1 online resource
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.
ix, 701 pages : illustrations ; 28 cm
  • 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
Science Library (Li and Ma)
1 online resource (xxviii, 506 p.) : ill. (some col.)
"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.
1 online resource (xii, 219 pages) : illustrations (some color) Digital: data file.
  • 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
xxv, 430 pages : illustrations ; 24 cm
  • 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
Science Library (Li and Ma)
1 online resource.
  • 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.
1 online resource (580 pages).
  • 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.
1 online resource
1 online resource (xiv, 779 pages) : illustrations.
  • Dedication; Preface; Contents; Contributors; Chapter 1: Route-Specific Challenges in the Delivery of Poorly Water-Soluble Drugs; 1.1 Introduction; 1.2 Oral Route of Administration; 1.2.1 Challenges in Oral Delivery of Poorly Water-Soluble Drugs; 1.3 Parenteral Route of Administration; 1.3.1 Challenges in Parenteral Delivery of Poorly Water-­Soluble Drugs; 1.4 Ocular Route of Administration; 1.4.1 Challenges in Ocular Delivery of Poorly Water-Soluble Drugs; 1.5 Nasal Route of Administration; 1.5.1 Challenges in Nasal Delivery of Poorly Water-Soluble Drugs; 1.6 Pulmonary Route of Administration
  • 1.6.1 Challenges in Pulmonary Delivery of Poorly Water-­Soluble Drugs1.7 Summary; References; Chapter 2: Optimizing the Formulation of Poorly Water-­Soluble Drugs; 2.1 Introduction; 2.1.1 Solubility Studies; Solubility Prediction; 2.1.2 Experimental Aqueous Solubility Determination; 2.1.3 pH-Solubility Profiles; 2.1.4 Intrinsic Dissolution; Compact Preparation; Intrinsic Dissolution Testing; 2.2 Solid-State Characterization; 2.2.1 Thermal Analysis; Differential Scanning Calorimetry; Flory-Huggins; Thermogravimetric Analysis
  • 2.2.2 Fourier Transform Infrared Spectroscopy2.2.2.1 Sample Preparation; Polymorph Screening; Excipient Interactions; 2.2.3 X-Ray Diffraction; Parameter Selection; Polymorph Screening; Excipient Interactions; Pair Distribution Function (PDF); 2.2.4 Specific Surface Area; BET Surface Area Analysis; 2.2.5 Solid-State Nuclear Magnetic Resonance (SSNMR); 2.2.6 Residual Solvent Analysis; Residual Solvent Guidelines; Analytical Determination of Residual Solvent Levels; 2.3 Stability Testing; 2.3.1 Stability Monitoring
  • 2.3.2 Chemical Stability2.3.3 Stability Testing Conditions; 2.4 Dissolution Testing; 2.4.1 Dissolution Studies; Sample Handling; Excipient Screening for Supersaturation Maintenance Ability; Supersaturation Dissolution Studies; Alternative Dissolution Studies; 2.4.2 In Vivo Testing; Administration Via Inhalation; Oral Administration; 2.5 Conclusions; References; Chapter 3: Solid-State Techniques for Improving Solubility; 3.1 Introduction; 3.2 Pharmaceutical Salts; 3.2.1 Pharmaceutical Salt Selection; 3.2.2 Solubility Enhancement
  • 3.3 Polymorphs and Amorphous Forms3.3.1 Polymorph Preparation; 3.3.2 Amorphous Form Preparation; 3.3.3 Thermodynamics of Metastable Solids; 3.3.4 Solubility and Bioavailability Enhancement; 3.4 Pharmaceutical Co-crystals; 3.4.1 Co-crystal Preparation; 3.4.2 Solubility of Co-crystals; 3.5 Summary; References; Chapter 4: Mechanical Particle-Size Reduction Techniques; 4.1 Introduction; 4.2 Rationale Behind the Reduction of Particle-Size; 4.3 Milling; 4.3.1 Dry Milling; Fluidized Bed Jet Milling; Spiral Jet "Pancake" Mill; Pin Mill
The objective of this volume is to consolidate within a single text the most current knowledge, practical methods, and regulatory considerations pertaining to formulations development with poorly water-soluble molecules. A pharmaceutical scientist's approach toward solubility enhancement of a poorly water-soluble molecule typically includes detailed characterization of the compound's physiochemical properties, solid-state modifications, advanced formulation design, non-conventional process technologies, advanced analytical characterization, and specialized product performance analysis techniques. The scientist must also be aware of the unique regulatory considerations pertaining to the non-conventional approaches often utilized for poorly water-soluble drugs. One faced with the challenge of developing a drug product from a poorly soluble compound must possess at minimum a working knowledge of each of the abovementioned facets and detailed knowledge of most. In light of the magnitude of the growing solubility problem to drug development, this is a significant burden especially when considering that knowledge in most of these areas is relatively new and continues to develop.
