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• Prologue: A new door
• A renaissance
• Natural history: bemushroomed
• History: the first wave. Part I: the promise ; Part II: the crack-up
• Travelogue: journeying underground. Trip one: LSD ; Trip two: Psilocybin ; Trip three: 5-MeO-DMT (or, the toad)
• The neuroscience: your brain on psychedelics
• The trip treatment: Psychedelics in psychotherapy. One: Dying ; Two: Addiction ; Three: Depression ; Coda: Going to meet my default mode network
• Epilogue: In praise of neural diversity.

"When Michael Pollan set out to research how LSD and psilocybin (the active ingredient in magic mushrooms) are being used to provide relief to people suffering from difficult-to-treat conditions such as depression, addiction and anxiety, he did not intend to write what is undoubtedly his most personal book. But upon discovering how these remarkable substances are improving the lives not only of the mentally ill but also of healthy people coming to grips with the challenges of everyday life, he decided to explore the landscape of the mind in the first person as well as the third. Thus began a singular adventure into the experience of various altered states of consciousness, along with a dive deep into both the latest brain science and the thriving underground community of psychedelic therapists ..."-- Provided by publisher.

• Feature Boxes xv Preface to the Second Edition xvii Preface to the First Edition xix Acknowledgments xxi About the Companion Website xxiii
• 1 Inorganic Chemistry Basics 1 1.1 Introduction 1 1.2 Crystal Field Theory 1 1.3 Molecular Orbital Theory 12 1.4 Absorption Spectra of Metal Complexes 22 1.5 Magnetic Properties of Metal Complexes 33 1.6 Structure and Reactivity of Metal Complexes 35
• 2 Metallo-Drugs and Their Action 59 2.1 Introduction 59 2.2 Proteins asTargets forMetallo-Drugs 59 2.3 DNAas aTarget forMetallo-Drugs 71 2.4 Reaction of Metal Complexes in the Biological Milieu 76 2.5 Evaluating the Pharmacological Effects of Agents 79 2.6 FromDiscoverytotheClinic 82
• 3 Platinum Drugs for Treating Cancer 91 3.1 Introduction 91 3.2 Cisplatin 91 3.3 Carboplatin 115 3.4 Oxaliplatin 126 3.5 RegionallyUsedPlatinumDrugs 133 3.6 Platinum Agents in Preclinical Development 135
• 4 Anticancer Agents Beyond Cisplatin 157 4.1 Introduction 157 4.2 Ruthenium Anticancer Agents 157 4.3 Gold Anticancer Agents 173 4.4 Titanium Compounds for Treating Cancer 181 4.5 Gallium for Treating Cancer 187 4.6 Other Anticancer Active Metal Complexes 194
• 5 Responsive Metal Complexes 217 5.1 Introduction 217 5.2 Prodrug Activation by Redox 217 5.3 ProdrugActivationbypH 225 5.4 Prodrug Activation by Enzymes 227 5.5 ProdrugActivationbyLight 229 5.6 Photodynamic Therapy 233
• 6 Metal Complexes for Treating Arthritis and Diabetes 245 6.1 Introduction 245 6.2 ChemistryofGoldinBiologicalMedia 245 6.3 Gold Compounds for Treating Arthritis 247 6.4 Vanadium Compounds for Treating Diabetes 263
• 7 Metal Complexes for Killing Parasites, Bacteria and Viruses 285 7.1 Introduction 285 7.2 Malaria 285 7.3 Leishmaniasis 293 7.4 American Trypanosomiasis (Chagas Disease) 298 7.5 Human African Trypanosomiasis 301 7.6 Tuberculosis 301 7.7 PepticUlcerDisease 306 7.8 Syphilis 311 7.9 Bacterial Infections 312 7.10 Acquired Immunodeficiency Syndrome (AIDS) 314
• 8 Metal Ion Imbalance in the Body 329 8.1 Introduction 329 8.2 Alzheimer s Disease 329 8.3 LithiumandtheBrain 337 8.4 Wilson s Disease: Copper Overload 338 8.5 Menkes Disease: Copper Deficiency 340 8.6 Beta-Thalassemia: IronOverload 342 8.7 Iron-Deficiency Anemia 344 8.8 Calcium Imbalance 344 8.9 ChelationTherapy 346
• 9 Metal Complexes for Detecting Disease 357 9.1 Introduction 357 9.2 Technetium in Diagnostic Nuclear Medicine 358 9.3 Metal Compounds as Contrast Agents for MRI 371 9.4 Radiotherapy 382
• 10 Nanomedicine 395 10.1 Introduction 395 10.2 Circulation, Uptake, and Elimination of Nanoparticles 396 10.3 Nanoscience for Treating Cancer 407 10.4 Nanoparticles for Detecting Disease 419 10.5 Theranostic Nanoparticles 426 10.6 Cytotoxicity of Nanoparticles 428 Index 441.
• (source: Nielsen Book Data)

Working from basic chemical principles, Metals in Medicine 2nd Edition describes a wide range of metal-based agents for treating and diagnosing disease. Thoroughly revised and restructured to reflect significant research activity and advances, this new edition contains extensive updates and new pedagogical features while retaining the popular feature boxes and end-of-chapter problems of the first edition. Topics include: Metallo-Drugs and their actionPlatinum drugs for treating cancer Anticancer agents beyond cisplatin including ruthenium, gold, titanium and galliumResponsive Metal ComplexesTreating arthritis and diabetes with metal complexesMetal complexes for killing bacteria, parasites and virusesMetal ion imbalance and its links to diseases including Alzheimer s, Wilson s and Menkes disease Metal complexes for detecting diseaseNanotechnology in medicine Now in full colour, Metals in Medicine 2nd Edition employs real-life applications and chapter-end summaries alongside feature boxes and problems. It provides a complete and methodical examination of the use of metal complexes in medicine for advanced undergraduate and postgraduate students in medicinal inorganic chemistry, bioinorganic chemistry, biochemistry, pharmacology, biophysics, biology and bioengineering. It is also an invaluable resource for academic researchers and industrial scientists in inorganic chemistry, medicinal chemistry and drug development.
(source: Nielsen Book Data)

• Introduction Overview: General Principles Combination of Cancer Drugs Plant-Derived Active Phytochemicals Show Various Biologic and Pharmacological Activities in Cancer Therapeutic Benefits of Phytochemicals Mechanism of Cancer Drug Action Inhibition of Cancer Growth by Herbal Medicines Herbal Formulations in Folk Medicine Exploration of Herbal Medicine List of Selected Phytochemicals.
• (source: Nielsen Book Data)

Chinese herbal medicine represents complementary or adjunctive therapies that often can improve the efficacy of Western medicine to achieve the pharmacological effects, especially in cancer treatment. However, the combination of herbs with therapeutic drugs can raise potential health risk. Building a bridge between Western medicine and herbal medicines, Active Phytochemicals from Chinese Herbal Medicines: Anti-Cancer Activities and Mechanisms gives you useful information on how integrated medicines can work for cancer therapy. It discusses the therapeutic uses of phytochemicals, adverse effects, and interactions with (Western) cancer drugs. The author takes a unique approach to integrated pharmacology of herbal medicines, examining the development of phytochemicals and their mechanisms of action in the context of the cancers and diseases they are used to treat. He covers biologic action of the active phytochemicals at the molecular, cellular, and organ levels. The book covers the principles of the interaction of phytochemicals and the related drug actions. It also addresses the common pathways affecting cancer development before discussing the phytochemical classes and specific phytochemicals that have been recently reported in journal papers for the management of cancer and other diseases. Highlighting the increasingly important aspects of pharmacology, including health benefit and drawbacks of phytochemcials, the book presents the relevant background of the biochemistry of the cancer. It includes illustrations and tables with adverse reactions that highlight important issues related to phytochemical actions. These features and more make the book a useful reference on phytochemicals obtained from herbal medicines. It blends coverage of fundamental mechanisms of anti-cancer action and the use of phytochemicals to manage cancers and other human diseases, allowing you to explore how herbal medicines can enhance conventional protocols.
(source: Nielsen Book Data)

