• Volume 1: General Perspective - The Future of Drug Discovery Volume 2: Drug Discovery Technologies Volume 3: In Silico Drug Discovery Tools Volume 4: Experimental ADME and Toxicology Volume 5: Cancer, Immunology and Inflammation, and Infectious Disease Volume 6: CNS, Pain, Metabolic Syndrome, Urology, Gastrointestinal and Cardiovascular Volume 7: Biologics Medicine Volume 8: Case Histories in Recent Drug Discovery.
• (source: Nielsen Book Data)9780128032008 20170724

Comprehensive Medicinal Chemistry III, Third Edition provides a contemporary and forward looking critical analysis and summary of recent developments, emerging trends, and recently identified new areas where medicinal chemistry is having an impact. The discipline of medicinal chemistry continues to evolve as it adapts to new opportunities and strives to solve new challenges. These include drug targeting, biomolecular therapeutics, development of chemical biology tools, data collection and analysis, in silico models as predictors for biological properties, identification and validation of new targets, approaches to quantify target engagement, new methods for synthesis of drug candidates such as green chemistry, development of novel scaffolds for drug discovery, and the role of regulatory agencies in drug discovery.
(source: Nielsen Book Data)9780128032008 20170724

Despite considerable technological advances, the pharmaceutical industry is experiencing a severe innovation deficit, especially in the discovery of new drugs. Innovative Approaches in Drug Discovery: Ethnopharmacology, Systems Biology and Holistic Targeting provides a critical review and analysis of health, disease and medicine, and explores possible reasons behind the present crisis in drug discovery. The authors illustrate the benefits of systems biology and pharmacogenomics approaches, and advocate the expansion from disease-centric discovery to person-centric therapeutics involving holistic, multi-target, whole systems approaches. This book lays a path for reigniting pharmaceutical innovation through a disciplined reemergence of pharmacognosy, embracing open innovation models and collaborative, trusted public-private partnerships. With unprecedented advances made in the development of biomedically-relevant tools and technologies, the need is great and the time is now for a renewed commitment towards expanding the repertoire of medicines.ïŽ By incorporating real-life examples and state-of-the-art reviews, this book provides valuable insights into the discovery and development strategies for professionals, academicians, and students in the pharmaceutical sciences.

• Preface ix Companion Website Directions xii 1. Introduction: Basic Concepts 1 1.1 Introduction 1 1.2 Drugs and drug nomenclature 3 1.3 Law of mass action 4 1.4 Ionization 9 1.5 Partition coefficients 12 1.6 Further reading 14 2. Drug Administration and Distribution 15 2.1 Introduction 15 2.2 Drug transfer across biological membranes 16 2.3 Drug administration 22 2.4 Drug distribution 31 2.5 Plasma protein binding 38 2.6 Further reading 43 2.7 References 43 3. Drug Metabolism and Excretion 45 3.1 Introduction 45 3.2 Metabolism 46 3.3 Excretion 58 3.4 Further reading 69 3.5 References 69 4. Single compartment Pharmacokinetic Models 71 4.1 Introduction 72 4.2 Systemic clearance 74 4.3 Intravenous administration 76 4.4 Absorption 79 4.5 Infusions 87 4.6 Multiple doses 90 4.7 Non linear kinetics 94 4.8 Relationship between dose, and onset and duration of effect 98 4.9 Limitations of single compartment models 99 4.10 Further reading 100 4.11 References 100 5. Multiple compartment and Non compartment Pharmacokinetic Models 102 5.1 Multiple compartment models 102 5.2 Non compartmental models 117 5.3 Population pharmacokinetics 121 5.4 Curve fitting and the choice of most appropriate model 122 5.5 Further reading 124 5.6 References 124 6. Kinetics of Metabolism and Excretion 126 6.1 Introduction 126 6.2 Metabolite kinetics 127 6.3 Renal excretion 137 6.4 Excretion in faeces 142 6.5 Further reading 143 6.6 References 144 7. Clearance, Protein Binding and Physiological Modelling 145 7.1 Introduction 145 7.2 Clearance 146 7.3 Physiological modelling 158 7.4 Further reading 161 7.5 References 161 8. Quantitative Pharmacological Relationships 162 8.1 Pharmacokinetics and pharmacodynamics 162 8.2 Concentration effect relationships (dose response curves) 163 8.3 Time dependent models 169 8.4 PK PD modelling 173 8.5 Further reading 177 8.6 References 177 9. Pharmacokinetics of Large Molecules 178 9.1 Introduction 178 9.2 Pharmacokinetics 179 9.3 Plasma kinetics and pharmacodynamics 184 9.4 Examples of particular interest 185 9.5 Further reading 191 9.6 References 191 10. Pharmacogenetics and Pharmacogenomics 192 10.1 Introduction 192 10.2 Methods for the study of pharmacogenetics 193 10.3 N Acetyltransferase 194 10.4 Plasma cholinesterase 197 10.5 Cytochrome P450 polymorphisms 199 10.6 Alcohol dehydrogenase and acetaldehyde dehydrogenase 202 10.7 Thiopurine methyltransferase 202 10.8 Phase 2 enzymes 202 10.9 Transporters 204 10.10 Ethnicity 206 10.11 Pharmacodynamic differences 206 10.12 Personalized medicine 208 10.13 Further reading 209 10.14 References 209 11. Additional Factors Affecting Plasma Concentrations 211 11.1 Introduction 211 11.2 Pharmaceutical factors 213 11.3 Sex 214 11.4 Pregnancy 218 11.5 Weight and obesity 220 11.6 Food, diet and nutrition 225 11.7 Time of day 226 11.8 Posture and exercise 228 11.9 Further reading 231 11.10 References 231 12. Effects of Age and Disease on Drug Disposition 233 12.1 Introduction 233 12.2 Age and development 234 12.3 Effects of disease on drug disposition 242 12.4 Assessing pharmacokinetics in special populations 256 12.5 Further reading 257 12.6 References 258 13. Drug Interactions and Toxicity 260 13.1 Introduction 260 13.2 Drug interactions 261 13.3 Toxicity 273 13.4 Further reading 282 13.5 References 282 14. Perspectives and Prospects: Reflections on the Past, Present and Future of Drug Disposition and Pharmacokinetics 284 14.1 Drug disposition and fate 284 14.2 Pharmacodynamics 286 14.3 Quantification of drugs and pharmacokinetics 286 14.4 The future 289 14.5 Postscript 291 14.6 Further reading 292 14.7 References 292 Appendices 1 Mathematical Concepts and the Trapezoidal Method 293 2 Dye Models to Teach Pharmacokinetics 300 3 Curve Fitting 303 4 Pharmacokinetic Simulations 307 Index 312.
• (source: Nielsen Book Data)9781119261049 20170403