1 online resource.
Pharmaceutical manufacturing was one of the first industries to recognize the importance of green chemistry, with pioneering work including green chemistry metrics and alternative solvents and reagents. Today, other topical factors also have to be taken into consideration, such as rapidly depleting resources, high energy costs and new legislation.This book addresses current challenges in modern green chemical technologies and sustainability thinking. It encompasses a broad range of topics covered by the CHEM21 project -- Europe's largest public-private partnership project which aims to develop a toolbox of sustainable technologies for green chemical intermediate manufacture. Divided into two sections, the book first gives an overview of the key green chemistry tools, guidance and considerations aimed at developing greener processes, before moving on to look at cutting-edge synthetic methodologies.Featuring innovative research, this book is an invaluable reference for chemists across academia and industry wanting to further their knowledge and understanding of this important topic.
1 online resource. Digital: text file; PDF.
This book presents efficient and practical methods for the synthesis of various functionalized organic molecules from haloalkynes through different reaction processes such as cross-coupling reactions, nucleophilic additions and cycloadditions. It consists of four chapters demonstrating interesting examples of these transformations, and showcasing the synthetic power of haloalkynes for rapid assembly of complex molecular structures. Most of the protocols allow multiple bond-forming events to occur in a single operation, offering opportunities to advance chemical synthesis and address the increasing demands for green and sustainable chemistry. It also presents a wide range of functionalized products, including many synthetically useful conjugated cyclic and acyclic structures that have potential applications in materials science, chemical biology and natural product synthesis. This book is a valuable reference not only for organic chemists, but also for biologists and materials scientists involved in the modern synthesis of organic compounds and materials. Huanfeng Jiang and Wanqing Wu are both Professors at the School of Chemistry and Chemical Engineering, South China University of Technology, China. Chuanle Zhu is a Postdoctoral Fellow at the School of Chemistry and Chemical Engineering, South China University of Technology, China.
xi, 220 pages : illustrations ; 24 cm.
Science Library (Li and Ma)
xv, 341 pages : illustrations ; 26 cm.