• Preface Editor Contributors Nanomaterials for Drug Delivery Stimuli-Responsive Nanostructured Silica Matrix Targeting Drug Delivery Applications Sanghoon Kim, Nadia Canilho, and Andreea Pasc Gold Nanoparticles: A Novel and Promising Avenue for Drug Delivery Shuaidong Huo, Xin Cao, Zhongbo Hu, and Xing-lie Liang Liposomes as a Drug Delivery System Kacoli Banerjee, Shubhadeep Banerjee, and Mahitosh Mandai Nanocarriers for Breast Cancer Therapeutics Deepti Rana, Shylaja Arulkumar, Akshayaa Ganesh, and Murugan Ramalingam Nanoparticles as a Promise for Host Defense Peptide Therapeutics Carlos Lopez-Abarrategui, Anselmo J. Otero-Gonzalez, Annia Alba-Menendez, Edilso Reguera, and Octavio Luiz Franco Novel Nanostructured Bioactive Restorative Materials for Dental Applications Mary Anne S. Melo, Lei Cheng, Ke Zhang, Michael D. Weir, Xuedong Zhou, Yuxing Bai, Lidiany K.A. Rodrigues, and Hockin H.K. Xu Redox-Triggered, Biocompatible, Inorganic Nanoplatforms for Cancer Theranostics Xin-Chun Huang, Yun-Ling Luo, and Hsin-Yun Hsu Antimicrobial Nanomaterials Surface Characteristics Dictate Microbial Adhesion Ability Klemen Bohinc, Mojca Jevsnik, Rok Fink, Goran Drazic, and Peter Raspor Antimicrobial Polymers Based on Nanostructures: A New Generation of Materials with Medical Applications Maria Isabel Gonzalez-Sanchez, Stefano Perni, and Polina Prokopovich Nanomaterials in Biosensors Recent Advances in Nanodiagnostic Techniques for Infectious Agents Muhammad Ali Syed Chromogenic Biosensors for Pathogen Detection Alok P. Das, B. Bal, and P.S. Mahapatra Electrochemical Biosensors for Detecting DNA Damage and Genotoxicity Ali A. Ensafi and Esmaeil Heydari-Bafrooei In Vivo Molecular Imaging with Quantum Dots: Toward Multimodality and Theranostics Sarah P. Yang, Shreya Goel, and Weibo Cai Surface Modifications by Polymers for Biosensing Applications Laura Sola, Chiara Finetti, Paola Gagni, Marcella Chiari, and Marina Cretich Safety of Nanomaterials Nanotoxicity: A Mechanistic Approach Indarchand Gupta, Swapnil Gaikwad, Avinash Ingle, Kateryna Kon, Nelson Duran, and Mahendra Rai Index.
• (source: Nielsen Book Data)

Biological and Pharmaceutical Applications of Nanomaterials presents the findings of cutting-edge research activities in the field of nanomaterials, with a particular emphasis on biological and pharmaceutical applications. Divided into four sections-nanomaterials for drug delivery, antimicrobial nanomaterials, nanomaterials in biosensors, and safety of nanomaterials-this book: * Covers topics such as stimuli-responsive nanostructured silica matrixes, gold nanoparticles, and liposomes for targeting drug delivery and dental applications * Describes the use of nanocarriers and nanoparticles as cancer and peptide therapeutics, the influence of surface characteristics on microbial adhesion, and the latest developments in antimicrobial nanostructured polymers for medical applications * Discusses recent advances in nanodiagnostic techniques for infectious agents, chromogenic biosensors for pathogen detection, electrochemical biosensors for detecting DNA damage and genotoxicity, and molecular imaging with quantum dots including surface modifications by polymers for biosensing applications Featuring contributions from field experts and researchers in industry and academia, Biological and Pharmaceutical Applications of Nanomaterials provides state-of-the-art information on nanomaterials and their use in drug delivery, infection control, and biomedicine.
(source: Nielsen Book Data)

• Preface IX
• General Remarks XI
• 1 Medicinal Gases Manufacturing 1
• 1.1 Where Do the Gases Come from? 1
• 1.1.1 Gases Obtained from Air: Oxygen, Nitrogen, Argon, Xenon 1
• 1.1.1.1 Oxygen 6
• 1.1.1.2 Nitrogen 8
• 1.1.1.3 Argon 9
• 1.1.1.4 Xenon 9
• 1.1.2 Gases Separated from Other Sources: Helium, Carbon Monoxide, Methane 11
• 1.1.2.1 Helium 11
• 1.1.2.2 Carbon Monoxide 15
• 1.1.2.3 Methane 17
• 1.1.3 Gases from Chemical Synthesis: Carbon Dioxide, Nitric Oxide, Nitrous Oxide 17
• 1.1.3.1 Carbon Dioxide 17
• 1.1.3.2 Nitric Oxide 18
• 1.1.3.3 Nitrous Oxide 19
• 1.1.4 Gas Mixtures for Inhalation 20
• 1.1.4.1 Reconstituted (Synthetic) Air 21
• 1.1.4.2 Compressed Medical Air 22
• 1.1.4.3 Nitrous Oxide 50 vol% in Oxygen 22
• 1.1.4.4 Nitric Oxide Approximately 1000 ppm in Nitrogen 22
• 1.1.4.5 Mixtures with the General Composition Carbon Monoxide, Helium in Synthetic Air (Carbon Monoxide Ranging between 0.2 and 0.3 vol%, Helium between 8 and 18 vol%) 22
• 1.1.4.6 Carbogen (5 vol% Carbon Dioxide in Oxygen) 22
• 1.1.5 Gas Mixtures for Reference Calibration Gas Mixtures 23
• 2 Pressure Vessels and Their Accessories 27
• 2.1 Transportable Pressure Receptacles: Pressure Cylinders 29
• 2.1.1 Seamless Steel Cylinders 30
• 2.1.2 Seamless Aluminum Cylinders 31
• 2.1.2.1 Specifics of Aluminum Cylinders 33
• 2.1.3 Welded Steel Vessels 34
• 2.1.4 LightweightWrapped Steel or Aluminum Cylinders 34
• 2.1.5 Pharmaceutical View on Cylinders as Containment for Drugs 36
• 2.1.5.1 European Pharmacopoeia View on Cylinders as Containment for Drugs 37
• 2.1.5.2 Inner and Outer Surfaces of Cylinders 37
• 2.1.6 Accessories for Cylinders: Valves 39
• 2.1.6.1 Accessories for Valves: Gaskets 42
• 2.1.6.2 Valves with Integrated Residual Pressure/Nonreturn Cartridge (NRV/PRV) 43
• 2.1.6.3 Integrated Valves 44
• 2.2 Non-transportable Pressure Receptacles: Stationary (Pressure) Tanks for Cryogenic Liquids 46
• 2.2.1 Safety Measures on Stationary Tanks 47
• 2.2.2 European Pharmacopoeia View on Cryo-Tanks as Containment for Drugs 48
• 2.2.3 Inner and Outer Surfaces of Cryo-Tanks 49
• 2.2.4 Accessories for Cryo-Containers 50
• 2.2.5 Choice of the Good Location for Tanks 52
• 2.3 Medicinal Gas Pipeline Systems (MGPS) 53
• 2.3.1 Elements of a Medical Gas Pipeline System (MGPS) 56
• 2.3.1.1 Gas Terminal Units (Wall Sockets) 57
• 2.3.2 Tests and Checks before Going Onstream 60
• 2.3.3 Operation of a Central Medical Supply System 60
• 2.3.4 Maintenance and Service, Pharmaceutical View 62
• 3 AnalyticalMethods for Gases (as Described in Ph. Eur.) 65
• 3.1 Sampling 65
• 3.1.1 Permanent Gases 65
• 3.1.2 Gases Liquefied under Pressure 66
• 3.1.3 Cryogenic Gases 69
• 3.2 Gas Analytical Methods 71
• 3.2.1 Infrared (IR-) Spectrometry 73
• 3.2.1.1 Calibration 74
• 3.2.2 Gas Chromatography (Lit) 76
• 3.2.2.1 Calibration 80
• 3.2.3 Chemiluminescence 80
• 3.2.3.1 Calibration 81
• 3.2.4 Paramagnetic Measurement 82
• 3.2.4.1 Calibration 82
• 3.2.5 Moisture Measurement 83
• 3.2.5.1 Calibration 85
• 3.2.6 Fluorescence Analysis 85
• 3.2.6.1 Calibration 86
• 3.2.7 Test Tubes 86
• 4 Monographs for Gases in the European and National Pharmacopoeias 91
• 4.1 European Pharmacopoeia Specifications 91
• 4.1.1 General Composition of Monographs 91
• 4.1.2 Use of Monographs in the Industry 93
• 4.1.3 Other Descriptions from the Ph. Eur. 96
• 5 Production of Medical Gases Special Handling to Comply with GMP Rulings 99
• 5.1 History Gases Becoming Medicinal Products 99
• 5.2 Classification of Gases or Gas Mixtures as Medicinal Products 102
• 5.2.1 Conclusion 105
• 5.3 Basic Requirements (Volume 4, Part I) ([79] GMP-Guidelines) 107
• 5.3.1 Pharmaceutical Quality System (PQS) and ICH Q10 107
• 5.3.2 Personnel 109
• 5.3.3 Premises and Equipment 110
• 5.3.3.1 Annex 6 112
• 5.3.4 Documentation 112
• 5.3.5 Production 117
• 5.3.5.1 Annex 6 118
• 5.3.6 Quality Control 119
• 5.3.6.1 Annex 6 121
• 5.3.7 Outsourced Activities 121
• 5.3.8 Complaints and Product Recall 122
• 5.3.9 Self-Inspection 124
• 5.4 Basic Requirements for Active Substances Used as Starting Materials (Part II of the GMP-Guide) 124
• 5.4.1 Annex 6 126
• 5.5 GMP-Related Documents (Part III of the GMP Guide) 126
• 5.5.1 Site Master File (SMF) 126
• 5.5.2 ICH-Q9 Quality Risk Management 128
• 5.5.3 Q10 Note for Guidance: PQS 128
• 5.5.4 MRA Batch Certificate 128
• 5.5.5 Written Confirmation 129
• 6 Requirements of the New Good Distribution Practice (GDP) 131
• 6.1 Gas in Packages No Difference from Other Medicinal Products 131
• 6.1.1 GDP Targets and Tools 131
• 6.1.1.1 GDP Quality Management 132
• 6.1.1.2 GDP Personnel 133
• 6.1.1.3 GDP Premises and Equipment 133
• 6.1.1.4 GDP Documentation 133
• 6.1.1.5 GDP Operations 135
• 6.1.1.6 GDP Complaints, Returns, Suspected Falsified Medicinal Products, and Medicinal Product Recalls 135
• 6.1.1.7 GDP Outsourced Activities 136
• 6.1.1.8 GDP Self-Inspections 136
• 6.1.1.9 GDP Transportation 136
• 6.1.1.10 GDP Specific Provisions for Brokers 136
• 6.1.1.11 GDP Conclusions 136
• 7 Safe Handling of Gases 139
• 7.1 Safe Handling of Gases 139
• 7.1.1 Hazards and Risks 139
• 7.1.2 Safety and the Pressure Container 142
• 7.1.3 Main Technical Risks 142
• 7.1.3.1 Storage 142
• 7.1.3.2 Transport 143
• 7.1.3.3 Application 144
• 7.1.4 Pharmaceutical Safety 144
• 7.2 Safety and Pressure 147
• 7.3 The Compound s Chemical Properties 148
• 7.4 Cryogenic Liquids: Low Temperature and Vast Development of Gas 151
• 7.5 Gases Tapped from Piping Systems: Cross-Contamination and Contamination by Insufficient Handling, Memory Effects 154
• References 157
• Abbreviations 163
• Index 165.
• (source: Nielsen Book Data)