The application of knowledge of drug disposition, and skills in pharmacokinetics, are crucial to the development of new drugs and to a better understanding of how to achieve maximum benefit from existing ones. The book takes the reader from basic concepts to a point where those who wish to will be able to perform pharmacokinetic calculations and be ready to read more advanced texts and research papers. The book will be of benefit to students of medicine, pharmacy, pharmacology, biomedical sciences and veterinary science, including those who have elected to study the topic in more detail, such as via electives and special study modules. It will be of benefit to those involved in drug discovery and development, pharmaceutical and medicinal chemists, as well as budding toxicologists and forensic scientists who require the appropriate knowledge to interpret their findings and as an introductory text for clinical pharmacologists. Early chapters describe the basic principles of the topic while the later ones illustrate the application of those principles to modern approaches to drug development and clinical use. Full colour illustrations facilitate the learning experience and supporting material for course leaders and students can be found on the Companion Web Site.
(source: Nielsen Book Data)9781119261049 20170403

• Interpretive tools
• States of matter
• Thermodynamics
• Physical properties determination
• Nonelectrolytes
• Electrolyte solutions
• Ionic equilibria
• Buffered and isotonic solutions
• Solubility and distribution phenomena
• Complexation and protein binding
• Diffusion
• Biopharmaceutics
• Drug release and dissolution
• Chemical kinetics and stability
• Interfacial phenomena
• Rheology
• Colloidal dispersions & nanotechnology
• Coarse dispersions
• Micromeritics
• Pharmaceutical biotechnology
• Pharmaceutical polymers
• Compounding
• Excipients
• Oral solid dosage forms
• Drug delivery systems and drug product design.

Martin's Physical Pharmacy and Pharmaceutical Sciences is considered the most comprehensive text available on the physical, chemical, and biological principles that underlie pharmacology. This 7th Edition puts a stronger focus on the most essential, practical knowledge, and is updated to reflect the broadening scope and diversity of the pharmaceutical sciences. Whether you're a student, teacher, researcher, or industrial pharmaceutical scientist, this respected textbook and reference will help you apply the elements of biology, physics, and chemistry in your work and study. Master the latest knowledge with brand-new chapters on Excipients and Compounding; revised and expanded coverage of interpretive tools, ionic equilibria, biopharmaceutics, diffusion, drug release and dissolution, and drug delivery systems and drug product design; a renewed focus on physical chemistry; and much more. See how physical chemistry principles apply to practice through abundant examples. Focus on the most need-to-know information via Key Concept boxes..
(source: Nielsen Book Data)9781451191455 20170213

• 1. Selective Effects of Azelaic Acid in Nanovesicles on Cell Lines 2. Photodynamic Antimicrobial Action Based on Nanostructured Photosensitizers 3. Conspectus on Nanotechnology in the Diagnosis and Management of Oral Cancer 4. Lipid-Based Nanocarriers in Cancer Therapy 5. Effect of Polymer-Based Nanoparticles on the Assay of Antimicrobial Drug Delivery Systems 6. Nanometric Biopolymer Devices for Oral Delivery of Macromolecules of Clinical Significance 7. The Use of Nanotechnology in Modern Pharmacotherapy 8. Nanoparticles for Anti-Cancer Drug Delivery "Targeting to Overcome Multiple Drug Resistance" 9. Application Potential of Engineered Liposomes in Tumor Targeting 10. Plant Based Peroral Vaccines 11. Platelet Rich Plasma Incorporated Nanostructures for Tissue Engineering Applications 12. Targeted Nanotherapeutics Based on Cancer Biomarkers 13. Therapeutic Nanoparticles for Targeted Delivery of Anticancer Drugs: State-Of-The-Art and Future Trends 14. Pulmonary Administration of Biodegradable Drug Nanocarriers for More Efficacious Treatment of Fungal Infections in Lungs: Insights Based On Recent Findings 15. Alternative Technologies to Improve Solubility of Ineffectively Water-Soluble Drugs 16. Nanostructures For Tuberculosis Disease Treatment 17. Recombinant Lactic Acid Bacteria Secreting OxdC as a Novel Therapeutic Tool for the Prevention of Kidney Stone Disease.
• (source: Nielsen Book Data)9780323527255 20170612

Multifunctional Systems for Combined Delivery, Biosensing, and Diagnostics explores how multifunctional nanocarriers are being used in combined delivery and diagnostics in contemporary medicine. Particular attention is given to efforts to i) reduce the side effects of therapeutic agents, ii) increase the pharmacological effect, and iii) improve aqueous solubility and chemical stability of different therapeutic agents. The chapters focus on applications of nanostructured materials and nanocarriers, highlighting how these can be used effectively in both diagnosis and delivery. This applied focus makes the book an important reference source for those wanting to learn more about how specific nanomaterials and nanotechnology systems can help to solve drug delivery and diagnostics problems. This book is a valuable resource for materials scientists, bioengineers, and medical researchers who are looking for an applications-oriented guide on how nanotechnology and nanomaterials can be used effectively throughout the medical treatment process, from diagnosis to treatment.
(source: Nielsen Book Data)9780323527255 20170612

• Xanthine Alkaloids: Occurrence, Biosynthesis, and Function in Plants; 1 Introduction; 2 Occurrence of Xanthine Alkaloids in the Plant Kingdom; 2.1 Ericales (Tea and Related Species); 2.2 Gentianales (Coffee and Related Species); 2.3 Aquifoliales (Maté and Related Species); 2.4 Malvales (Cacao, Cola, and Related Species); 2.5 Sapindales (Guaran, Citrus, and Related Plants); 2.6 Other Species; 3 Biosynthesis of Xanthine Alkaloids; 3.1 A Brief History of the Elucidation of the Biosynthesis Pathways; 3.2 Caffeine Biosynthesis Pathways from Xanthosine; 3.2.1 Formation of 7-Methylxanthine

• Feeding ExperimentsEnzyme Studies; Genes and Proteins; 3.2.2 Conversion of 7-Methylxanthine to Caffeine via Theobromine; Feeding Experiments; Enzyme Studies; Genes and Proteins; 3.2.3 Evolutionary Relationship of the Caffeine Synthase Family Proteins; 3.3 Pathways that Supply Xanthosine for Caffeine Biosynthesis; 3.3.1 De Novo Route; 3.3.2 AMP Route; 3.3.3 SAM Cycle Route; 3.3.4 NAD Route; 3.3.5 GMP Route; 3.4 Localization of Xanthine Alkaloid Biosynthesis; 3.4.1 Organs and Tissues; Camellia; Coffea; Theobroma; Maté and Guaran; 3.4.2 Subcellular Accumulation of Xanthine Alkaloids