  • Preface xi Contributors xiii PART I. INFECTIOUS DISEASES 1 Chapter 1. Entecavir (Baraclude): A Carbocyclic Nucleoside for the Treatment of Chronic Hepatitis B 3 1 Background 3 2 Pharmacology 5 3 Structure Activity Relationship (SAR) 6 4 Pharmacokinetics and Drug Metabolism 7 5 Efficacy and Safety 8 6 Syntheses 8 7 References 14 Chapter 2. Telaprevir (Incivek) and Boceprevir (Victrelis): NS3/4A Inhibitors for Treatment for Hepatitis C Virus (HCV) 15 1 Background 16 2 Pharmacology 16 3 Structure Activity Relationship (SAR) 17 4 PK and Drug Metabolism 20 5 Efficacy and Safety 22 6 Synthesis 24 7 Conclusions 38 8 References 39 Chapter 3. Daclatasvir (Daklinza): The First-in-Class HCV NS5A Replication Complex Inhibitor 43 1 Background 43 2 Discovery Medicinal Chemistry 45 3 Mode of Action 48 4 Pharmacokinetics and Drug Metabolism 49 5 Efficacy and Safety 49 6 Syntheses 52 7 References 57 Chapter 4. Sofosbuvir (Sovaldi): The First-in-Class HCV NS5B Nucleotide Polymerase Inhibitor 61 1 Background 61 2 Pharmacology 63 3 Structure Activity Relationship (SAR) 64 4 Pharmacokinetics and Drug Metabolism 68 5 Efficacy and Safety 69 6 Syntheses 72 7 Summary 76 8 References 76 Chapter 5. Bedaquiline (Sirturo): A Diarylquinoline that Blocks Tuberculosis ATP Synthase for the Treatment of Multi-Drug Resistant Tuberculosis 81 1 Background 81 2 Pharmacology 84 3 Structure Activity Relationship (SAR) 85 4 Pharmacokinetics and Drug Metabolism 86 5 Efficacy and Safety 87 6 Syntheses 88 7 References 96 PART II. CANCER 99 Chapter 6. Enzalutamide (Xtandi): An Androgen Receptor Antagonist for Late-Stage Prostate Cancer 101 1 Background 101 2 Pharmacology 103 3 Structure Activity Relationship (SAR) 104 4 Pharmacokinetics and Drug Metabolism 108 5 Efficacy and Safety 109 6 Synthesis 111 7 Compounds in Development 114 8 References 115 Chapter 7. Crizotinib (Xalkori): The First-in-Class ALK/ROS Inhibitor for Non-small Cell Lung Cancer 119 1 Background: Non-small Cell Lung Cancer (NSCLC) Treatment 119 2 Discovery Medicinal Chemistry Effort: SAR and Lead Optimization of Compound 2 as a c-Met Inhibitor 120 3 ALK and ROS in Non-small Cell Lung Cancer (NSCLC) Treatment 127 4 Preclinical Model Tumor Growth Inhibition Efficacy and Pharmacology 127 5 Human Clinical Trials 128 6 Introduction to the Synthesis and Limitations of the Discovery Route to Crizotinib Analogs 129 7 Process Chemistry: Initial Improvements 131 8 Process Chemistry: Enabling Route to Crizotinib 135 9 Development of the Commercial Process 141 10 Commercial Synthesis of Crizotinib 147 11 References 152 Chapter 8. Ibrutinib (Imbruvica): The First-in-Class Btk Inhibitor for Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia 157 1 Background 157 2 Pharmacology 159 3 Structure Activity Relationship (SAR) 159 4 Pharmacokinetics and Drug Metabolism 161 5 Efficacy and Safety 161 6 Syntheses 162 7 References 164 Chapter 9. Palbociclib (Ibrance): The First-in-Class CDK4/6 Inhibitor for Breast Cancer 167 1 Background 167 2 Pharmacology 168 3 Discovery Program 169 4 Preclinical Profile of Palbociclib 175 5 Clinical Profile of Palbociclib 176 6 Early Process Development for Palbociclib 177 7 Commercial Process for Preparation of Palbociclib 192 8 References 193 PART III. CARDIOVASCULAR DISEASES 197 Chapter 10. Ticagrelor (Brilinta) and Dabigatran Etexilate (Pradaxa): P2Y12 Platelet Inhibitors as Anti-coagulants 199 1 Introduction 200 2 Dabigatran Etexilate 200 3 Ticagrelor 207 4 The Future 219 5 References 220 PART IV. CNS DRUGS 223 Chapter 11. Suvorexant (BELSOMRA): The First-in-Class Orexin Antagonist for Insomnia 225 1 Background 225 2 Pharmacology 229 3 Pharmacokinetics and Drug Metabolism 230 4 Efficacy and Safety 231 5 Structure Activity Relationship (SAR) 231 6 Synthesis 233 7 References 239 Chapter 12. Lorcaserin (Belviq): Serotonin 2C Receptor Agonist for the Treatment of Obesity 243 1 Background 243 2 Pharmacology 245 3 Structure Activity Relationship (SAR) 246 4 Pharmacokinetics and Drug Metabolism 248 5 Efficacy and Safety 249 6 Synthesis 250 7 References 253 Chapter 13. Fingolimod (Gilenya): The First Oral Treatment for Multiple Sclerosis 255 1 Background 255 2 Structure Activity