Covering the entire spectrum of medical gases, this ready reference offers a comprehensive overview of production, medical gas equipment, medical gas verification, and medical gas safety standards. With a clear focus throughout on safety, the text recommends environmentally responsible manufacturing practices during each step of the process: manufacture, storage, transport, distribution, and in applications. It also discusses standards and regulations, in particular those of the European Union. An essential guide for researchers and professionals whose work includes the manufacture, handling, or use of medical gases.
(source: Nielsen Book Data)

• PART 1 CONSTITUENTS, HISTORY, INTERNATIONAL CONTROL, CULTIVATION AND PHENOTYPES OF CANNABIS
• PART 2 PHARMACOLOGY, PHARMACOKINETICS, METABOLISM AND FORENSICS
• PART 3 MEDICINAL CANNABIS AND CANNABINOIDS: CLINICAL DATA
• PART 4 APPROVED THERAPEUTIC TARGETS FOR PHYTOCANNABINOIDS: PRECLINICAL PHARMACOLOGY
• PART 5 SOME POTENTIAL THERAPUTIC TARGETS FOR PHYTOCANNABINOIDS
• PART 6 RECREATIONAL CANNABIS: SOUGHT-AFTER EFFECTS, ADVERSE EFFECTS, DESIGNER DRUGS AND HARM MINIMIZATION.
• (source: Nielsen Book Data)

Truly global in scope and with contributions from leading researchers around the world, The Handbook of Cannabis is the definitive resource on this fascinating drug. Combining scientific perspectives and clinical applications, it covers a vast array of topics, from why over the centuries cannabis has been used as a medicine, through the regulations facing those wishing to self-administer cannabis or provide cannabis-based medicines, to the chemical structure of its many constituents and the rapidly growing group of synthetic cannabinoids that are currently being used for 'legal highs'. With each chapter written by a group of one or more internationally recognised subject experts, it provides academics and researchers with authoritative scientific material on the main pharmacological actions and their effects, as well as their pharmacokinetics, metabolism, and forensic detection. In addition it also examines the complex morphology, cultivation, harvesting, and processing of cannabis and the ways in which the plant's chemical composition can be controlled. As well as offering a raft of scientific information there is extensive coverage of cannabinoid-based medicines. Helping readers to identify and evaluate their benefits, chapters explore pharmacological actions and the effects that seem to underlie approved therapeutic uses, how they are currently used to treat certain disorders, and the ever-growing number of wide-ranging potential clinical applications. There is also coverage of both the legal and illegal sources of cannabis, including 'coffee shops' and 'cannabis dispensaries'. The complex issue of 'recreational cannabis' is also tackled. The sought-after and adverse psychological and non-psychological effects are described and discussions are included on how some adverse effects can be lessened by at least one constituent of cannabis, and that it might be possible to reduce the harm that cannabis does to some by changing current regulatory policies. The Handbook of Cannabis is a one-stop reference; essential reading for all clinicians, pharmacologists, psychologists, and psychiatrists interested in this drug, as well as those working in the field of public health.
(source: Nielsen Book Data)

This well-established international series examines major areas of basic and clinical research within neuroscience, as well as emerging and promising subfields. This volume concentrates on Neuroimmune Signaling in Drug Actions and Addictions. This book looks at neuroimmune signaling in drug actions and addictions in the light of the newest scholarly discoveries and insights.
(source: Nielsen Book Data)