• 3.4.3 Subcellular Localization of Caffeine Biosynthesis EnzymesCaffeine Synthase; Enzymes Involved in the de Novo Route; Enzymes Involved in the AMP Route; Enzymes Involved in the SAM Route; 3.4.4 Subcellular Localization and Transport of Intermediates; 3.5 Regulation of Caffeine Biosynthesis; 4 Metabolism of Xanthine Alkaloids; 4.1 Methyluric Acid Biosynthesis; 4.2 Biodegradation and Inter-conversion of Xanthine Alkaloids; 4.2.1 The Major Pathway of Caffeine Degradation; 4.2.2 Conventional Purine Catabolic Pathways in Plants; 4.2.3 Diversity of Xanthine Alkaloid Metabolism in Plants; Coffea

• Tea4.2.4 Xanthine Alkaloid Metabolism in Bacteria and Animals; Bacteria; Animals; 5 Ecological Roles of Xanthine Alkaloids; 5.1 Allelopathic Function Theory; 5.1.1 Effect of Xanthine Alkaloids on Germination and Growth of Plants; 5.1.2 Effect of Xanthine Alkaloids on Proliferation of Plant Cells; 5.1.3 Effect of Xanthine Alkaloids on Plant Metabolism; 5.1.4 Effect of Caffeine on Protein Expression Profiles; 5.1.5 Allelopathy in Natural Ecosystems; 5.2 Chemical Defense Theory; 5.2.1 Chemical Defense Against Microorganisms and Animals

• 5.2.2 Proof of the Chemical Defense Theory Demonstrated with Transgenic Plants6 Biotechnology of Xanthine Alkaloids; 6.1 Decaffeinated Coffee and Tea Plants; 6.2 Caffeine-Producing Transgenic Plants; 6.2.1 Antiherbivore Activity; 6.2.2 Antipathogen Activity; 7 Summary and Perspectives; References; The Iboga Alkaloids; 1 Introduction; 2 Biosynthesis; 3 Structural Elucidation and Reactivity; 4 New Molecules; 4.1 Monomers; 4.1.1 Ibogamine and Coronaridine Derivatives; 4.1.2 3-Alkyl- or 3-Oxo-ibogamine/-coronaridine Derivatives; 4.1.3 5- and/or 6-Oxo-ibogamine/-coronaridine Derivatives

• Chapter 1. Traditional Chinese Medicine: Current State, Challenges, and Applications Chapter 2. Serum Pharmacochemistry of Traditional Chinese Medicine: Historical Development and Strategies Chapter 3. Integrated Serum Pharmacochemistry of TCM and Metabolomics Strategies for Innovative Drug Discovery Chapter 4. UPLC/MS and Its Potential in Traditional Chinese Medicine Development Chapter 5. Analytical Characterization of Yin-Chen-Hao-Tang by Serum Pharmacochemistry of TCM Chapter 6. Pharmacokinetic Strategy for Screening the Effective Components From YCHT Chapter 7. Synergism Effects of Active Ingredients From YCHT Chapter 8. Serum Pharmacochemistry of TCM for Screening the Active Ingredients From Wen-Xin Formulae Chapter 9. Characterization and Pharmacokinetic Study of Multiple Constituents From Shengmai San Chapter 10. Multivariate Data Processing Tools to Screen the Active Ingredients From Kai-Xin-San Chapter 11. Serum Pharmacochemistry of TCM for Determining the Active Ingredients of Shuanghuanglian Formulae Chapter 12. Pharmacokinetic-Pharmacodynamic Study of Zhi Zhu Wan Chapter 13. Identification of the Absorbed Components of Shaoyao-Gancao Decoction Chapter 14. Rapid Analysis of Multiple Constituents of Suanzaoren Decoction by UPLC-MS Chapter 15. UPLC-MS Analysis of the Chemical Constituents of Liuwei Dihuang Wan Chapter 16. Multivariate Data Analysis for Rapid Identification of Chemical Constituents of Simiao Wan Chapter 17. Time-Course Study of Multicomponents After Oral Administration of Stemonae Radix Chapter 18. Global Characterization of Chemical Constituents of Phellodendri amurensis Cortex Chapter 19. Comparative Analysis of Chemical Constituents of Phellodendri amurensis Cortex and Zhibai Dihuang Pill Chapter 20. UPLC-MS Determining the Active Ingredients of Herbal Fructus Corni In Vivo Chapter 21. Serum Pharmacochemistry of TCM Screening the Bioactive Components From Moutan Cortex Chapter 22. Rapid Analysis of Constituents and Metabolites From Extracts of Acanthopanax senticosus Harms Leaf Chapter 23. Systematic Characterization of the Absorbed Components of Acanthopanax senticosus Stem Chapter 24. Identification of the Absorbed Constituents of Schisandra Lignans by Serum Pharmacochemistry of TCM.
• (source: Nielsen Book Data)9780128111475 20170313

Serum Pharmacochemistry of Traditional Chinese Medicine: Technologies, Strategies and Applications provides a valuable and indispensable guide on the latest methods, research advances, and applications in this area. Chapters offer cutting-edge information on pharmacokinetics and pharmacodynamics, analytical chemistry, traditional medicine, natural products, bioinformatics, new technologies, therapeutic applications, and more. For researchers and students in academia and industry, this book provides a hands-on description of experimental techniques, along with beneficial guidelines to help advance research in the fields of Traditional Chinese Medicine and drug development.
(source: Nielsen Book Data)9780128111475 20170313

