduction; The Discovery of Tapentadol; The Preclinical and Clinical Profile of Tapentadol; Summary; ; NOVEL TAXANES: CABAZITAXEL CASE STUDY; Introduction; Cabazitaxel Structure -; Activity Relationships and Chemical Synthesis; Cabazitaxel Preclinical and Clinical Development; Summary; ; DISCOVERY OF BOCEPREVIR AND NARLAPREVIR: A CASE STUDY FOR ROLE OF STRUCTURE-BASED DRUG DESIGN; ; A NEW-GENERATION URIC ACID PRODUCTION INHIBITOR: FEBUXOSTAT; Introduction; Xanthine Oxidoreductase - Target Protein for Gout Treatment; Mechanism of XOR Inhibition by Allopurinol; Development of Nonpurine Analogue Inhibitor of XOR: Febuxostat; Mechanism of XOR Inhibition by Febuxostat; Excretion of XOR Inhibitors; Results of Clinical Trials of Febuxostat in Patients with Hyperuricemia and Gout; Summary; Added in proof; ; INDEX; ;
• Publisher Details: Place of publication not identified : Wiley-VCH
• Publication Date: 2012
• Extent: 1 online resource (404 pages)
• Subjects: 615.19; Drug development
• Languages: English
• ISBNs: 9783527651108
• Access Rights: Legal Deposit; Only available on premises controlled by the deposit library and to one user at any one time; The Legal Deposit Libraries (Non-Print Works) Regulations (UK).
• Access Usage: Restricted: Printing from this resource is governed by The Legal Deposit Libraries (Non-Print Works) Regulations (UK) and UK copyright law currently in force.