Relationship (SAR) 257 3 Pharmacology 259 4 Human Pharmacokinetics and Drug Metabolism 260 5 Efficacy and Safety 261 6 Syntheses 263 7 Summary 268 8 References 269 Chapter 14. Perampanel (Fycompa): AMPA Receptor Antagonist for the Treatment of Seizure 271 1 Background 271 2 Pharmacology 273 3 Structure Activity Relationship (SAR) 274 4 Pharmacokinetics and Drug Metabolism 276 5 Efficacy and Safety 277 6 Syntheses 278 7 References 280 PART V. ANTI-INFLAMMATORY DRUGS 283 Chapter 15. Tofacitinib (Xeljanz): The First-in-Class JAK Inhibitor for the Treatment of Rheumatoid Arthritis 285 1 Background 285 2 Structure Activity Relationships (SAR) 287 3 Safety, Pharmacology and Pharmacokinetics 289 4 Syntheses 290 5 Development of the Commercial Manufacturing Process 292 6 References 300 PART VI. MISCELLANEOUS DRUGS 303 Chapter 16. Ivacaftor (Kalydeco): A CFTR Potentiator for the Treatment of Cystic Fibrosis 305 1 Background 305 2 Pharmacology 306 3 Structure Activity Relationship (SAR) 307 4 Pharmacokinetics and Drug Metabolism 308 5 Efficacy and Safety 310 6 Syntheses 311 7 References 315 Chapter 17. Febuxostat (Uloric): A Xanthine Oxidase Inhibitor for the Treatment of Gout 317 1 Background 317 2 Pharmacology 319 3 Structure Activity Relationship (SAR) 320 4 Pharmacokinetics and Drug Metabolism 321 5 Efficacy and Safety 322 6 Syntheses 323 7 Drug in Development: Lesinurad Sodium 328 8 References 330 Index 331.
  • (source: Nielsen Book Data)9781118820056 20160619
This book covers all aspects of the medicinal chemistry of the latest drugs, and the cutting-edge science associated with them. Following the editors 3 successful drug synthesis books, this provides expert analysis of the pros and cons of different synthetic routes and demystifies the process of modern drug discovery for practitioners and researchers. * Summarizes for each drug: respective disease area, important properties and SAR (structure-activity relationship), and chemical synthesis routes / options * Includes case studies in each chapter * Illustrates how chemistry, biology, pharmacokinetics, and a host of disciplines come together to produce successful medicines * Explains the advantages of process synthesis versus the synthetic route for drug discovery.
(source: Nielsen Book Data)9781118820056 20160619
Science Library (Li and Ma)
1 online resource (x, 263 p.) : ill. (some color). Digital: text file; PDF.
  • Nanostructured systems for fluorescence imaging applications.- Luminescent silica nanoparticles for optical imaging.- Gold-based nanomaterials for applications in nanomedicine.- Core-shell polymer nanoparticles for photodynamic therapy of cancer.- Photoactivable surfaces for biomedical applications.- Up-converting nanoparticles for drug delivery.- Quantum dots for biomedical applications.- Engineered nanoconstructs for multimodal phototherapy.
  • (source: Nielsen Book Data)9783319229416 20160619
The series Topics in Current Chemistry presents critical reviews of the present and future trends in modern chemical research. The scope of coverage is all areas of chemical science including the interfaces with related disciplines such as biology, medicine and materials science. The goal of each thematic volume is to give the non-specialist reader, whether in academia or industry, a comprehensive insight into an area where new research is emerging which is of interest to a larger scientific audience. Each review within the volume critically surveys one aspect of that topic and places it within the context of the volume as a whole. The most significant developments of the last 5 to 10 years are presented using selected examples to illustrate the principles discussed. The coverage is not intended to be an exhaustive summary of the field or include large quantities of data, but should rather be conceptual, concentrating on the methodological thinking that will allow the non-specialist reader to understand the information presented. Contributions also offer an outlook on potential future developments in the field. Review articles for the individual volumes are invited by the volume editors. Readership: research chemists at universities or in industry, graduate students.
