Most drugs are analogue drugs. There are no general rules how a new drug can be discovered, nevertheless, there are some observations which help to find a new drug, and also an individual story of a drug discovery can initiate and help new discoveries. Volume III is a continuation of the successful book series with new examples of established and recently introduced drugs. The major part of the book is written by key inventors either as a case study or a study of an analogue class. With its wide range across a variety of therapeutic fields and chemical classes, this is of interest to virtually every researcher in drug discovery and pharmaceutical chemistry, and -- together with the previous volumes -- constitutes the first systematic approach to drug analogue development.

Table of 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