Comprehensive medicinal chemistry II: 1 Global perspective
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| Format: | Electronic eBook |
|---|---|
| Language: | English |
| Published: |
Amsterdam [u.a.]
Elsevier
2007
|
| Edition: | 1. ed. |
| Online Access: | UBR01 Volltext Inhaltsverzeichnis |
| Physical Description: | 1 Online-Ressource |
| ISBN: | 0080445144 9780080445144 |
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| adam_text | Contents
Contents of all Volumes xi
Preface xix
Preface to Volume 1 xxi
Editors in Chief xxiii
Editor of Volume 1 xxiv
Contributors to Volume 1 xxv
Historical Perspective and Outlook
1.01 Reflections of a Medicinal Chemist: Formative Years through Thirty Seven Years
Service in the Pharmaceutical Industry 1
R F HIRSCHMANN, University of Pennsylvania, Philadelphia, PA, USA and
J L STURCHIO, Merck Co., Inc., White House Station, NJ, USA
1.02 Drug Discovery: Historical Perspective, Current Status, and Outlook 29
P W ERHARDT, University of Toledo, OH, USA and J R PROUDFOOT, Boehringer
Ingelheim Inc., Ridgefield, CT, USA
1.03 Major Drug Introductions 97
P D KENNEWELL, Swindon, UK
The Impact of New Genomic Technologies
1.04 Epigenetics 251
W W WEBER, University of Michigan, Ann Arbor, MI, USA
1.05 Personalized Medicine 279
D GURWITZ, Tel Aviv University, Tel Aviv, Israel and V G MANOLOPOULOS,
Democritus University of Thrace, Alexandroupolis, Greece
1.06 Gene Therapy 297
M THANOU, Imperial College London, London, UK, and S WADD1NGTON,
University College London, London, UK, and A D MILLER, Imperial College London,
London, UK
Contents
Sources of New Drugs
1.07 Overview of Sources of New Drugs 321
D BROWN, Alchemy Biomedieal Consulting, Cambridge, UK
1.08 Natural Product Sources of Drugs: Plants, Microbes, Marine Organisms, and
Animals 355
G M CRAGG and D J NEWMAN, NCI, Frederick, MD, USA
1.09 Traditional Medicines 405
L A MITSCHER, University of Kansas, Lawrence, KS, USA
1.10 Biological Macromolecules 431
J K OSBOURN, Cambridge Antibody Technology, Cambridge, UK
1.11 Nutraceuticals 449
P A LACHANCE and Y T DAS, Rutgers The State University of New Jersey,
New Brunswick, NJ, USA
Animal Experimentation
1.12 Alternatives to Animal Testing 463
R D COMBES, FRAME, Nottingham, UK
The Role of Industry
1.13 The Role of Small or Medium Sized Enterprises in Drug Discovery 489
C G NEWTON, BioFocus DRI, Saffron Walden, UK
1.14 The Role of the Pharmaceutical Industry 527
R BARKER, Association of the British Pharmaceutical Industry (ABPI), London, UK
and M DARNBROUGH, London, UK
1.15 The Role of the Venture Capitalist 553
D J BOWER, University of Dundee, Scotland, UK
1.16 Industry Academic Relationships 571
M DARNBROUGH, London, UK and M SKINGLE, GlaxoSmithKline,
Stevenage, UK
Drug Discovery: Revolution, Decline?