• Preface XIII List of Contributors XVII Part I HDAC Inhibitor Anticancer Drug Discovery 1 1 From DMSO to the Anticancer Compound SAHA, an Unusual Intellectual Pathway for Drug Design 3Ronald Breslow 1.1 Introduction 3 1.2 The Discovery of SAHA (vorinostat) 4 1.3 Clinical Trials 7 1.4 Follow-On Research - Selective HDAC Inhibitors 8 1.5 Conclusion 9 References 9 2 Romidepsin and the Zinc-Binding Thiol Family of Natural Product HDAC Inhibitors 13A. Ganesan 2.1 Histone Deacetylases as a Therapeutic Target 13 2.2 The Discovery and Development of Romidepsin 15 2.3 The Zinc-BindingThiol Family of Natural Product HDAC Inhibitors 18 2.4 Synthetic Analogues of the Zinc-BindingThiol Natural Products 21 2.5 Summary 23 References 24 3 The Discovery and Development of Belinostat 31Paul W. Finn, Einars Loza and Elisabeth Carstensen 3.1 Introduction 31 3.2 Discovery of Belinostat 32 3.2.1 Design Strategy 32 3.2.2 Medicinal Chemistry and SAR 34 3.3 Belinostat Biological Profiling 41 3.3.1 Mode of Action and HDAC Isoform Selectivity 41 3.3.2 Antiproliferative and Antitumor Activity 42 3.4 Formulation Development 44 3.5 Clinical Development 45 3.5.1 Clinical Studies Leading to Approval and Other Clinical Investigations 45 3.5.2 Pharmacokinetics 49 3.5.3 Safety and Tolerability 51 3.6 Conclusions 52 References 53 4 Discovery and Development of Farydak (NVP-LBH589, Panobinostat) as an Anticancer Drug 59Peter Atadja and Lawrence Perez 4.1 Target Identification: From p21Waf1 Induction to HDAC Inhibition 59 4.2 Program Flowchart Assays for Drug Discovery 61 4.3 Hit-To-Lead Campaign: Trichostatin A to LAK974 63 4.4 Lead Optimization: LAK974 to LAQ824 64 4.5 Profiling LAQ824 for Cancer Therapy 66 4.6 Preclinical Development of LAQ824 70 4.7 LAQ824 Follow-Up 72 4.8 Discovery of LBH589 73 4.9 Safety Profile for LBH589 74 4.10 Pan-HDAC Inhibition by LBH589 76 4.11 Cancer Cell-Specific Cytotoxicity of LBH589 76 4.11.1 Toxicity and Safety Studies with LBH589 78 4.11.2 Early Clinical Activity of LBH589 in CTCL 78 4.11.3 Large-Scale Cell Line Profiling to Discover Lineage-Specific LBH589-Sensitive Cancer Indications 79 4.11.4 Clinical Profiling ofHemeMalignancies for LBH589Activity 80 4.11.5 Phase II Study of Oral Panobinostat in Hodgkin Lymphoma 81 4.11.6 Phase IB Clinical Studies in MultipleMyeloma 82 4.11.7 Phase III Registration Study inRelapsed orRefractoryMyeloma 82 4.11.8 Conclusion and Future Perspective 83 References 85 5 Discovery and Development of HDAC Subtype Selective Inhibitor Chidamide: Potential Immunomodulatory Activity Against Cancers 89Xian-Ping Lu, Zhi-Qiang Ning, Zhi-Bin Li, De-Si Pan, Song Shan, Xia Guo, Hai-Xiang Cao, Jin-Di Yu and Qian-Jiao Yang 5.1 Introduction 89 5.1.1 Epigenetics and Cancer 89 5.1.2 Epigenetic Drugs 90 5.2 Discovery of Chidamide 93 5.2.1 Identification of Chemical Scaffold 93 5.2.2 Design and ScreeningNewSelective BenzamideHDACInhibitors 93 5.2.3 Molecular Docking of Chidamide with HDAC2 95 5.3 Molecular Mechanisms of Chidamide 97 5.3.1 Selectivity 97 5.3.2 Induction of Cell Cycle Arrest, Apoptosis and Differentiation of Tumour Cells 98 5.3.3 Reversal of Epithelial toMesenchymal Transition 99 5.3.4 Stimulation of Innate andAntigen-SpecificAntitumour Immunity 99 5.3.5 Multiplicity of Anticancer Mechanisms by Chidamide 100 5.4 Animal Studies 101 5.5 Clinical Development 101 5.5.1 Pharmacokinetics and Pharmacodynamics 101 5.5.2 Unmet Medical Needs for PeripheralT-Cell Lymphoma (PTCL) 102 5.5.3 Efficacy Assessment of Chidamide in PTCL Patients 103 5.5.4 Safety Profile 105 5.6 Future Perspective 106 References 108 Part II Steroidal CYP17 Inhibitor Anticancer Drug Discovery 115 6 Abiraterone Acetate (Zytiga): AnInhibitor of CYP17 as a Therapeutic for Castration-Resistant Prostate Cancer 117Gabriel M. Belfort, Boyd L. Harrisonand Gabriel Martinez Botella 6.1 Introduction 117 6.2 Discovery and Structure-Activity Relationships (SAR) 119 6.3 Preclinical Characterisation of Abiraterone and Abiraterone Acetate 126 6.3.1 Pharmacology 126 6.3.2 Pharmacokinetics 127 6.3.3 Toxicology 128 6.4 Physical Characterisation 129 6.5 Clinical Studies 129 6.6 Conclusion 132 References 133 Part III Anti-Infective Drug Discoveries 137 7 Discovery of Delamanid for the Treatment of Multidrug-Resistant Pulmonary Tuberculosis 139Hidetsugu Tsubouchi, Hirofumi Sasaki, Hiroshi Ishikawa and Makoto Matsumoto 7.1 Introduction 139 7.2 Synthesis Strategy 140 7.3 Synthesis Route 142 7.4 Screening Evaluations 145 7.4.1 Screening Procedure 145 7.4.2 Screening Results 146 7.4.3 Selection of a Compound Candidate for Preclinical Tests 151 7.5 Preclinical Data of Delamanid 151 7.5.1 Antituberculosis Activity 151 7.5.2 Mechanism of Action 153 7.5.3 Pharmacokinetics 153 7.5.4 Genotoxicity and Carcinogenicity 154 7.5.5 Preclinical Therapeutic Efficacy 154 7.6 Clinical Data of Delamanid 155 7.6.1 Clinical Pharmacokinetics 155 7.6.2 Drug-Drug Interactions 156 7.6.3 Cardiovascular Safety 156 7.6.4 Clinical Therapeutic Efficacy 156 7.6.5 Other Clinical Trials 157 7.7 Future Priorities and Conclusion 158 References 159 8 Sofosbuvir: The Discovery of a Curative Therapy for the Treatment of Hepatitis C Virus 163Michael J. Sofia 8.1 Introduction 163 8.2 Discussion 165 8.2.1 Target Rationale: HCVNS5BRNA-Dependent RNA Polymerase 165 8.2.2 Rationale andDesign of a Liver Targeted Nucleotide Prodrug 168 8.2.3 Prodrug Optimization and Preclinical Evaluation 171 8.2.4 Prodrug Metabolism 175 8.2.5 Clinical Proof of Concept of a Liver Targeted Nucleotide Prodrug 176 8.2.6 The Single Diastereomer: Sofosbuvir 176 8.2.7 Sofosbuvir Preclinical Profile 177 8.2.8 Sofosbuvir Clinical Studies 179 8.2.9 Viral Resistance 182 8.3 Conclusion 183 References 184 Part IV Central Nervous System (CNS) Drug Discovery 189 9 The Discovery of the Antidepressant Vortioxetine and the Research that Uncovered Its Potential to Treat the Cognitive Dysfunction Associated with Depression 191Benny Bang-Andersen, Christina Kurre Olsen and Connie Sanchez 9.1 Introduction 191 9.2 The Discovery of Vortioxetine 192 9.3 Clinical Development of Vortioxetine for theTreatment ofMDD 200 9.4 UncoveringVortioxetine's Potential toTreat Cognitive Dysfunction in Patients with MDD 201 9.4.1 Early Preclinical Evidence that Differentiated Vortioxetine from Other Antidepressants 201 9.4.2 Vortioxetine's Primary Targets and Their Putative Impact on Cognitive Function - Early Preclinical Data 202 9.4.3 Hypothesis-Generating Clinical Study of Vortioxetine's Effects on Cognitive Symptoms in Elderly Patients with MDD 203 9.4.4 Substantiation of a Mechanistic Rationale for the Procognitive Effects of Vortioxetine in Preclinical Models and Its Differentiation from SSRIs and SNRIs 204 9.4.5 Confirmation of the Cognitive Benefits of Vortioxetine in Two Large Placebo-Controlled Studies in Adults with MDD 205 9.4.6 Additional Translational Evidence of the Effect of Vortioxetine on Brain Activity During Cognitive Performance 208 9.5 Conclusion 208 References 210 Part V Antiulcer Drug Discovery 215 10 Discovery of Vonoprazan Fumarate (TAK-438) as a Novel, Potent and Long-Lasting Potassium-Competitive Acid Blocker 217Haruyuki Nishida 10.1 Introduction 217 10.2 Limitations of PPIs and the Possibility of P-CABs 218 10.3 Exploration of Seed Compounds 220 10.4 Lead Generation from HTS Hit Compound 1 220 10.5 Analysis of SAR and Structure-Toxicity Relationship for Lead Optimization 223 10.6 Selection of Vonoprazan Fumarate (TAK-438) as a Candidate Compound 224 10.7 Preclinical Study of TAK-438 226 10.8 Clinical Study of TAK-438 228 10.9 Discussion 229 10.10 Conclusion 230 References 232 Part VI Cross-Therapeutic Drug Discovery (Respiratory Diseases/Anticancer) 235 11 Discovery and Development of Nintedanib: A Novel Antiangiogenic and Antifibrotic Agent 237Gerald J. Roth, Rudolf Binder, Florian Colbatzky, Claudia Dallinger, Rozsa Schlenker-Herceg, Frank Hilberg, Lutz Wollin, John Park, Alexander Pautsch and Rolf Kaiser 11.1 Introduction 237 11.2 Structure-Activity Relationships of Oxindole Kinase Inhibitors and the Discovery of Nintedanib 238 11.3 Structural Research 244 11.4 Preclinical Pharmacodynamic Exploration 246 11.4.1 Kinase Inhibition Profile of Nintedanib 246 11.4.2 Oncology, Disease Pathogenesis and Mechanism of Action 246 11.4.3 Idiopathic Pulmonary Fibrosis, Disease Pathogenesis andMechanism of Action 249 11.5 Nonclinical Drug Metabolism and Pharmacokinetics 250 11.6 Clinical Pharmacokinetics 251 11.7 Toxicology 252 11.8 Phase III Clinical Data 253 11.8.1 Efficacy and Safety of Nintedanib in IPF 253 11.8.2 Efficacy and Safety of Nintedanib in NSCLC 255 11.9 Other Oncology Studies 256 11.10 Conclusions 257 References 258 Index 267.
• (source: Nielsen Book Data)9783527800346 20170313