(source: Nielsen Book Data)9783319229416 20160619
1 online resource (v, 252 pages)
1 online resource.
  • Solar water splitting using semiconductor photocatalyst powder.- Co-catalysts for water splitting.- CO2 reduction to hydrocarbons.- Biomimetic water oxidation systems.- Plasmon assisted solar energy conversion.- Heterojunctions in composite photocatalysts.- Physical limits of solar energy conversion in the Earth system.- Nanomaterial Catalysts for Water Photoelectrolysis.- Solar water splitting using photoelectrochemical cells.- Principle of natural photosynthesis.-Advanced and in-situ characterization techniques.- Perspectives.
  • (source: Nielsen Book Data)9783319230986 20160815
The series Topics in Current Chemistry presents critical reviews of the present and future trends in modern chemical research. The scope of coverage is all areas of chemical science including the interfaces with related disciplines such as biology, medicine and materials science. The goal of each thematic volume is to give the non-specialist reader, whether in academia or industry, a comprehensive insight into an area where new research is emerging which is of interest to a larger scientific audience. Each review within the volume critically surveys one aspect of that topic and places it within the context of the volume as a whole. The most significant developments of the last 5 to 10 years are presented using selected examples to illustrate the principles discussed. The coverage is not intended to be an exhaustive summary of the field or include large quantities of data, but should rather be conceptual, concentrating on the methodological thinking that will allow the non-specialist reader to understand the information presented. Contributions also offer an outlook on potential future developments in the field. Review articles for the individual volumes are invited by the volume editors. Readership: research chemists at universities or in industry, graduate students.
(source: Nielsen Book Data)9783319230986 20160815
1 online resource.
  • Introduction.- Ring-Opening Reactions of Aminocyclopropanes.- Synthesis and [4+2] Annulation of Aminocyclobutanes.- Conclusions and Outlook.- Experimental Part.
  • (source: Nielsen Book Data)9783319230054 20160619
This thesis presents a general approach to accessing nitrogen-substituted hetero- and carbocycles. In short, the annulation reactions developed in the thesis make it possible to access nitrogen-substituted four-, five- and six-membered rings, all essential building blocks for the synthesis of bioactive molecules. Many natural products display a saturated polycyclic core allowing a well-defined arrangement of functional groups in space. As such, they can interact with biological targets with a high degree of affinity and selectivity, surpassing many synthetic drugs. Nevertheless, the efficient synthesis of such complex ring systems poses a challenge for organic chemistry. Through careful tuning of the electronic properties of a nitrogen donor group and a diester acceptor group, the first [3+2] annulation reaction between aminocyclopropanes and enol ethers or carbonyl compounds is now possible. The reaction proceeded under mild catalytic conditions, and the building blocks obtained can be found at the core of bioactive alkaloids, drugs such as Ramipril and biomolecules such as DNA and RNA. Thanks to the dynamic kinetic asymmetric annulation of aminocyclopropanes with enol ethers and aldehydes, access to enantioenriched compounds is also now possible. Lastly, a synthesis of donor-acceptor aminocyclobutanes via [2+2] cycloaddition using a cheap iron catalyst was developed, allowing them to be used in [4+2] annulations to access cyclohexylamines.
(source: Nielsen Book Data)9783319230054 20160619
1 online resource (ix, 273 pages) : illustrations (some color).
  • Development of a Manufacturing Process for the Formation of a Nucleoside Drug Candidate
  • Development of Efficient Routes to Access C-Glycosides as SGLT-2 Inhibitors for the Treatment of Type 2 Diabetes
  • Synthetic Routes to Sofosbuvir
  • Synthetic Challenges in the Assembly of Macrocyclic HCV NS3/NS4A Protease Inhibitors: The Case of BILN 2061 and Its Analogs
  • Recent Progress in the Synthesis of Super-Statins
  • Development of Synthetic Routes to Dolutegravir
  • Story of Eribulin Mesylate: Development of the Longest Drug Synthesis.