1.17 Is the Biotechnology Revolution a Myth? 591
M M HOPKINS, University of Sussex, Brighton, UK, and A KRAFT and
P A MARTIN, Nottingham University, Nottingham, UK, and P NIGHTINGALE and
S MAHDI, University of Sussex, Brighton, UK
1.18 The Apparent Declining Efficiency of Drug Discovery 615
D TRIST, E RATTI, and L DA ROS, GlaxoSmithKline, Verona, Italy
Healthcare in the Social Context
1.19 How Much is Enough or Too Little: Assessing Healthcare Demand in Developed
Countries 627
D CALLAHAN, The Hastings Center, Garrison, NY, USA
1.20 Health Demands in Developing Countries 637
A A WASUNNA, The Hastings Center, Garrison, NY, USA
1.21 Orphan Drugs and Generics 655
C P MILNE and L A CABANILLA, Tufts University, Boston, MA, USA
Contents ix
Ethical Issues
1.22 Bioethical Issues in Medicinal Chemistry and Drug Treatment 681
P R WOLPE, University of Pennsylvania, Philadelphia, PA, USA, and M SAHL,
MJSahl Consulting, Philadelphia, PA, USA, and J R HOWARD, University of
Pennsylvania, Philadelphia, PA, USA
1.23 Ethical Issues and Challenges Facing the Pharmaceutical Industry 709
M L EATON, Stanford University, Graduate School of Business, Stanford, CA, USA
Funding and Regulation of Research
1.24 The Role of Government in Health Research 725
J K OZAWA, SRI International, Arlington, VA, USA and Q C FRANCO, Strut Edge,
Washington, DC, USA
1.25 Postmarketing Surveillance 755
A LI WAN PO, Centre for Evidence Based Pharmacotherapv, Nottingham, UK
Intellectual Property
1.26 Intellectual Property Rights and Patents 779
J COCKBAIN, Frank B Dehn Co, Oxford, UK
Subject Index 817
Contents of all Volumes
Volume 1 Global Perspective
Historical Perspective and Outlook
1.01 Reflections of a Medicinal Chemist: Formative Years through Thirty Seven Years Service in
the Pharmaceutical Industry
1.02 Drug Discovery: Historical Perspective, Current Status, and Outlook
1.03 Major Drug Introductions
The Impact of New Genomic Technologies
1.04 Epigenetics
1.05 Personalized Medicine
1.06 Gene Therapy
Sources of New Drugs
1.07 Overview of Sources of New Drugs
1.08 Natural Product Sources of Drugs: Plants, Microbes, Marine Organisms, and Animals
1.09 Traditional Medicines
1.10 Biological Macromolecules
1.11 Nutraceuticals
Animal Experimentation
1.12 Alternatives to Animal Testing
The Role of Industry
1.13 The Role of Small or Medium Sized Enterprises in Drug Discovery
1.14 The Role of the Pharmaceutical Industry
1.15 The Role of the Venture Capitalist
1.16 Industry Academic Relationships
Drug Discovery: Revolution, Decline?
1.17 Is the Biotechnology Revolution a Myth?
1.18 The Apparent Declining Efficiency of Drug Discovery
Healthcare in the Social Context
1.19 How Much is Enough or Too Little: Assessing Healthcare Demand in Developed Countries
1.20 Health Demands in Developing Countries
1.21 Orphan Drugs and Generics
Ethical Issues
1.22 Bioethical Issues in Medicinal Chemistry and Drug Treatment
1.23 Ethical Issues and Challenges Facing the Pharmaceutical Industry
Funding and Regulation of Research
1.24 The Role of Government in Health Research
1.25 Postmarketing Surveillance
Contents of all Volumes
Intellectual Property
1.26 Intellectual Property Rights and Patents
Subject Index
Volume 2 Strategy and Drug Research
Introduction
2.01 The Intersection of Strategy and Drug Research
2.02 An Academic Perspective
2.03 An Industry Perspective
Organizational Aspects and Strategies for Drug Discovery and Development
2.04 Project Management
2.05 The Role of the Chemical Development, Quality, and Regulatory Affairs Teams in Turning a
Potent Agent into a Registered Product
2.06 Drug Development
2.07 In House or Out Source
2.08 Pharma versus Biotech: Contracts, Collaborations, and Licensing
2.09 Managing Scientists, Leadership Strategies in Science
2.10 Innovation (Fighting against the Current)
2.11 Enabling Technologies in Drug Discovery: The Technical and Cultural Integration of the
New with the Old
2.12 How and Why to Apply the Latest Technology