• 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.
• (source: Nielsen Book Data)9783527800322 20170313

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.
(source: Nielsen Book Data)9783527800346 20170313

• Taste receptor gene expression outside the gustatory system.- Medicinal Chemistry of Plant Naturals as Agonists/Antagonists for Taste Receptors.- Chemical activation of TRP channels in taste and smell.- Olfactory transduction channels and their modulation by varieties of volatile substances.- Chemosensory G protein-coupled receptors (GPCR) in blood leukocytes.- Neuronal functions and emerging pharmacology of TAAR1.
• (source: Nielsen Book Data)9783319489254 20170502

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.
(source: Nielsen Book Data)9783319489254 20170502

"The structural complexity and the synthetic challenges facing glycans have historically hampered efforts to study their multifaceted roles and the application of carbohydrates in drug development. However, in very recent years, new synthetic techniques flanked by the growing knowledge about carbohydrate involvement in physiological and pathological states has spurred renewed interest in the chemistry, biology and therapeutic potentialities of carbohydrates. This book offers an overview of key aspects of carbohydrate biology and chemistry that are fundamental for the design of novel therapeutics. The four-part structure of this book introduces these essential components to life, starting from their structure and biological roles and covering analytical methods and synthesis which pave the way for the development of a wide range of therapeutic applications. Leading experts from around the world are brought together to offer their recent research with the ultimate aim of enlightening the reader on the complex yet exciting field of carbohydrate chemistry. Academic and industrial researchers in structural biology, drug discovery and carbohydrate chemistry will find this book an essential guide to the latest research and future potential of medicinal chemistry."-- Provided by publisher.

• Introduction.- Antibiotic resistance development.- Major classes of antibiotics.- Relevant concepts in Biochemistry.- The cell wall as a target.- Mechanism of resistance to B-lactams.- Antibiotic Vancomycin.- Antibiotics that inhibit nucleotide synthesis.- Antibiotics that inhibit DNA synthesis.- Drugs that cause DNA cleavage.- Antibiotics that inhibit RNA synthesis.- Antibiotics that inhibit RNA synthesis.- Antibiotics that disrupt membrane structure.
• (source: Nielsen Book Data)9783319407449 20161010

This textbook discusses how the various types of antibiotics and related drugs work to cure infections. Then it delves into the very serious matter of how bacteria are becoming resistant to these antibiotics. Appropriate for a one-semester course at either the graduate or advanced undergraduate level, this textbook contains worked examples of (1) experimental procedures and (2) interpreting data.
(source: Nielsen Book Data)9783319407449 20161010