• Chapter 1: Getting Started 1.1
• Advancing New Treatments to the Clinic within Academia
• Daria Mochly-Rosen 1.2
• Overview of Drug Discovery and Development
• Kevin Grimes 1.3
• Assessing Clinical Need
• Kevin Grimes 1.4
• Target Product Profile (TPP)
• Robert Lum 1.5
• Project Management and Project Planning
• Rebecca Begeley and Daria Mochly-Rosen
• Chapter 2: Discovery and Preclinical Work 2.1
• Robustness of Preclinical Studies Daria Mochly-Rosen 2.2
• Repurposing Drugs
• Kevin Grimes 2.3
• Developing Assays for High Throughput Screening (HTS)
• Bruce Koch 2.4
• Medicinal Chemistry and Lead Optimization
• Daniel A. Erlanson 2.5
• Vaccine Development
• Harry Greenberg 2.6
• When to Begin Animal Studies
• Daria Mochly-Rosen 2.7
• In vivo pharmacology: Multiple Roles in Drug Discovery
• Simeon Taylor 2.8
• Pharmacokinetics and ADME Properties
• Werner Rubas and Emily Egeler 2.9
• Route of Administration and Drug Formulation Terrence F. Blaschke 2.10
• Preclinical Safety Studies
• Michael Taylor and Kevin Grimes
• Chapter 3: Preparing for the Clinic 3.1
• Regulatory Considerations in Product Development
• Carol Karp 3.2
• Manufacturing and Quality Control
• Susan Wade 3.3
• Technical Development and Manufacturing of Biological Products
• Mark Backer 3.4
• Clinical Trial Design
• Ted McCluskey 3.5
• Overview of Clinical Trials
• Ted McCluskey
• Chapter 4: Transferring Technology 4.1
• Intellectual Property
• Judy Mohr 4.2
• Working with the University Technology Transfer Office
• Katharine Ku 4.3
• Avoiding Conflicts of Interest
• Emily Egeler 4.4
• Working with the University Compliance Office
• Jennifer Swanton Brown, Nicholas Gaich, and Steven Alexander
• Chapter 5: Commercialization and Entrepreneurship 5.1
• Selecting the Market for Your Drug
• Lilliane Brunner Halbach 5.2
• Commercial Assessments
• Julie Papanek 5.3
• Making a Compelling Pitch to Potential Investors
• Leon Chen 5.4
• Venture Capital Funding
• Kevin Kinsella 5.5
• Not-For-Profit Drug Development
• Eugenio L. de Hostos 5.6
• Legal Aspects of a Start-up Biotechnology Company
• Alan C. Mendelson, Peter E. Boyd, and Christopher M. Reilly 5.7
• Founder Preferred Stock
• Scott M. Iyama and Stephen J. Venuto 5.8
• Plan, Organize, Motivate and Control
• John Walker
• Chapter 6: Concluding Thoughts 6.1
• A Call to Action: Changing How We Pursue Drug Discovery and Development
• Steven Schow.
• (source: Nielsen Book Data)

Written by the founders of the SPARK program at Stanford University, this book is a practical guide designed for professors, students and clinicians at academic research institutions who are interested in learning more about the drug development process and how to help their discoveries become the novel drugs of the future. Often many potentially transformative basic science discoveries are not pursued because they are deemed 'too early' to attract industry interest. There are simple, relatively cost-effective things that academic researchers can do to advance their findings to the point that they can be tested in the clinic or attract more industry interest. Each chapter broadly discusses an important topic in drug development, from preclinical work in assay design through clinical trial design, regulatory issues and marketing assessments. After the practical overview provided here, the reader is encouraged to consult more detailed texts on specific topics of interest.
(source: Nielsen Book Data)

• Preface vii Contributors ix About the Authors xi
• 1 Transition Metal Catalysis in the Pharmaceutical Industry 1 Carl A. Busacca, Daniel R. Fandrick, Jinhua J. Song, and Chris H. Senanayake (Boehringer Ingelheim Pharmaceuticals)
• 2 Selected Applications of Transition Metal-Catalyzed Carbon--Carbon Cross-Coupling Reactions in the Pharmaceutical Industry 25 Hong C. Shen (Roche)
• 3 Selected Applications of Pd- and Cu-Catalyzed Carbon--Heteroatom Cross-Coupling Reactions in the Pharmaceutical Industry 97 Jingjun Yin (Merck)
• 4 Asymmetric Cross-Coupling Reactions 165 Vince Yeh (Novartis) and William A. Szabo (Consultant in Drug Development)
• 5 Metathesis Reactions 215 Oliver R. Thiel (Amgen)
• 6 Transition Metal-Catalyzed Synthesis of Five- and Six-Membered Heterocycles 257 Cheol K. Chung (Merck) and Matthew L. Crawley (Main Line Health)
• 7 Oxidative Catalysis 277 Lamont Terrell (GlaxoSmithKline)
• 8 Industrial Asymmetric Hydrogenation 315 Hans-Ulrich Blaser (Solvias) Index 343.
• (source: Nielsen Book Data)

This book focuses on the drug discovery and development applications of transition metal catalyzed processes, which can efficiently create preclinical and clinical drug candidates as well as marketed drugs. The authors pay particular attention to the challenges of transitioning academically-developed reactions into scalable industrial processes. Additionally, the book lays the groundwork for how continued development of transition metal catalyzed processes can deliver new drug candidates. This work provides a unique perspective on the applications of transition metal catalysis in drug discovery and development -- it is a guide, a historical prospective, a practical compendium, and a source of future direction for the field.
(source: Nielsen Book Data)

• Matrix Metalloproteinases.- Specificity of Binding with Matrix Metalloproteinases.- The Gelatinases and Their Inhibitors: The Structure-Activity Relationships.- Advances in Studies on Collagenase Inhibitors.- Hydroxamic Acids as Matrix Metalloproteinase Inhibitors.- Quantitative Structure-Activity Relationship Studies on Sulfonamide-Based MMP Inhibitors.- Matrix Metalloproteinase Inhibitors as Investigative Tools in the Pathogenesis and Management of Vascular Disease.
• (source: Nielsen Book Data)

Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in many physiological and pathological processes. The field of MMP research is very important due to the implications of the distinct paralogs in both human physiology and pathology. Over-activation of these enzymes results in tissue degradation, producing a wide array of disease processes such as rheumatoid arthritis, osteoarthritis, tumor growth and metastasis, multiple sclerosis, congestive heart failure, and others. Thus MMP inhibitors are candidates for therapeutic agents to combat a number of diseases. The present book discusses the design and development of different classes of inhibitors of important classes of MMPs, such as gelatinases and collagenases. The articles focus specifically on structure-activity relationships of all classes of compounds and on their modes of action and specificity of binding with the receptors based on experimental and theoretical studies. These studies constitute a valuable asset for all those involved in drug development.
(source: Nielsen Book Data)

• Introduction Part I. Physicochemical Aspects of Drug Dissolution and Solubility Aqueous Solubility in Discovery Chemistry, DMPK and Biological Assays Gastrointestinal Dissolution and Absorption of Class II Drugs In Silico Prediction of Aqueous Solubility Part II. Physicochemical and Biological Studies of Membrane Permeability and Oral Absorption Physico-chemical Approaches to Drug Absorption High-throughput Measurement of Physicochemical Properties (pKa, solubility, log D, permeability) Cell Cultures for Permeability Assessment in Drug Discovery Use of Animals for the Determination of Absorption and Bioavailability In vivo Permeability Studies in the GI Tract of Humans Part III Role of Transporters and Metabolism in Oral Absorption Transporters in the GI Tract Hepatic Drug Transport The Importance of Gut Wall Metabolism in Determining Drug Bioavailability Modified Cell Lines to Assess Active Transport and Metabolism during Absorption Part IV Computational Approaches to Drug Absorption and Bioavailability Calculated Molecular Properties and Multivariate Statistical Analysis Computational Absorption Prediction In Silico Prediction of Bioavailability Simulation of Absorption, Metabolism, and Bioavailability P-Glycoprotein Structure-Activity Relationships Part V Drug Development Issues Application of the Biopharmaceutical Classification System Now and in the Future Prodrugs Modern Delivery Strategies: Physiological Considerations for Orally Administered Medications The Promise of Nanotechnology in Drug Delivery.
• (source: Nielsen Book Data)

This work offers the gold standard for industrial research now completely revised in line with current trends in the field, with all contributions extensively updated or rewritten. In 21 chapters readers can benefit from the key working knowledge of today's leading pharmaceutical companies, including Pfizer, AstraZeneca, and Roche. Drug developers from industry and academia present all the factors governing drug bioavailability, complete with practical examples and real-life data. Part I focuses on in vitro and in vivo measurements of physicochemical properties, such as membrane permeability and ionization. Part II discusses solubility and gastrointestinal absorption, while the third part is devoted to metabolism and excretory mechanisms.The much revised and expanded part IV surveys current in silico approaches to predict drug properties needed to estimate the bioavailability of any new drug candidate. The final part shows how poor bioavailability may be improved by various approaches during the development process. No other publication offers the same level of treatment on this crucial topic in modern drug development.
(source: Nielsen Book Data)

• Chapter 1: FROM ERGOTISM TO LSD--
• Chapter 2: FROM OPIUM TO HEROIN--
• Chapter 3: COCA AND COCAINE--
• Chapter 4: CANNABIS: HASHISH, MARIJUANA, CHAEAS AND BHANG--
• Chapter 5: BELLADONNA, MANDRAKE AND DATURAS--
• Chapter 6: PEYOTE AND AMPHETAMINES--
• Chapter 7: FLY AGARIC--
• Chapter 8: ABSINTHE.
• (source: Nielsen Book Data)