The series Topics in Heterocyclic Chemistry presents critical reviews on present and future trends in the research of heterocyclic compounds. Overall the scope is to cover topics dealing with all areas within heterocyclic chemistry, both experimental and theoretical, of interest to the general heterocyclic chemistry community. The series consists of topic related volumes edited by renowned editors with contributions of experts in the field. All chapters from Topics in Heterocyclic Chemistry are published Online First with an individual DOI. In references, Topics in Heterocyclic Chemistry is abbreviated as Top Heterocycl Chem and cited as a journal.
1 online resource.
  • Cover; Title Page; Copyright Page; Contents; List of Contributors; About the Editor; Preface; Chapter 1
  • Origin of Chinmedomics; 1.1
  • Introduction; 1.2
  • Application and Challenges of TCM; 1.3
  • Metabolomics: An Overview; 1.4
  • Process of the Serum Pharmacochemistry of TCM; 1.5
  • Establishment and Evolution of Chinmedomics; 1.6
  • Potential Value of Chinmedomics; 1.7
  • Future Perspectives; References; Chapter 2
  • Methods and Protocols of Chinmedomics; 2.1
  • Introduction; 2.2
  • Analytical Technologies; 2.3
  • Sampling; 2.4
  • Data Extraction and Analysis
  • 2.5
  • Marker Identification and Validation2.6
  • Correlation Analysis between Marker Metabolites and Absorbed Chemical Components; 2.7
  • Goals for Chinmedomics; 2.7.1
  • Biological Mechanisms of the TCM Syndrome; 2.7.2
  • Pharmacological Effects of Formulae; 2.7.3
  • Correlation Analysis of Formulae and Syndrome for Effective Substances; 2.8
  • Chinmedomics for Yinchenhao Tang: A Case Study; 2.9
  • Conclusions; References; Chapter 3
  • Chinmedomics Advancing Drug Discovery and Development from Yinchenhao Tang; 3.1
  • Introduction; 3.2
  • Experimental Detail; 3.2.1
  • Chemicals and Materials
  • 3.2.2
  • Metabolomics Study3.2.2.1
  • Animals Handling;
  • Metabolomics Analysis Platform; 3.2.3
  • Constituents Analysis Using Serum Pharmacochemistry;
  • Animals;
  • Preparation of YCHT Samples for LC/MS Analysis In Vitro and In Vivo;
  • Instrumentation and Conditions;
  • Q-TOF/MS analysis;
  • Data Processing; 3.2.4
  • Correlation Analysis between Marker Metabolites and Absorbed Constituents; 3.2.5
  • Cell Test to Verify the Efficacy of Chemical Components Correlated with Therapeutic Effect;
  • Chemicals and Reagents
  • Isolation of Hepatocytes3.2.5.3
  • Cell Culture and Treatment;
  • Flow Cytometric Analysis;
  • Statistical Analyses; 3.3
  • Results and Discussions; 3.3.1
  • Metabolomics Analysis of Protective Function of YCHT; 3.3.2
  • LC/MS Analysis for YCHT Samples In Vitro and In Vivo;
  • Optimization of MS Conditions;
  • UPLC-UV-Q-TOF Analysis of YCHT;
  • UPLC-UV-Q-TOF Analysis of Plasma Sample after Oral YCHT Administration; 3.3.3
  • Correlation Analysis between Marker Metabolites and Absorbed Chemical Components
  • 3.3.4
  • Cell Test to Verify the Therapeutic Efficacy of the Correlated Chemical Components3.4
  • Conclusions; Chapter 4
  • Chinmedomics Approach Dissects Therapeutic Properties of ShenQiWan Acting on ShenYangXu Syndrome; 4.1
  • Introduction; 4.2
  • Experimental Detail; 4.2.1
  • Chemicals and Materials; 4.2.2
  • Metabolomics Study;
  • Animal Handling;
  • Sample Collection and Preparation;
  • UPLC-Q-TOF-HDMS Analysis;
  • Metabolic Profiling and Metabolite Analysis; 4.2.3
  • Constituents Analysis In Vitro and In Vivo;
  • Animals
  • Preparation of SQW Samples for Analysis