• Preface Overview and Recent Advances in QSAR Studies-- Rahul P. Gangwal, Mangesh V. Damre, and Abhay T. Sangamwar Software and Web Resources for Computer-Aided Molecular Modeling and Drug Discovery-- Dharmendra Kumar Yadav, Reeta Rai, Ramendra Pratap, and Harpreet Singh The Rm2 Metrics for Validation of QSAR/QSPR Models-- Kunal Roy and Supratik Kar Considering the Molecular Conformational Flexibility in QSAR Studies-- Javier Garcia, Pablo R. Duchowicz, and Eduardo A. Castro Practical Aspects of Building, Validation and Application of 3D-Pharmacophore Models-- Elumalai Pavadai and Kelly Chibale Application of Conceptual Density Functional Theory in Developing QSAR Models and Their Usefulness in the Prediction of Biological Activity and Toxicity of Molecules-- Sudip Pan, Ashutosh Gupta, Debesh R. Roy, Rajesh K. Sharma, Venkatesan Subramanian, Analava Mitra, and Pratim K. Chattaraj Synopsis of Chemometric Applications to Model PPAR Agonism-- Theodosia Vallianatou, George Lambrinidis, and Anna Tsantili-Kakoulidou Antimicrobial and Immunosuppressive Activitites of Cyclopeptides as Targets for Medicinal Chemistry-- Alicia B. Pomilio, Stella M. Battistaand, and Arturo A. Vitale On the Use of Quantitative Structure Activity Relationships (QSAR) and Global Reactivity Descriptors to Study the Biological Activities of Polychlorinated Biphenyls (PCBs)-- Nazmul Islam Applications of Quantitative Structure-Relative Sweetness Relationships in Food Chemistry-- Cristian Rojas, Pablo R. Duchowicz, Reinaldo Pis Diez, and Piercosimo Tripaldi QSAR Studies of 1, 4-Benzodiazepines as CCKA Antagonist-- Sumitra Nain, P. M. Shivakumar, and Sarvesh Paliwal Docking-Based Scoring Parameters Based QSAR Modeling on a Dataset of Bisphenylbenzimidazole as Non-Nucleoside Reverse Transcriptase Inhibitor-- Surendra Kumar and Meena Tiwari Potential Anti-Inflammatory and Anti-Proliferative Agents.-1h-Isochromen-1-Ones and Their Thio Analogues and Their QSAR Studies-- F. Nawaz Khan, Ponnurengam Malliappan Sivakumar, Mukesh Doble, P. Manivel, and Euh Duck Jeong QSAR Studies on Dihydrofolate Reductase Enzyme: From Model to Biological Activity-- Rajesh Rengarajan, Garima Mathur, Anu Sharma, P. M. Shivakumar, and Sumitra Nain Index.
• (source: Nielsen Book Data)9781771881135 20160919

This important new book provides innovative material, including peer-reviewed chapters and survey articles on new applied research and development, in the scientifically important field of QSAR in medicinal chemistry. QSAR is a growing field because available computing power is continuously increasing, QSAR's potential is enormous, limited only by the quantity and quality of the available experimental input, which are also continuously improving. The number of possible structures for the design of new organic compounds is difficult to imagine, and QSAR helps to predict their activities even before synthesis. The book provides a wealth of valuable information and: * Presents an overview of recent developments in QSAR methodologies along with a brief history of QSAR * Covers the available web resource tools and in silico techniques used in virtual screening and drug discovery processes, compiling an extensive review of web resources in the following categories: databases related to chemical compounds, drug targets, and ADME/toxicity prediction; molecular modeling and drug designing; virtual screening; pharmacophore generation; molecular descriptor calculation software; software for quantum mechanics; ligand binding affinities (docking); and software related to ADME/toxicity prediction * Reviews the rm2 as a more stringent measure for the assessment of model predictivity compared to traditional validation metrics, being specifically important since validation is a crucial step in any QSAR study * Presents linear model improvement techniques that take into account the conformation flexibility of the modeled molecules * Summarizes the building processes of four different pharmacophore models: common-feature, 3D-QSAR, protein-, and protein-ligand complexes * Shows the role of different conceptual density functional theory based chemical reactivity descriptors, such as hardness, electrophilicity, net electrophilicity, and philicity in the design of different QSAR/QSPR/QSTR models * Reviews the use of chemometrics in PPAR research highlighting its substantial contribution in identifying essential structural characteristics and understanding the mechanism of action * Presents the structures and QSARs of antimicrobial and immunosuppressive cyclopeptides, discussing the balance of antimicrobial and haemolytic activities for designing new antimicrobial cyclic peptides * Shows the relationship between DFT global descriptors and experimental toxicity of a selected group of polychlorinated biphenyls, exploring the efficacy of three DFT descriptors * Reviews the applications of Quantitative Structure-Relative Sweetness Relationships (QSRSR), showing that the last decade was marked by an increase in the number of studies regarding QSAR applications for both understanding the sweetness mechanism and synthesizing novel sweetener compounds for the food additive industry The wide coverage makes this book an excellent reference for those in chemistry, pharmacology, and medicine as well as for research centers, governmental organizations, pharmaceutical companies, and health and environmental control organizations.
(source: Nielsen Book Data)9781771881135 20160919