Timothy Leary's advice to "tune in, turn on and drop out" was a 1960s exhortation to experiment with LSD, but humans had been consuming ergot alkaloids related to lysergic acid diethylamide for at least a thousand years. Opium has been around even longer with its medicinal uses being known to the Ancient Sumerians as long ago as 3400 BC. This is the first book to cover all of the major psychoactive drugs (both natural and synthetic) in one volume, and the only one to cover all aspects of these drugs from their anthropological and sociological influences through to their chemistry and pharmacology. It covers a range of substances including LSD, opium, heroin, cocaine, cannabis, peyote, belladonna, mandrake, and absinthe. The book is highly readable and concentrates on the characters (e.g. authors, painters, pop stars, hippies, politicians and drug barons), both famous and infamous, who have ensured that psychoactive drugs hold an enduring fascination and interest for everyone. The basic chemistry and pharmacological activity covered together with a brief account of useful drugs that have emerged from a study of the psychoactive ones.
(source: Nielsen Book Data)

• List of Contributors. Preface. A Personal Foreword. I General Aspects.
• 1 Why Drugs Fail - A Study on Side Effects in New Chemical Entities (Daniela Schuster, Christian Laggner, Thierry Langer). 1.1 Introduction. 1.2 Drugs Withdrawn from the Market between 1992 and 2006 Listed Alphabetically. 1.3 Borderline Cases. 1.4 Investigational Drugs That Failed in Clinical Phases from 1992 to
• 2002. 1.5 Strategies for Avoiding Failure. 1.6 An Unusual Case: The Revival of Thalidomide. References.
• 2 Use of Broad Biological Profiling as a Relevant Descriptor to Describe and Differentiate Compounds: Structure-In Vitro (Pharmacology-ADME)-In Vivo (Safety) Relationships (Jonathan S. Mason, Jacques Migeon, Philippe Dupuis, Annie Otto-Bruc). 2.1 Introduction. 2.3 Structure-In Vitro Relationships. 2.4 Chemogenomic Analysis - Target-Target Relationships. 2.5 In Vitro-In Vivo Relationships - Placing Drug Candidates in the Context of BioPrint1. 2.6 A Perspective for the Future. References. II Antitargets: Ion Channels and GPCRs.
• 3 Pharmacological and Regulatory Aspects of QT Prolongation (Fabrizio De Ponti). 3.1 Introduction. 3.2 hERG: Target Versus Antitarget. 3.3 Pharmacology of QT Prolongation. 3.4 Significance of Drug-Induced QT Prolongation. 3.5 Regulatory Aspects of QT Prolongation. 3.6 Conclusions. References.
• 4 hERG Channel Physiology and Drug-Binding Structure-Activity Relationships (Sarah Dalibalta, John S. Mitcheson). 4.1 Introduction. 4.2 hERG Channel Structure. 4.3 hERG Potassium Channels and the Cardiac Action Potential. 4.4 Mutations in hERG Are Associated with Cardiac Arrhythmias. 4.5 Acquired Long QT Syndrome. 4.6 Drug-Binding Site of hERG. 4.7 Structural Basis for hERG Block. 4.8 Alternative Mechanisms of Block. 4.9 Role of Inactivation in hERG Block. 4.10 Inhibition of hERG Trafficking by Pharmacological Agents. 4.11 Computational Approaches to Predict hERG Kt Channel Block. 4.12 Conclusions. References.
• 5 QSAR and Pharmacophores for Drugs Involved in hERG Blockage (Maurizio Recanatini, Andrea Cavalli). 5.1 Introduction. 5.2 Ligand-Based Models for hERG-Blocking Activity. 5.3 Ligand-Derived Models in the Light of the hERG Channel Structure. 5.4 Conclusions. References.
• 6 GPCR Antitarget Modeling: Pharmacophore Models to Avoid GPCR-Mediated Side Effects (Thomas Klabunde, Andreas Evers). 6.1 Introduction: GPCRs as Antitargets. 6.2 In Silico Tools for GPCR Antitarget Modeling. 6.3 GPCR Antitarget Pharmacophore Modeling: The a1a Adrenergic Receptor. 6.4 Summary. References.
• 7 The Emergence of Serotonin 5-HT2B Receptors as DRUG Antitargets (Vincent Setola, Bryan L. Roth). 7.1 Receptorome Screening to Identify Drug Targets and Antitargets. 7.2 Post-Receptorome Screening Data Implicate 5-HT2B Receptors in Drug-Induced VHD and PH. 7.3 Drug Structural Classes and VHD/PH. 7.4 Conclusions. References.
• 8 Computational Modeling of Selective Pharmacophores at the a1-Adrenergic Receptors (Francesca Fanelli, Pier G. De Benedetti). 8.1 Introduction. 8.2 Ligand-Based and Receptor-Based Pharmacophore Modeling and QSAR Analysis. 8.3 The General 1-AR Pharmacophore. 8.4 Modeling the a1-AR Subtype Selectivities of Different Classes of Antagonists. 8.5 Antitarget Modeling of Biogenic Amine-Binding GPCRs: Common Features and Subtle Differences. 8.6 Conclusions. 8.7 Perspectives. References. III Antitargets: Cytochrome P450s and Transporters.
• 9 Cytochrome P450s: Drug-Drug Interactions (Dan Rock, Jan Wahlstrom, Larry Wienkers). 9.1 Introduction. 9.2 Reversible Inhibition. 9.3 Irreversible Inhibition. 9.4 Conclusion. References.
• 10 Site of Metabolism Predictions: Facts and Experiences (Ismael Zamora). 10.1 Introduction. 10.2 Factors That Influence the Site of Metabolism Prediction by Cytochrome P450s. 10.3 Methods to Predict the Site of Metabolism. 10.4 The Influence of the Protein Structure on the Site of Metabolism. 10.5 Conclusions. References.
• 11 Irreversible Cytochrome P450 Inhibition: Common Substructures and Implications for Drug Development (Sonia M. Poli). 11.1 Introduction. 11.2 Overview. 11.3 Structural Features Often Responsible for Mechanism-Based CYP Inhibition. 11.4 Conclusions. References.
• 12 MetaSite: Understanding CYP Antitarget Modeling for Early Toxicity Detection (Yasmin Aristei, Gabriele Cruciani, Sergio Clementi, Emanuele Carosati, Riccardo Vianello, Paolo Benedetti). 12.1 Introduction. 12.2 The CYPs as Antitarget Enzymes. 12.3 The UGTs as Antitarget Enzymes. 12.4 The MetaSite Technology. 12.5 Conclusions. 12.6 Software Package. References.
• 13 Orphan Nuclear Receptor PXR-Mediated Gene Regulation in Drug Metabolism and Endobiotic Homeostasis (Jie Zhou, Yonggong Zhai, Wen Xie). 13.1 Cloning and Initial Characterization of PXR. 13.2 PXR and Its Regulation of Drug-Metabolizing Enzymes and Transporters. 13.3 Crosstalk Between PXR and Other Nuclear Receptors. 13.4 Implications of PXR-Mediated Gene Regulation for Drug Metabolism and Pathophysiology. 13.5 Species Specificity of PXR and the Creation of "Humanized" Mice. 13.6 Conclusions. References.
• 14 Ligand Features Essential for Cytochrome P450 Induction (Daniela Schuster, Theodora M.Steindl, Thierry Langer). 14.1 Introduction. 14.2 Molecular Mechanisms Leading to P450 Induction. 14.3 General Ligand Features Leading to NR Activation. References.
• 15 Transporters and Drugs - An Overview (Hartmut Glaeser, Martin F. Fromm, Jorg Konig). 15.1 Introduction. 15.2 Organic Anion Transporting Polypeptides and Drug Transport. 15.3 Multidrug Resistance Proteins and Drug Transport. 15.4 Role of P-Glycoprotein for Drug Disposition. 15.5 Vectorial Drug Transport. References.
• 16 Computational Models for P-Glycoprotein Substrates and Inhibitors (Patrizia Crivori). 16.1 P-Glycoprotein Structure, Expression, Mechanism of Transport and Role on Drug Pharmacokinetics. 16.2 In Vitro Models for Studying P-gp Interacting Compounds. 16.3 Computational Models for Predicting P-gp Interacting Compounds. 16.4 Computational Models for Other Important Drug Transporters. 16.5 Conclusions. References. IV Case Studies of Drug Optimization Against Antitargets.
• 17 Selective Dipeptidyl Peptidase IV Inhibitors for the Treatment of Type 2 Diabetes: The Discovery of JANUVIA2 (Sitagliptin) (Scott D. Edmondson, Dooseop Kim). 17.1 Introduction. 17.2 Selectivity of DPP-4 Inhibitors. 17.3 a-Amino Acid Amide Series. 17.4 Early b-Amino Acid Amide DPP-4 Inhibitors. 17.5 Conclusions. References.
• 18 Strategy and Tactics for hERG Optimizations (Craig Jamieson, Elizabeth M. Moir, Zoran Rankovic, Grant Wishart). 18.1 Introduction. 18.2 Survey of Strategies Used to Diminish hERG. 18.3 Summary and Analysis. References.
• 19 Structure-Based In Silico Driven Optimization: Discovery of the Selective 5-HT1A Agonist PRX-00023 (Oren M. Becker). 19.1 Introduction. 19.2 Structure-Based In Silico Driven Multidimensional Optimization Paradigm. 19.3 Clinical Candidate Selection Criteria. 19.4 Lead Identification. 19.5 Optimization Round
• 1: Reducing Off-Target Activities. 19.6 Optimization Round
• 2: Reducing Affinity to hERG. 19.7 Conclusion. References. Index.
• (source: Nielsen Book Data)

