Retaining the successful approach found in the previous volume in this series, the inventors and primary developers of drugs that successfully made it to market tell the story of the drug?s discovery and development and relate the often twisted route from the first candidate molecule to the final marketed drug. 11 selected case studies describe recently introduced drugs that have not been previously covered in textbooks or general references. These range across six different therapeutic fields and provide a representative cross–section of the current drug development efforts. Backed by copious data and chemical information, the insight and experience of the contributors makes this one of the most useful training manuals that a junior medicinal chemist can hope to find and has won the support and endorsement of IUPAC. INDICE: PART I. HDAC Inhibitor Anticancer Drug Discovery. . FROM DMSO TO THE ANTICANCER COMPOUND SAHA, AN UNUSUAL INTELLECTUAL PATHWAY FOR DRUG DESIGN. Introduction. The Discovery of SAHA (vorinostat). Clinical Trials. Follow–On Research –. Selective HDAC Inhibitors. Conclusion. . ROMIDEPSIN AND THE ZINC–BINDING THIOL FAMILY OF NATURAL PRODUCT HDAC INHIBITORS. Histone Deacetylases as a Therapeutic Target. The Discovery and Development of Romidepsin. The Zinc–Binding Thiol Family of Natural Product HDAC Inhibitors. Synthetic Analogues of the Zinc–Binding Thiol Natural Products. Summary. . THE DISCOVERY AND DEVELOPMENT OF BELINOSTAT. Introduction. Discovery of Belinostat. Belinostat Biological Profiling. Formulation Development. Clinical Development. Conclusions. . DISCOVERY AND DEVELOPMENT OF FARYDAK (NVP–LBH589, PANOBINOSTAT) AS AN ANTICANCER DRUG. Target Identification: From p21Wafl Induction to HDAC Inhibition. Program Flowchart Assays for Drug Discovery. Hit–To–Lead Campaign: Trichostatin A to LAK974. Lead Optimization: LAK974 to LAQ824. Profiling LAQ824 for Cancer Therapy. Preclinical Development of LAQ824. LAQ824 Follow–Up. Discovery of LBH589. Safety Profile for LBH589. Pan–HDAC Inhibition by LBH589. Cancer Cell–Specific Cytotoxicity of LBH589. . DISCOVERY AND DEVELOPMENT OF HDAC SUBTYPE SELECTIVE INHIBITOR CHIDAMIDE: POTENTIAL IMMUNOMODULATORY ACTIVITY AGAINST CANCER. Introduction. Discovery of Chidamide. Molecular Mechanisms of Chidamide. Animal Studies. Clinical Development. Future Perspective. . PART II. Steroidal CYP17 Inhibitor Anticancer Drug Discovery. . ABIRATERONE ACETATE (ZYTIGA): AN INHIBITOR OF CYP17 AS A THERAPEUTIC FOR CASTRATION–RESISTANT PROSTATE CANCER. Introduction. Discovery and Structure–Activity Relationships (SAR). Preclinical Characterisation of Abiraterone. Physical Characterisation. Clinical Studies. Conclusion. . PART III. Anti–Infective Drug Discoveries. . DISCOVERY OF DELAMANID FOR THE TREATMENT OF MULTIDRUG–RESISTANT PULMONARY TUBERCULOSIS. Introduction. Synthesis Strategy. Synthesis Route. Screening Evaluations. Preclinical Data of Delamanid. Clinical Data of Delamanid. Future Priorities and Conclusion. . SOFOSBUVIR: THE DISCOVERY OF A CURATIVE THERAPY FOR THE TREATMENT OF HEPATITIS C VIRUS. Introduction. Discussion. Conclusion. . PART IV. Central Nervous System (CNS) Drug Discovery. . THE DISCOVERY OF THE ANTIDEPRESSANT VORTIOXETINE AND THE RESEARCH THAT UNCOVERED ITS POTENTIAL TO TREAT THE COGNITIVE DYSFUNCTION ASSOCIATED WITH DEPRESSION. Introduction. The Discovery of Vortioxetine. Clinical Development of Vortioxetine for the Treatment of MDD. Uncovering Vortioxetine?s Potential to Treat Cognitive Dysfunction in Patients with MDD. Conclusion. . PART V. Antiulcer Drug Discovery. . DISCOVERY OF VONOPRAZAN FUMARATE (TAK–438) AS A NOVEL, POTENT AND LONG–LASTING POTASSIUM–COMPETITIVE ACID BLOCKER. Introduction. Limitations of PPIs and the Possibility of P–CABs. Exploration of Seed Compounds. Lead Generation from HTS Hit Compound 1. Analysis of SAR and Structure–Toxicity Relationship for Lead Optimization. Selection of Vonoprazan Fumarate (TAK–438) as a Candidate Compound. Preclinical Studiy of TAK–438. Clinical Study of TAK–438. Discussion. Conclusion. . PART VI. Cross–Therapeutic Drug Discovery (Respiratory Diseases/Anti–Cancer). . DISCOVERY AND DEVELOPMENT OF NINTEDANIB: A NOVEL ANTIANGIOGENIC AND ANTIFIBROTIC AGENT. Introduction. Structure–Activity Relationships of Oxindole Kinase Inhibitors and the Discovery of Nintedanib. Structural Research. Preclinical Pharmacodynamic Exploration. Nonclinical Drug Metabolism and Pharmacokinetics. Clinical Pharmacokinetics. Toxicology. Phase III Clinical Data. Other Oncology Studies. Conclusions. . Index
- ISBN: 978-3-527-34115-3
- Editorial: Wiley VCH
- Encuadernacion: Rústica
- Páginas: 292
- Fecha Publicación: 23/11/2016
- Nº Volúmenes: 1
- Idioma: Inglés