2.13 How and When to Apply Absorption, Distribution, Metabolism, Excretion, and Toxicity
2.14 Peptide and Protein Drugs: Issues and Solutions
2.15 Peptidomimetic and Nonpeptide Drug Discovery: Receptor, Protease, and Signal
Transduction Therapeutic Targets
2.16 Bioisosterism
2.17 Chiral Drug Discovery and Development From Concept Stage to Market Launch
2.18 Promiscuous Ligands
Targets
2.19 Diversity versus Focus in Choosing Targets and Therapeutic Areas
2.20 G Protein Coupled Receptors
2.21 Ion Channels Voltage Gated
2.22 Ion Channels Ligand Gated
2.23 Phosphodiesterases
2.24 Protein Kinases and Protein Phosphatases in Signal Transduction Pathways
2.25 Nuclear Hormone Receptors
2.26 Nucleic Acids (Deoxyribonucleic Acid and Ribonucleic Acid)
2.27 Redox Enzymes
List of Abbreviations
List of Symbols
Subject Index
Volume 3 Drug Discovery Technologies
Target Search
3.01 Genomics
3.02 Proteomics
3.03 Pharmacogenomics
3.04 Biomarkers
3.05 Microarrays
3.06 Recombinant Deoxyribonucleic Acid and Protein Expression
3.07 Chemical Biology
Contents of all Volumes xiii
Target Validation
3.08 Genetically Engineered Animals
3.09 Small Interfering Ribonucleic Acids
3.10 Signaling Chains
3.11 Orthogonal Ligand Receptor Pairs
Informatics and Databases
3.12 Chemoinformatics
3.13 Chemical Information Systems and Databases
3.14 Bioactivity Databases
3.15 Bioinformatics
3.16 Gene and Protein Sequence Databases
3.17 The Research Collaboratory for Structural Bioinformatics Protein Data Bank
3.18 The Cambridge Crystallographic Database
Structural Biology
3.19 Protein Production for Three Dimensional Structural Analysis
3.20 Protein Crystallization
3.21 Protein Crystallography
3.22 Bio Nuclear Magnetic Resonance
3.23 Protein Three Dimensional Structure Validation
3.24 Problems of Protein Three Dimensional Structures
3.25 Structural Genomics
Screening
3.26 Compound Storage and Management
3.27 Optical Assays in Drug Discovery
3.28 Fluorescence Screening Assays
3.29 Cell Based Screening Assays
3.30 Small Animal Test Systems for Screening
3.31 Imaging
3.32 High Throughput and High Content Screening
Chemical Technologies
3.33 Combinatorial Chemistry
3.34 Solution Phase Parallel Chemistry
3.35 Polymer Supported Reagents and Scavengers in Synthesis
3.36 Microwave Assisted Chemistry
3.37 High Throughput Purification
Lead Search and Optimization
3.38 Protein Crystallography in Drug Discovery
3.39 Nuclear Magnetic Resonance in Drug Discovery
3.40 Chemogenomics
3.41 Fragment Based Approaches
3.42 Dynamic Ligand Assembly
Subject Index
Volume 4 Computer Assisted Drug Design
Introduction to Computer Assisted Drug Design
4.01 Introduction to the Volume and Overview of Computer Assisted Drug Design in the Drug
Discovery Process
4.02 Introduction to Computer Assisted Drug Design Overview and Perspective for the Future
4.03 Quantitative Structure Activity Relationship A Historical Perspective and the Future
4.04 Structure Based Drug Design A Historical Perspective and the Future
Contents of all Volumes
Core Concepts and Methods Ligand Based
4.05 Ligand Based Approaches: Core Molecular Modeling
4.06 Pharmacophore Modeling: 1 Methods
4.07 Predictive Quantitative Structure Activity Relationship Modeling
4.08 Compound Selection Using Measures of Similarity and Dissimilarity
Core Concepts and Methods Target Structure Based
4.09 Structural, Energetic, and Dynamic Aspects of Ligand Receptor Interactions
4.10 Comparative Modeling of Drug Target Proteins
4.11 Characterization of Protein Binding Sites and Ligands Using Molecular Interaction Fields
4.12 Docking and Scoring
4.13 De Novo Design
Core Methods and Applications Ligand and Structure Based
4.14 Library Design: Ligand and Structure Based Principles for Parallel and Combinatorial
Libraries
4.15 Library Design: Reactant and Product Based Approaches
4.16 Quantum Mechanical Calculations in Medicinal Chemistry: Relevant Method or a Quantum
Leap Too Far?