This practice oriented handbook surveys current knowledge on the prediction and prevention of adverse drug reactions related to off target activity of small molecule drugs. It is unique in collating the current approaches into a single source, and includes several highly instructive case studies that may be used as guidelines on how to improve drug development projects. With its large section on ADME related effects, this is key knowledge for every drug developer.
(source: Nielsen Book Data)

• List of Contributors. Preface. A Personal Foreword. I Introduction.
• 1 A Fresh Look at Molecular Structure and Properties (Bernard Testa, Giulio Vistoli, and Alessandro Pedretti). 1.1 Introduction. 1.2 Core Features: The Molecular "Genotype". 1.3 Observable and Computable Properties: The Molecular "Phenotype". 1.4 Molecular Properties and their Adaptability: The Property Space of Molecular Entities. 1.5 Conclusions.
• 2 Physicochemical Properties in Drug Profiling (Han van de Waterbeemd). 2.1 Introduction. 2.2 Physicochemical Properties and Pharmacokinetics. 2.3 Dissolution and Solubility. 2.4 Ionization (pKa). 2.5 Molecular Size and Shape. 2.6 H-bonding. 2.7 Lipophilicity. 2.8 Permeability. 2.9 Amphiphilicity. 2.10 Drug-like Properties. 2.11 Computation versus Measurement of Physicochemical Properties. 2.12 Outlook. II Electronic Properties and H-Bonding.
• 3 Drug Ionization and Physicochemical Profiling (Alex Avdeef). 3.1 Introduction. 3.2 Accurate Determination of Ionization Constants. 3.3 "Octanol" and "Membrane" pKa in Partition Coefficients Measurement. 3.4 "Gibbs" and Other "Apparent" pKa in Solubility Measurement. 3.5 "Flux" and other "Apparent" pKa in Permeability Measurement. 3.6 Conclusions.
• 4 Electrotopological State Indices (Ovidiu Ivanciuc). 4.1 Introduction. 4.2 E-state Indices. 4.3 Application of E-State Indices in Medicinal Chemistry. 4.4 Conclusions and Outlook.
• 5 Polar Surface Area (Peter Ertl). 5.1 Introduction. 5.2 Application of PSA for Prediction of Drug Transport Properties. 5.3 Application of PSA in Virtual Screening. 5.4 Calculation of PSA. 5.5 Correlation of PSA with other Molecular Descriptors. 5.6 Conclusions.
• 6 H-bonding Parameterization in Quantitative Structure-Activity Relationships and Drug Design (Oleg Raevsky). 6.1 Introduction. 6.2 Two-dimensional H-bond Descriptors. 6.3 Three-dimensional H-bond Descriptors. 6.4 Application of H-bond Descriptors in QSAR Studies and Drug Design. 6.5 Conclusions. III Conformations.
• 7 Three-dimensional Structure Generation (Jens Sadowski). 7.1 Introduction. 7.2 Problem Description. 7.3 Concepts. 7.4 Practical Aspects. 7.5 Conclusions.
• 8 Exploiting Ligand Conformations in Drug Design (Jonas Bostrom and Andrew Grant). 8.1 Introduction. 8.2 Generating Relevant Conformational Ensembles. 8.3 Using Conformational Effects in Drug Design. 8.4 Conclusions.
• 9 Conformational Analysis of Drugs by Nuclear Magnetic Resonance Spectroscopy (Burkhard Luy, Andreas Frank, and Horst Kessler). 9.1 Introduction. 9.2 NMR Parameters for Conformational Analysis. 9.3 Conformation Bound to the Receptor. 9.4 Refi nement of Conformations by Computational Methods. IV Solubility.
• 10 Drug Solubility in Water and Dimethylsulfoxide (Christopher Lipinski). 10.1 Introduction. 10.2 Water Solubility. 10.3 Early Discovery Water Solubility and Biological Testing. 10.4 Water Solubility Measurement Technology. 10.5 Compound Ionization Properties. 10.6 Compound Solid-state Properties. 10.7 DMSO Solubility. 10.8 Conclusions.
• 11 Challenge of Drug Solubility Prediction (Andreas Klamt and Brian J Smith). 11.1 Importance of Aqueous Drug Solubility. 11.2 Thermodynamic States Relevant for Drug Solubility. 11.3 Prediction of DELTAGfus. 11.4 Prediction of Liquid Solubility with COSMO-RS. 11.5 Prediction of Liquid Solubility with Molecular Dynamics (MD) and Monte Carlo (MC) Methods. 11.6 Group-Group Interaction Methods. 11.7 Nonlinear Character of Log Sw. 11.8 QSPRs. 11.9 Experimental Solubility Datasets. 11.10 Atom Contribution Methods, Electrotopological State (E-state) Indices and GCMs. 11.11 Three-dimensional Geometry-based Models. 11.12 Conclusions and Outlook. V Lipophilicity.
• 12 Lipophilicity: Chemical Nature and Biological Relevance (Giulia Caron and Giuseppe Ermondi). 12.1 Chemical Nature of Lipophilicity. 12.2 Biological Relevance of Lipophilicity. 12.3 Conclusions.
• 13 Chromatographic Approaches for Measuring Log P (Sophie Martel, Davy Guillarme, Yveline Henchoz, Alexandra Galland, Jean-Luc Veuthey, Serge Rudaz, and Pierre-Alain Carrupt). 13.1 Introduction. 13.2 Lipophilicity Measurements by RPLC: Isocratic Conditions. 13.3 Lipophilicity Measurements by RPLC: Gradient Approaches. 13.4 Lipophilicity Measurements by Capillary Electrophoresis (CE). 13.5 Supplementary Material.
• 14 Prediction of Log P with Substructure-based Methods (Raimund Mannhold and Claude Ostermann). 14.1 Introduction. 14.2 Fragmental Methods. 14.3 Atom-based Methods. 14.4 Predictive Power of Substructure-based Approaches.
• 15 Prediction of Log P with Property-based Methods (Igor V. Tetko and Gennadiy I. Poda). 15.1 Introduction. 15.2 Methods Based on 3D Structure Representation. 15.3 Methods Based on Topological Descriptors. 15.4 Prediction Power of Property-based Approaches. 15.5 Conclusions.
• 16 The Good, the Bad and the Ugly of Distribution Coeffi cients: Current Status, Views and Outlook (Franco Lombardo, Bernard Faller, Marina Shalaeva, Igor Tetko, and Suzanne Tilton). 16.1 Log D and Log P. 16.2 Issues and Automation in the Determination of Log D. 16.3 pH-partition Theory and Ion-pairing. 16.4 Computational Approaches. 16.5 Some Concluding Remarks: The Good, the Bad and the Ugly. VI Drug- and Lead-likeness.
• 17 Properties Guiding Drug- and Lead-likeness (Sorel Muresan and Jens Sadowski). 17.1 Introduction. 17.2 Properties of Leads and Drugs. 17.3 Drug-likeness as a Classification Problem. 17.4 Application Example: Compound Acquisition. 17.5 Conclusions. Index.
• (source: Nielsen Book Data)