• Synthesis of a Potent NAE Inhibitor: Pevonedistat / Mizutani, Hirotaki; Langston, Steven; Vyskocil, Stepan / <a href="http://dx.doi.org/10.1021/bk-2016-1240.ch001 --">http://dx.doi.org/10.1021/bk-2016-1240.ch001 --</a> Process Development and GMP Production of a Potent NEDD8-Activating Enzyme (NAE) Inhibitor: Pevonedistat / Armitage, Ian; McCarron, Ashley; Zhu, Lei / <a href="http://dx.doi.org/10.1021/bk-2016-1240.ch002 --">http://dx.doi.org/10.1021/bk-2016-1240.ch002 --</a> The Discovery and Synthesis of the CGRP Receptor Antagonist MK-3207 / Bell, Ian M., Department of Discovery Chemistry, Merck & Co., Inc., 770 Sumneytown Pike, West Point, Pennsylvania 19486, United States; Bulger, Paul G., Department of Process Research & Development, Merck & Co., Inc., 126 East Lincoln Avenue, Rahway, New Jersey 07065, United States; McLaughlin, Mark, Department of Process Research & Development, Merck & Co., Inc., 126 East Lincoln Avenue, Rahway, New Jersey 07065, United States / <a href="http://dx.doi.org/10.1021/bk-2016-1240.ch003 --">http://dx.doi.org/10.1021/bk-2016-1240.ch003 --</a> Design and Enabling Development of Hydroxyethylamine-Derived BACE1 Inhibitor / Tedrow, Jason S., Process Development, Amgen Inc, One Amgen Center Drive, Thousand Oaks, California 91320, United States; Zhong, Wenge, Discovery Research, Amgen Asia R&D Center, 99 Haike Road, 4th Floor, Building 6, Shanghai 201210, P. R. China / <a href="http://dx.doi.org/10.1021/bk-2016-1240.ch004 --">http://dx.doi.org/10.1021/bk-2016-1240.ch004 --</a> Identification and Optimization of a Series of Non-Steroidal Trifluoromethylcarbinol Glucocorticoid Receptor Agonists / Harcken, Christian, Department of Immunology and Respiratory Discovery Research, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, Connecticut 06778, United States; Razavi, Hossein, Department of Small Molecule Discovery Research, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, Connecticut 06778, United States / <a href="http://dx.doi.org/10.1021/bk-2016-1240.ch005 --">http://dx.doi.org/10.1021/bk-2016-1240.ch005 --</a> Development of an Asymmetric Route for Large-Scale Synthesis of a Glucocorticoid Agonist / Reeves, Jonathan T.; Fandrick, Daniel R.; Song, Jinhua J.; Tan, Zhulin; Kim, Soojin; Yang, Bing-Shiou; Yee, Nathan K.; Senanayake, Chris H. / <a href="http://dx.doi.org/10.1021/bk-2016-1240.ch006 --">http://dx.doi.org/10.1021/bk-2016-1240.ch006 --</a> The Medicinal Chemistry and Commercial Manufacturing Behind the Discovery and Development of the Hedgehog Inhibitor Vismodegib / Angelaud, Remy, Small Molecule Process Chemistry, Genentech, A Member of the Roche Group, 1 DNA Way, South San Francisco, California 94080, United States; Sutherlin, Daniel P., Discovery Chemistry, Genentech, A Member of the Roche Group, 1 DNA Way, South San Francisco, California 94080, United States; Reynolds, Mark, Small Molecule Process Chemistry, Genentech, A Member of the Roche Group, 1 DNA Way, South San Francisco, California 94080, United States; Savage, Scott, Small Molecule Process Chemistry, Genentech, A Member of the Roche Group, 1 DNA Way, South San Francisco, California 94080, United States; Stumpf, Andreas, Small Molecule Process Chemistry, Genentech, A Member of the Roche Group, 1 DNA Way, South San Francisco, California 94080, United States / <a href="http://dx.doi.org/10.1021/bk-2016-1240.ch007 --">http://dx.doi.org/10.1021/bk-2016-1240.ch007 --</a> Discovery and Process Development of Class I PI3K and Class I PI3K/mTOR Inhibitors GDC-0941 and GDC-0980 / Babu, Srinivasan, Small Molecule Process Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States; Gosselin, Francis, Small Molecule Process Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States; Humphries, Theresa, Small Molecule Process Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States; Olivero, Alan, Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States; Sutherlin, Daniel, Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States; Tian, Qingping, Small Molecule Process Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States / <a href="http://dx.doi.org/10.1021/bk-2016-1240.ch008 --">http://dx.doi.org/10.1021/bk-2016-1240.ch008 --</a> The Development and Manufacture of Azacitidine, Decitabine, and Cladribine: Stereoselective Ribonucleoside Drug Synthesis Using the Vorbrüggen Glycosylation / Co, Erick W.; Henschke, Julian P. / <a href="http://dx.doi.org/10.1021/bk-2016-1240.ch009 --">http://dx.doi.org/10.1021/bk-2016-1240.ch009 --</a> Editors’ Biographies / <a href="http://dx.doi.org/10.1021/bk-2016-1240.ot001">http://dx.doi.org/10.1021/bk-2016-1240.ot001</a>

• Computational Pharmaceutical Solid-State Chemistry / Yuriy A Abramov
• Navigating the Solid Form Landscape with Structural Informatics / Peter T A Galek, Elna Pidcock, Peter A Wood, Neil Feeder, Frank H Allen
• Theoretical Hydrogen-Bonding Analysis for Assessment of Physical Stability of Pharmaceutical Solid Forms / Yuriy A Abramov
• Improving Force Field Parameters for Small-Molecule Conformation Generation / Dmitry Lupyan, Yuriy A Abramov, Woody Sherman
• Advances in Crystal Structure Prediction and Applications to Pharmaceutical Materials / Graeme M Day
• Integrating Computational Materials Science Tools in Form and Formulation Design / Joseph F Krzyzaniak, Paul A Meenan, Cheryl L Doherty, Klimentina Pencheva, Suman Luthra, Aurora Cruz-Cabeza
• Current Computational Approaches at Astrazeneca for Solid-State and Property Predictions / Sten O Nilsson Lill, Staffan Schantz, Viktor Broo, Anders Broo
• Synthonic Engineering / Kevin J Roberts, Robert B Hammond, Vasuki Ramachandran, Robert Docherty
• New Developments in Prediction of Solid-State Solubility and Cocrystallization Using COSMO-RS Theory / Christoph Loschen, Andreas Klamt
• Modeling and Prediction of Solid Solubility by GE Models / Larissa P Cunico, Anjan K Tula, Roberta Ceriani, Rafiqul Gani
• Molecular Simulation Methods to Compute Intrinsic Aqueous Solubility of Crystalline Drug-Like Molecules / David S Palmer, Maxim V Fedorov
• Calculation of NMR Tensors / Luís Mafra, Sérgio Santos, Mariana Sardo, Heather Frericks Schmidt
• Molecular Dynamics Simulations of Amorphous Systems / Bradley D Anderson, Tian-Xiang Xiang
• Numerical Simulations of Unit Operations in Pharmaceutical Solid Dose Manufacturing / Ekneet Kaur Sahni, Shivangi Naik, Bodhisattwa Chaudhuri.

• Aims and Objectives
• Materials and Methods
• Development and Validation of High-Throughput Crystallisation and Analysis (HTCAA) Methodology for Physical Form Screening
• Predicting Crystallisability of Organic Molecules Using Statistical Modelling Techniques
• Exploring the Crystal Structure Landscape of Olanzapine
• Exploring the Physical Form Landscape of Clozapine, Amoxapine and Loxapine
• Conclusions and Further Work.

This thesis investigates a range of experimental and computational approaches to the discovery of solid forms. It illustrates an inexpensive, practical and accurate way to predict the crystallizability of organic compounds based on molecular structure alone, while also highlighting the molecular factors that inhibit or promote crystallization. Furthermore, readers will gain a better understanding of the key factors underpinning solid-state structure and diversity. A major part of the thesis highlights experimental work carried out on two structurally very similar compounds, while another main section examines the influence of small changes in structure and substituents on solid-state structure and diversity using computational tools including crystal structure prediction, PIXEL calculations, Xpac, Mercury and statistical modelling tools. In closing, the author presents a fast validated method for solid-state form screening using Raman microscopy on multi-well plates to explore the experimental crystallization space.