Applications to Drug Discovery Lead Discovery
4.17 Chemogenomics in Drug Discovery The Druggable Genome and Target Class Properties
4.18 Lead Discovery and the Concepts of Complexity and Lead Likeness in the Evolution of
Drug Candidates
4.19 Virtual Screening
4.20 Screening Library Selection and High Throughput Screening Analysis/Triage
Applications to Drug Discovery Ligand Based Lead Optimization
4.21 Pharmacophore Modeling: 2 Applications
4.22 Topological Quantitative Structure Activity Relationship Applications: Structure
Information Representation in Drug Discovery
4.23 Three Dimensional Quantitative Structure Activity Relationship: The State of the Art
Applications to Drug Discovery Target Structure Based
4.24 Structure Based Drug Design The Use of Protein Structure in Drug Discovery
4.25 Applications of Molecular Dynamics Simulations in Drug Design
4.26 Seven Transmembrane G Protein Coupled Receptors: Insights for Drug Design from
Structure and Modeling
4.27 Ion Channels: Insights for Drug Design from Structure and Modeling
4.28 Nuclear Hormone Receptors: Insights for Drug Design from Structure and Modeling
4.29 Enzymes: Insights for Drug Design from Structure
New Directions
4.30 Multiobjective/Multicriteria Optimization and Decision Support in Drug Discovery
4.31 New Applications for Structure Based Drug Design
4.32 Biological Fingerprints
Subject Index
Volume 5 ADME Tox Approaches
Introduction
5.01 The Why and How of Absorption, Distribution, Metabolism, Excretion, and Toxicity
Research
Biological and In Vivo Aspects of Absorption, Distribution, Metabolism, Excretion, and Toxicity
5.02 Clinical Pharmacokinetic Criteria for Drug Research
5.03 In Vivo Absorption, Distribution, Metabolism, and Excretion Studies in Discovery and
Development
5.04 The Biology and Function of Transporters
5.05 Principles of Drug Metabolism 1: Redox Reactions
Contents of all Volumes XV
5.06 Principles of Drug Metabolism 2: Hydrolysis and Conjugation Reactions
5.07 Principles of Drug Metabolism 3: Enzymes and Tissues
5.08 Mechanisms of Toxification and Detoxification which Challenge Drug Candidates and
Drugs
5.09 Immunotoxicology
Biological In Vitro Tools in Absorption, Distribution, Metabolism, Excretion, and Toxicity
5.10 In Vitro Studies of Drug Metabolism
5.11 Passive Permeability and Active Transport Models for the Prediction of Oral Absorption
5.12 Biological In Vitro Models for Absorption by Nonoral Routes
5.13 In Vitro Models for Examining and Predicting Brain Uptake of Drugs
5.14 In Vitro Models for Plasma Binding and Tissue Storage
5.15 Progress in Bioanalytics and Automation Robotics for Absorption, Distribution,
Metabolism, and Excretion Screening
Physicochemical tools in Absorption, Distribution, Metabolism, Excretion, and Toxicity
5.16 Ionization Constants and Ionization Profiles
5.17 Dissolution and Solubility
5.18 Lipophilicity, Polarity, and Hydrophobicity
5.19 Artificial Membrane Technologies to Assess Transfer and Permeation of Drugs in
Drug Discovery