This first systematic overview for more than a decade is tailor made for the medicinal chemist. All the chapters are written by experienced drug developers and include practical examples from real drug candidates. Following an introduction to global drug properties and their impact on drug research, screening and combinatorial chemistry libraries, this handbook demonstrates the best and fastest way to estimate those properties most relevant for the efficiency and pharmacokinetic performance of a drug molecule: lipophilicity, solubility, electronic properties and conformation.
(source: Nielsen Book Data)

• Nuclear Receptors as Modern Drug Targets - a Historic Perspective Targeting the Nuclear Receptor - Cofactor Interaction Untangling the Estrogen Receptor Web Subtype Selective Estrogens Estrogen Receptors as Therapeutic Targets in Breast Cancer Progesterone Receptor and Progestines Progesterone Receptor Antagonists Nonsteroidal Tissue Selective Androgen Receptor Modulators The Glucocorticoid Receptor as Target for Classic and Novel Anti-inflammatory Therapy and Novel Glucocorticoid Receptor Ligands Vitamin D Analogs as Modulators of Vitamin D Receptor Action PPARs: Therapeutic Targets for Metabolic Disease and Type 2 Diabetes Retinoids in Clinical Use Nuclear Receptors as Targets in Cardiovascular Diseases NURR77 Family of Nuclear Receptors and its Modulators Induction of Drug Metabolism: The Role of Nuclear Receptors Nuclear Receptor Targeted Screening Libraries and Chemogenomics Approaches.
• (source: Nielsen Book Data)

Edited by two experts working at the pioneering pharmaceutical company and major global player in hormone-derived drugs, this handbook and reference systematically treats the drug development aspects of all human nuclear receptors, including recently characterized receptors such as PPAR, FXR and LXR. Authors from leading pharmaceutical companies around the world present examples and real-life data from their own work, in this book.
(source: Nielsen Book Data)

• PART I. INTRODUCTION.UNDERSTANDING STRUCTURAL DIAGRAMS OF ORGANIC MOLECULES.SOME COMMON MOLECULES.PROTEINS AND THREE-DIMENSIONAL PROTEIN STRUCTURE.SOME OF THE PROTEIN STRUCTURES THAT APPEAR IN THIS BOOK.PART II. INFLAMMATORY, CARDIOVASCULAR AND METABOLIC DISEASES.ANTI-INFLAMMATORY AGENTS.Acetylsalicylic acid Aspirin).Naproxen (Aleve).How Do Anti-Inflammatory Drugs Work?Other Eicosanoids in Inflammation.An Overview of Inflammation.Celecoxib (Celebrex).Prednisone (Deltasone).Methotrexate (Trexall).Allopurinol (Zyloprim).ANTIASTHMATIC AND ANTIALLERGIC AGENTS.Salmeterol (Serevent).Fluticasone Propionate (Flovent).Montelukast Sodium (Singulair).Tiotropium Bromide (Spiriva).Loratadine (Claritin).TYPE 2 DIABETES.An Overview of Metabolic Syndrome.ANTIDIABETIC AND CHOLESTEROL-LOWERING AGENTS.Metformin (Glucophage).Glipizide (Glucotrol).Pioglitazone (Actos).Sitagliptin (Januvia).Atorvastatin (Lipitor).Ezetimibe (Zetia).CARDIOVASCULAR AGENTS.Atenolol (Tenormin).Enalapril (Vasotec).Candesartan Cilexetil (Atacand).Aliskiren (Tekturna).Amlodipine (Norvasc).Nitroglycerin.Clopidogrel Bisulfate (Plavix).Digoxin (Lanoxin).RECEPTORS AND SIGNALING.Information Flow into the Cell by Chemical Signaling.REFERENCES FOR PART II.PART III. REPRODUCTIVE MEDICINE.Oral Contraceptives.Testosterone.Mifepristone (Mifeprex).Oxytocin (Oxytocin).Sildenafil (Viagra).OSTEOPOROSIS.Some Aspects of Osteoporosis.Alendronate (Fosamax).Calcitriol (Rocaltrol).Raloxifene (Evista).Teriparatide (Forteo).GLAUCOMA AND ANTIULCER AGENTS.Latanoprost (Xalatan).Ranitidine (Zantac).Omeprazole (Prilosec).REFERENCES FOR PART III.PART IV. AUTOIMMUNE DISEASE AND ORGAN TRANSPLANT.A Brief Survey of the Immune System.IMMUNOSUPPRESSIVE AGENTS.Azathioprine (Imuran).Mycophenolate Mofetil (CellCept).Cyclosporin (Neoral).Tacrolimus (Prograf).FTY720 (Fingolimod).INFECTIOUS DISEASES.ANTIBIOTICS.Amoxicillin (Amoxil).Cefaclor (Ceclor).Doxycycline (Vibramycin).Azithromycin (Zithromax).Ciprofloxacin (Cipro).Trimethoprim (Triprim).Amikacin (Amikin).Vancomycin (Vancocin).Linezolid (Zyvox).Isoniazid (Laniazid).Ancillary Antibiotics.Drug Resistance.ANTIVIRAL AGENTS.On Viruses and Viral Diseases.Acyclovir (Zovirax).Ribavirin (Virazole).Oseltamivir (Tamiflu).Zidovudine (Retrovir, AZT).Zalcitabine (Hivid).Nevirapine (Viramune).Efavirenz (Sustiva).Lopinavir + Ritonavir (Kaletra).UK427857 (Maraviroc).ANTIFUNGAL AGENTS.Amphotericin (Fungizone).Fluconazole (Diflucan).Caspofungin (Cancidas).Terbinafine (Lamisil).ANTIMALARIAL AND ANTIPARASITIC AGENTS.Parasitic Diseases: A Focus on Malaria.Chloroquine (Aralen).Artemether + Lumefantrine (CoArtem).Atovaquone + Proguanil (Malarone).Miltefosine (Impavido).Nitazoxanide (Alinia).Ivermectin (Stromectol).REFERENCES FOR PART IV.PART V. MALIGNANT DISEASE.An Overview of Cancer.Capecitabine (Xeloda).Carboplatin (Paraplatin).Vinblastine (Velban).Paclitaxel (Taxol).Cyclophosphamide (Cytoxan).Tamoxifen (Nolvadex).Irinotecan (Camptosar).Bleomycin (Blenoxane).Imatinib (Gleevec).Sunitinib (Sutent).Bortezomib (Velcade).Ancillary Anticancer Agents.REFERENCES FOR PART V.PART VI. DRUGS ACTING ON THE NERVOUS SYSTEM.PAIN AND ANALGESIA.Lidocaine (Xylocaine).Morphine (Avinza).Acetaminophen (Tylenol).Fentanyl (Duragesic).Sodium Thiopental (Sodium Pentothal).Gabapentin (Neurontin).Diazepam (Valium).Sumatriptan (Imitrex).HYPNOTICS (INSOMNIA) AND ANTISMOKING.Zolpidem (Ambien).Ramelteon (Rozerem).Varenicline (Chantix).The Brain, Neurotransmission and Molecular Neurotransmitters.NEURODEGENERATIVE AND PSYCHIATRIC DISEASES.Levodopa (Larodopa).Donepezil (Aricept).ANTIEPILEPTIC AGENTS.ANTIANXIETY AGENTS.ANTIDEPRESSANTS.ANTIPSYCHOTICS.REFERENCES FOR PART VI.GLOSSARY.INDEX.
• (source: Nielsen Book Data)

"Molecules and Medicine" provides, for the first time ever, a completely integrated look at chemistry, biology, drug discovery, and medicine. It delves into the discovery, application, and mode of action of more than one hundred of the most significant molecules in use in modern medicine. Opening sections of this book provide a unique, clear, and concise introduction, which enables readers to understand chemical formulas.
(source: Nielsen Book Data)