Following its successful predecessor, this book covers the fundamentals, delivery routes and vehicles, and practical applications of drug delivery. In the 2nd edition, almost all chapters from the previous are retained and updated and several new chapters added to make a more complete resource and reference. Helps readers understand progress in drug delivery research and applications Updates and expands coverage to reflect advances in materials for delivery vehicles, drug delivery approaches, and therapeutics Covers recent developments including transdermal and mucosal delivery, lymphatic system delivery, theranostics Adds new chapters on nanoparticles, controlled drug release systems, theranostics, protein and peptide drugs, and biologics delivery.
(source: Nielsen Book Data)9781118833360 20170313

• 1. Factors that impact the developability of drug candidates
• 2. Physiological, biochemical, and chemical barriers to oral drug delivery
• 3. Physicochemical properties, formulation, and drug delivery
• 4. Targeted bioavailability: a fresh look at pharmacokinetic and pharmacodynamic issues in drug discovery and development
• 5. The role of transporters in drug delivery and excretion
• 6. Intracellular delivery and disposition of small-molecular-weight drugs
• 7. Cell culture models for drug transport studies
• 8. Intellectural property and regulatory issues in drug delivery research
• 9. Presystemic and first-pass metabolism
• 10. Pulmonary drug delivery: pharmaceutical chemistry and aerosol technology
• 11. Transdermal delivery of drugs using patches and patchless delivery systems
• 12. Prodrug approaches to drug delivery
• 13. Liposomes as drug delivery vehicles
• 14. Nanoparticles as drug delivery vehicles
• 15. Evoluation of controlled drug delivery systems
• 16. Pathways for drug delivery to the central nervous system
• 17. Metabolic activation and drug targeting
• 18. Targeted delivery of drugs to the colon
• 19. Receptor-mediated drug delivery
• 20. Protein and peptide conjugates for targeting therapeutics and diagnostics to specific cells
• 21. Drug delivery to the lymphatic system
• 22. The development of cancer theranostics: a new emerging tool toward personalized medicine
• 23. Intracellular delivery of proteins and peptides
• 24. Vaccine delivery: current routes of administration and novel approaches
• 25. Delivery of genes and oligonucleotides
• Index.

• Front Cover; Drug-Like Properties: Concepts, Structure, Design, and Methods from ADME to Toxicity Optimization; Copyright; Dedication; Contents; Preface; Preface to Second Edition; Preface to First Edition; Chapter 1: Introduction; 1.1. Drug-like Properties in Drug Discovery; 1.2. Purpose of This Book; Problems; References; Chapter 2: Benefits of Property Assessment and Good Drug-Like Properties; 2.1. Introduction; 2.2. Discovery Scientists Optimize Many Properties; 2.3. Introduction to the Drug Discovery and Development Process; 2.4. Benefits of Good Drug-like Properties

• 2.4.1. Reduced Development Attrition2.4.2. More Efficient Drug Discovery; 2.4.3. More Efficient Drug Development; 2.4.4. Higher Patient Compliance; 2.4.5. Improved Biological Research in Drug Discovery; 2.4.6. Enabled Partnerships for Drug Development; 2.4.7. Human Modeling and Clinical Planning; 2.4.8. Balance of Properties and Activity; 2.5. Property Profiling in Drug Discovery; 2.6. Drug-like Property Optimization in Drug Discovery; Problems; References; Chapter 3: In Vivo Environments Affect Drug Exposure; 3.1. Introduction; 3.2. Drug Dosing; 3.3. Stomach

• 3.3.1. Gastric Acidic Degradation3.4. Intestinal Environment; 3.4.1. Dissolution Rate; 3.4.2. Solubility; 3.4.3. Permeability; 3.4.4. Intestinal Metabolism; 3.4.5. Intestinal Enzymatic Hydrolysis; 3.4.6. Absorption Enhancement in the Intestine; 3.5. Bloodstream; 3.5.1. Plasma Enzyme Hydrolysis; 3.5.2. Plasma Protein Binding; 3.5.3. Red Blood Cell Binding; 3.6. Liver; 3.6.1. Permeation into and out of Hepatocytes; 3.6.2. Hepatic Metabolism; 3.6.3. Biliary Extraction; 3.7. Kidney; 3.8. Blood-Tissue Barriers; 3.9. Tissue Distribution; 3.9.1. Nonspecific Binding in Tissue

• 3.10. Consequences of Chirality3.11. Overview of in vivo Challenges to Drug Exposure; Problems; References; Chapter 4: Prediction Rules for Rapid Property Profiling from Structure; 4.1. Introduction; 4.2. General Concepts for Prediction Rules; 4.3. Rule of 5; 4.4. Veber Rules; 4.5. Waring Rules; 4.6. Golden Triangle; 4.7. Other Predictive Rules; 4.8. Application of Rules for Compound Assessment; 4.9. Applications of Predictive Rules; Problems; References; Chapter 5: Lipophilicity; 5.1. Lipophilicity Fundamentals; 5.2. Lipophilicity Effects

• 5.3. Lipophilicity Case Studies and Structure Modification5.3.1. Lipophilicity Modification for Biological Activity; 5.3.2. Lipophilicity Modification for Pharmacokinetics; 5.3.3. Lipophilicity Modification for Toxicity; Problems; References; Chapter 6: pKa; 6.1. pKa Fundamentals; 6.2. pKa Effects; 6.2.1. pKa Affects Efficacy; 6.2.2. pKa Affects Pharmacokinetics; 6.2.3. pKa Affects Toxicity; 6.3. pKa Case Studies; 6.3.1. pKa and Activity Examples; 6.3.2. pKa and Pharmacokinetics Examples; 6.4. Structure Modification Strategies for pKa; Problems; References; Chapter 7: Solubility

Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, only a fraction have sufficient ADME (absorption, distribution, metabolism, elimination) properties, and acceptable toxicology properties, to become a drug product that will successfully complete human Phase I clinical trials. Drug-Like Properties: Concepts, Structure Design and Methods from ADME to Toxicity Optimization, Second Edition, provides scientists and students the background and tools to understand, discover, and develop optimal clinical candidates. This valuable resource explores physiochemical properties, including solubility and permeability, before exploring how compounds are absorbed, distributed, and metabolized safely and stably. Review chapters provide context and underscore the importance of key concepts such as pharmacokinetics, toxicity, the blood-brain barrier, diagnosing drug limitations, prodrugs, and formulation. Building on those foundations, this thoroughly updated revision covers a wide variety of current methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties for process and product improvement. From conducting key assays for interpretation and structural analysis, the reader learns to implement modification methods and improve each ADME property. Through valuable case studies, structure-property relationship descriptions, and structure modification strategies, Drug-Like Properties, Second Edition, offers tools and methods for ADME/Tox scientists through all aspects of drug research, discovery, design, development, and optimization.