5.20 Chemical Stability
5.21 Solid State Physicochemistry
In Silico Tools in Absorption, Distribution, Metabolism, Excretion, and Toxicity
5.22 Use of Molecular Descriptors for Absorption, Distribution, Metabolism, and Excretion
Predictions
5.23 Electrotopological State Indices to Assess Molecular and Absorption, Distribution, Metabolism,
Excretion, and Toxicity Properties
5.24 Molecular Fields to Assess Recognition Forces and Property Spaces
5.25 In Silico Prediction of Ionization
5.26 In Silico Predictions of Solubility
5.27 Rule Based Systems to Predict Lipophilicity
5.28 In Silico Models to Predict Oral Absorption
5.29 In Silico Prediction of Oral Bioavailability
5.30 In Silico Models to Predict Passage through the Skin and Other Barriers
5.31 In Silico Models to Predict Brain Uptake
5.32 In Silico Models for Interactions with Transporters
5.33 Comprehensive Expert Systems to Predict Drug Metabolism
5.34 Molecular Modeling and Quantitative Structure Activity Relationship of Substrates and
Inhibitors of Drug Metabolism Enzymes
5.35 Modeling and Simulation of Pharmacokinetic Aspects of Cytochrome P450 Based Metabolic
Drug Drug Interactions
5.36 In Silico Prediction of Plasma and Tissue Protein Binding
5.37 Physiologically Based Models to Predict Human Pharmacokinetic Parameters
5.38 Mechanism Based Pharmacokinetic Pharmacodynamic Modeling for the Prediction of
In Vivo Drug Concentration Effect Relationships Application in Drug Candidate
Selection and Lead Optimization
5.39 Computational Models to Predict Toxicity
5.40 In Silico Models to Predict QT Prolongation
5.41 The Adaptive In Combo Strategy
Enabling Absorption, Distribution, Metabolism, Excretion, and Toxicity Strategies and Technologies in
Early Development
5.42 The Biopharmaceutics Classification System
5.43 Metabonomics
Contents of all Volumes
5.44 Prodrug Objectives and Design
5.45 Drug Polymer Conjugates
List of Abbreviations
List of Symbols
Subject Index
Volume 6 Therapeutic Areas I: Central Nervous System, Pain, Metabolic Syndrome, Urology,
Gastrointestinal and Cardiovascular
Central Nervous System
6.01 Central Nervous System Drugs Overview
6.02 Schizophrenia
6.03 Affective Disorders: Depression and Bipolar Disorders
6.04 Anxiety
6.05 Attention Deficit Hyperactivity Disorder
6.06 Sleep
6.07 Addiction
6.08 Neurodegeneration
6.09 Neuromuscular/Autoimmune Disorders
6.10 Stroke/Traumatic Brain and Spinal Cord Injuries
6.11 Epilepsy
6.12 Ophthalmic Agents
Pain
6.13 Pain Overview
6.14 Acute and Neuropathic Pain
6.15 Local and Adjunct Anesthesia
6.16 Migraine
Obesity/Metabolic Disorders/Syndrome X
6.17 Obesity/Metabolic Syndrome Overview
6.18 Obesity/Disorders of Energy
6.19 Diabetes/Syndrome X
6.20 Atherosclerosis/Lipoprotein/Cholesterol Metabolism
6.21 Bone, Mineral, Connective Tissue Metabolism
6.22 Hormone Replacement
Urogenital
6.23 Urogenital Diseases/Disorders, Sexual Dysfunction and Reproductive
Medicine: Overview
6.24 Incontinence (Benign Prostatic Hyperplasia/Prostate Dysfunction)