• Preface.
• 1. G Protein-coupled Receptors in the Human Genome (R. Fredriksson & H. Schioth).
• 2. Why G Protein-coupled Receptors Databases are Needed (J. Haiech, et al.).
• 3. A Novel Drug Screening Assay for G Protein-coupled Receptors (B. O'Dowd, et al.).
• 4. Importance of GPCR Dimerization for Function: The Case of the Class C GPCRs (L. Prezeau, et al.).
• 5. Molecular Mechanisms of GPCR Activation (R. Bywater & P. Denny-Gouldson).
• 6. Allosteric Properties and Regulation of G Protein-coupled Receptors (J. Galzi, et al.).
• 7. Chemogenomics Approaches to Ligand Design (T. Klabunde).
• 8. Strategies for the Design of pGPCR-targeted Libraries (N. Savchuk, et al.).
• 9. Ligand-based Rational Design: Virtual Screening (D. Clark & C. Higgs).
• 10. 3-D Structure of G Protein-coupled Receptors (L. Pardo, et al.).
• 11. 7TM Models in Structure-based Drug Design (F. Blaney, et al.).
• 12. Receptor-based Rational Design: Virtual Screening (D. Rognan). Subject Index.
• (source: Nielsen Book Data)

G protein-coupled receptors (GPCRs) are one of the most important target classes in pharmacology and are the target of many blockbuster drugs. Yet only with the recent elucidation of the rhodopsin structure have these receptors become amenable to a rational drug design. Based on recent examples from academia and the pharmaceutical industry, this book demonstrates how to apply the whole range of bioinformatics, chemoinformatics and molecular modeling tools to the rational design of novel drugs targeting GPCRs. This book is an essential reading for medicinal chemists and drug designers working with this largest class of drug targets in the human genome.
(source: Nielsen Book Data)

• Preface. Abbreviations and Symbols.
• 1. Physicochemistry. 1.1 Physicochemistry and Pharmacokinetics. 1.2 Partition and Distribution Coefficient as Measures of Lipophilicity. 1.3 Limitations on the Use of 1-Octanol. 1.4 Further Understanding of Log P. 1.4.1 Unravelling the Principal Contributions to Log P. 1.4.2 Hydrogen Bonding. 1.4.3 Molecular Size and Shape. 1.5 Alternative Lipophilicity Scales. 1.5.1 Different Solvent Systems. 1.5.2 Chromatographic Approaches. 1.5.3 Liposome Partitioning. 1.6 Computational Approaches to Lipophilicity. 1.7 Membrane Systems to Study Drug Behaviour. 1.8 Dissolution and Solubility. 1.8.1 Why Measure Solubility? 1.8.2 Calculated Solubility. 1.9 Ionisation (pKa).
• 2. Pharmacokinetics. 2.1 Setting the Scene. 2.2 Intravenous Administration: Volume of Distribution. 2.3 Intravenous Administration: Clearance. 2.4 Intravenous Administration: Clearance and Half-life. 2.5 Intravenous Administration: Infusion. 2.6 Oral Administration. 2.7 Repeated Doses. 2.8 Development of the Unbound (Free) Drug Model. 2.9 Unbound Drug and Drug Action. 2.10 Unbound Drug Model and Barriers to Equilibrium. 2.11 Slow Offset Compounds. 2.12 Factors Governing Unbound Drug Concentration.
• 3. Absorption. 3.1 The Absorption Process. 3.2 Dissolution. 3.3 Membrane Transfer. 3.4 Barriers to Membrane Transfer. 3.5 Models for Absorption Estimation. 3.6 Estimation of Absorption Potential. 3.7 Computational Approaches.
• 4. Distribution. 4.1 Membrane Transfer Access to the Target. 4.2 Brain Penetration. 4.3 Volume of Distribution and Duration. 4.4 Distribution and Tmax.
• 5. Clearance. 5.1 The Clearance Processes. 5.2 Role of Transport Proteins in Drug Clearance. 5.3 Interplay Between Metabolic and Renal Clearance. 5.4 Role of Lipophilicity in Drug Clearance.
• 6. Renal Clearance. 6.1 Kidney Anatomy and Function. 6.2 Lipophilicity and Reabsorption bu the Kidney. 6.3 Effect of Charge on renal Clearance. 6.4 Plasma Protein Binding and Renal Clearance. 6.5 Balancing Renal Clearance and Absorption. 6.6 Renal Clearance and Drug Design.
• 7. Metabolic (Hepatic) Clearance. 7.1 Function of Metabolism (Biotransformation). 7.2 Cytochrome. 7.2.1 Catalytic Selectivity of CYP2D6. 7.2.2 Catalytic Selectivity of CYP2C9. 7.2.3 Catalytic Selectivity of CYP3A4. 7.3 Other Oxidative Metabolism Processes. 7.4 Oxidative Metabolism and Drug Design. 7.5 Non-Specific Esterases. 7.5.1 Function of Esterases. 7.5.2 Ester Drugs as Intravenous and Topical Agents. 7.6 Prodrugs to Aid Membrane Transfer. 7.7 Enzymes Catalysing Drug Conjugation. 7.7.1 Glucuronyl and Sulpho-Transferases. 7.7.2 Methyl Transferases. 7.7.3 Glutathione S-Transferases. 7.8 Stability to Conjugation Processes. 7.9 Pharmacodynamics and Conjugation.
• 8. Toxicity. 8.1 Toxicity Findings. 8.1.1 Pharmacophore-induced Toxicity. 8.1.2 Structure-related Toxicity. 8.1.3 Metabolism-induced Toxicity. 8.2 Importance of Dose Size. 8.3 Expoxides. 8.4 Quinone Imines. 8.5 Nitrenium Ions. 8.6 Iminium Ions. 8.7 Hydroxylamines. 8.8 Thiophene Rings. 8.9 Thioureas. 8.10 Chloroquinolines. 8.11 Stratification of Toxicity. 8.12 Toxicity Prediction: Computational Toxicology. 8.13 Toxicogenomics. 8.14 Enzyme Induction (CYP3A4) and Drug Design. 8.15 Enzyme Inhibition and Drug Design.
• 9. Inter-Species Scaling. 9.1 Objectives of Inter-Species Scaling. 9.2 Allometric Scaling. 9.2.1 Volume of Distribution. 9.2.2 Clearance. 9.3 Species Scaling: Adjusting for Maximum Life Span Potential. 9.4 Species Scaling: Incorporating Differences in Metabolic Clearance. 9.5 Inter-Species Scaling for Clearance by Hepatic Uptake. 9.6 Elimination Half-Life. 9.7 Scaling to Pharmacological Effect. 9.8 Single Animal Scaling.
• 10. High(er) throughput ADME Studies. 10.1 The High-Throughput Screening (HTS) Trend. 10.2 Drug Metabolism and Discovery Screening Sequences. 10.3 Physicochemistry. 10.3.1 Solubility. 10.3.2 Lipophilicity. 10.4 Absorption/Permeability. 10.5 Pharmacokinetics. 10.6 Metabolism and Inhibition. 10.7 The Concept of ADME Space. 10.8 Computational Approaches in PK and Metabolism. 10.8.1 QSPR and QSMR. 10.8.2 PK Predictions Using QSAR and Neural Networks. 10.8.3 Is In Silico Meeting Medicinal chemistry Needs in ADME Prediction? 10.8.4 Physiologically-Based Pharmacolinetic (PBPK) Modelling. 10.9 Outlook. Index.
• (source: Nielsen Book Data)

The medical benefits of a drug are not only dependent on its biological effect, but also on its "life cycle" within the organism - from its absorption into the blood, distribution to tissue until its eventual breakdown or excretion by the liver and kidneys. Here, the authors, all of them employed at Pfizer in the discovery and development of new active substances, discuss the significant parameters and processes important for the absorption, distribution and retention of drug compounds in the body, plus the potential problems created by their transformation into toxic byproducts. The authors cover everything from the fundamental principles right up to the latest developments using high throughput methods to analyze the pharmacokinetic properties of active substances. Particular emphasis is placed on the impact of pharmacokinetic parameters on the discovery of new drugs - one of the most challenging tasks in global pharmaceutical research. Thus, this book is aimed at all those dealing professionally with the development and application of pharmaceutical substances. Furthermore, the readily comprehensible style of writing makes it equally suitable for students of pharmacy and related subjects, who feel that pharmacokinetics is covered too briefly in the standard textbooks.
(source: Nielsen Book Data)