Case studies in modern drug discovery and development /

• Άλλοι συγγραφείς: Huang, Xianhai, Aslanian, Robert G.
• Μορφή: Ηλ. βιβλίο
• Γλώσσα: English
• Έκδοση: Hoboken, NJ : John Wiley & Sons, [2012]
• Θέματα: Drugs > Design.; Pharmaceutical chemistry.; Medical.; MEDICAL > Drug Guides.; MEDICAL > Nursing > Pharmacology.; MEDICAL > Pharmacology.; MEDICAL > Pharmacy.; Electronic books.

Learn why some drug discovery and development efforts succeed ... and others failWritten by international experts in drug discovery and development, this book sets forth carefully researched and analyzed case studies of both successful and failed drug discovery and development efforts, enabling medi...

Πίνακας περιεχομένων:

• CASE STUDIES IN MODERN DRUG DISCOVERY AND DEVELOPMENT; CONTENTS; PREFACE; CONTRIBUTORS; CHAPTER 1: INTRODUCTION: DRUG DISCOVERY IN DIFFICULT TIMES; CHAPTER 2: DISCOVERY AND DEVELOPMENT OF THE DPP-4 INHIBITOR JANUVIA; (SITA-GLIPTIN); 2.1 Introduction; 2.2 DPP-4 Inhibition as a Therapy for Type 2 Diabetes: Identification of Key Determinants for Efficacy and Safety; 2.2.1 Incretin-Based Therapy for T2DM; 2.2.2 Biological Rationale: DPP-4 is a Key Regulator of Incretin Activity; 2.2.3 Injectable GLP-1 Mimetics for the Treatment of T2DM.
• 2.2.11 DPP-4 Inhibitor Selectivity as a Key Parameter for Drug Development2.3 Medicinal Chemistry Program; 2.3.1 Lead Generation Approaches; 2.3.2 Cyclohexyl Glycine a-Amino Acid Series of DPP-4 Inhibitors; 2.3.3 Improving Selectivity of the a-Amino Acid Series; 2.3.4 Identification and Optimization of the ß-Amino Acid Series; 2.4 Synthetic and Manufacturing Routes to Sitagliptin; 2.4.1 Medicinal Chemistry Route to Sitagliptin and Early Modifications; 2.4.2 An Asymmetric Hydrogenation Manufacturing Route to Sitagliptin.
• 2.2.4 DPP-4 Inhibition as Oral Incretin-Based Therapy for T2DM2.2.5 Investigation of DPP-4 Biology: Identification of Candidate Substrates; 2.2.6 Preclinical Toxicities of In-Licensed DPP-4 Inhibitors; 2.2.7 Correlation of Preclinical Toxicity with Off-Target Inhibition of Pro-Specific Dipeptidase Activity; 2.2.8 Identification of Pro-Specific Dipeptidases Differentially Inhibited by the Probiodrug Compounds; 2.2.9 A Highly Selective DPP-4 Inhibitor is Safe and Well Tolerated in Preclinical Species; 2.2.10 A Highly Selective DPP-4 Inhibitor Does Not Inhibit T-Cell Proliferation in vitro.
• 2.4.3 A "Greener" Manufacturing Route to Sitagliptin Employing Biocatalytic Transamination2.5 Drug Product Development; 2.5.1 Overview; 2.5.2 Composition Development; 2.5.3 Manufacturing Process Development; 2.6 Clinical Studies; 2.6.1 Preclinical PD Studies and Early Clinical Development of Sitagliptin; 2.6.2 Summary of Phase II/III Clinical Trials; 2.7 Summary; References; CHAPTER 3: OLMESARTAN MEDOXOMIL: AN ANGIOTENSIN II RECEPTOR BLOCKER; 3.1 Background; 3.1.1 Introduction; 3.1.2 Prototype of Orally Active ARBs; 3.2 The Discovery of Olmesartan Medoxomil (Benicar); 3.2.1 Lead Generation.
• 3.2.2 Lead Optimization3.3 Characteristics of Olmesartan; 3.4 Binding Sites of Omlersartan to the AT1 Receptor and Its Inverse Agonoist Activity; 3.4.1 Binding Sites of Olmesartan to the AT1 Receptor; 3.4.2 Inverse Agonist Activity of Olmesartan; 3.4.3 Molecular Model of the Interaction between Olmesartan and the AT1 Receptor; 3.5 Practical Preparation of Olmesartan Medoxomil; 3.6 Preclinical Studies; 3.6.1 AT1 Receptor Blocking Action; 3.6.2 Inhibition of Ang II-Induced Vascular Contraction; 3.6.3 Inhibition of the Pressor Response to Ang II; 3.6.4 Blood Pressure Lowering Effects.