Chinmedomics: The Integration of Serum Pharmacochemistry and Metabolomics to Elucidate the Scientific Value of Traditional Chinese Medicine uses new experimental techniques and research to open doors in drug discovery and development related to traditional Chinese medicine (TCM). This book features a unique approach that combines chemometric analysis with metabolomics studies to illuminate significant changes that have occurred in syndrome states while simultaneously analyzing the efficacy of chemical ingredients in herbal medicines. Chapters provide cutting-edge information on traditional medicine, analytical technology, natural products, metabolomics, bioinformatics and their applications. This book provides a valuable resource for pharmacologists, pharmaceutical scientists, medicinal plant researchers, pharmacognosists and chemists working with TCM and highlights ways to further research and advances in this area in the future. * Presents a practical guide for new practitioners of Chinmedomics with insights on the current use and future development of this method* Each chapter includes an introduction, method, references to the latest literature, possible mechanisms of action and applications* Edited by the leading experts of research related to Chinmedomics.
(source: Nielsen Book Data)9780128031179 20160618
online resource (xxii, 385 pages) : illustrations (some color)
  • Ch. 1. Origin of Chinmedomics
  • Ch. 2. Methods and protocols of Chinmedomics
  • Ch. 3. Chinmedomics advancing drug discovery and development from Yinchenhao Tang
  • Ch. 4. Chinmedomics approach dissects therapeutic properties of ShenQiWan acting on ShenYangXu Syndrome
  • Ch. 5. Metabolic profiling and biomarkers analysis of jaundice syndrome
  • Ch. 6. Metabolic profiling and biomarkers analysis of GanYu PiXu Syndrome
  • Ch. 7. Metabolic profiling and biomarkers of Yinhuang Syndrome and evaluation of Yinchensini Tang
  • Ch. 8. Metabolite profiling and biomarkers analysis of jaundice sydrome-related animal models
  • Ch. 9. Metabolomic evaluation of hepatoprotective effect of Yinchenhao Tang and its major bioactive constituents
  • Ch. 10. Metabolomics and proteomics annotate therapeutic mechanisms of geniposide
  • Ch. 11. Metabolic profiling and potential biomarkers of ShenYinXu Syndrome and the therapeutic effect of Liuweidihuang Wan
  • Ch. 12. Metabolic profiling of healthy persons treated with Liuweidihuang Wan
  • Ch. 13. Metabolic profiling and potential biomarkers analysis of ShenYangXu Syndrome
  • Ch. 14. Metabolic evaluation of ShenQiWan nourishing ShenYangXu Syndrome
  • Ch. 15. Metabolic profiling and biomarkers analysis of XinQiXu Syndrome
  • Ch. 16. Active constituents screening based on correlation analysis between marker metabolites and the absorbed constituents in WenXin formulae
  • Ch. 17. Targeted synergism effects of the combined active constituents of Yinchenhao Tang
  • Ch. 18. Metabolic profiling and biomarkers of Type 2 Diabetes and the effective evaluation of the Tinaqi Jiangtang capsule
  • Ch. 19. Metabolic biomarkers of alcohol liver damage and the intervention effect of Yinchenhao Tang
  • Ch. 20. Metabolic profiling and biomarkers analysis of insomnia and the intervention effects of Suanzaoren Decoction and its related active ingredients
  • Ch. 21. Metabolic biomarkers of nonbacterial prostatisis and the treatment evaluation of Phellodendri Amurensis cortex and its main components
  • Ch. 22. Metabolic profiling provides a system for the understanding of Alzheimer's Disease in rates post-treatment with Kaixin San
  • Ch. 23. Metabolic profiles delineate the effect of Shengmai San on Alzheimer's Disease in rats
  • Subject Index.
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