6.25 Renal Dysfunction in Hypertension and Obesity
Gastrointestinal
6.26 Gastrointestinal Overview
6.27 Gastric and Mucosal Ulceration
6.28 Inflammatory Bowel Disease
6.29 Irritable Bowel Syndrome
6.30 Emesis Prokinetic Agents
Cardiovascular
6.31 Cardiovascular Overview
6.32 Hypertension
6.33 Antiarrhythmics
6.34 Thrombolytics
Subject Index
Contents of all Volumes xvii
Volume 7 Therapeutic Areas II: Cancer, Infectious Diseases, Inflammation Immunology and
Dermatology
And Cancer
7.01 Cancer Biology
7.02 Principles of Chemotherapy and Pharmacology
7.03 Antimetabolites
7.04 Microtubule Targeting Agents
7.05 Deoxyribonucleic Acid Topoisomerase Inhibitors
7.06 Alkylating and Platinum Antitumor Compounds
7.07 Endocrine Modulating Agents
7.08 Kinase Inhibitors for Cancer
7.09 Recent Development in Novel Anticancer Therapies
Anti Viral
7.10 Viruses and Viral Diseases
7.11 Deoxyribonucleic Acid Viruses: Antivirals for Herpesviruses and Hepatitis B Virus
7.12 Ribonucleic Acid Viruses: Antivirals for Human Immunodeficiency Virus
7.13 Ribonucleic Acid Viruses: Antivirals for Influenza A and B, Hepatitis C Virus, and
Respiratory Syncytial Virus
Anti Fungal
7.14 Fungi and Fungal Disease
7.15 Major Antifungal Drugs
Anti Bacterials
7.16 Bacteriology, Major Pathogens, and Diseases
7.17 (3 Lactam Antibiotics
7.18 Macrolide Antibiotics
7.19 Quinolone Antibacterial Agents
7.20 The Antibiotic and Nonantibiotic Tetracyclines
7.21 Aminoglycosides Antibiotics
7.22 Anti Gram Positive Agents of Natural Product Origins
7.23 Oxazolidinone Antibiotics
7.24 Antimycobacterium Agents
7.25 Impact of Genomics Emerging Targets for Antibacterial Therapy
Drugs for Parasitic Infections
7.26 Overview of Parasitic Infections
7.27 Advances in the Discovery of New Antimalarials
7.28 Antiprotozoal Agents (African Trypanosomiasis. Chagas Disease, and Leishmaniasis)
I and I Diseases
7.29 Recent Advances in Inflammatory and Immunologieal Diseases: Focus on Arthritis Therapy
7.30 Asthma and Chronic Obstructive Pulmonary Disease
7.31 Treatment of Transplantation Rejection and Multiple Sclerosis
Dermatology
7.32 Overview of Dermatological Diseases
7.33 Advances in the Discovery of Acne and Rosacea Treatments
7.34 New Treatments for Psoriasis and Atopic Dermatitis
Subject Index
Volume 8 Case Histories and Cumulative Subject Index
Personal Essays
8.01 Introduction
8.02 Reflections on Medicinal Chemistry Since the 1950s
Contents of all Volumes
8.03 Medicinal Chemistry as a Scientific Discipline in Industry and Academia: Some Personal
Reflections
8.04 Some Aspects of Medicinal Chemistry at the Schering Plough Research Institute
Case Histories
8.05 Viread
8.06 Hepsera
8.07 Ezetimibe
8.08 Tamoxifen
8.09 Raloxifene
8.10 Duloxetine
8.11 Carvedilol
8.12 Modafinil, A Unique Wake Promoting Drug: A Serendipitous Discovery in Search of a
Mechanism of Action
8.13 Zyvox
8.14 Copaxone
8.15 Ritonavir and Lopinavir/Ritonavir
8.16 Fosamax
8.17 Omeprazole
8.18 Calcium Channel oc2 5 Ligands: Gabapentin and Pregabalin
Cumulative Subject Index
|
| adam_txt |
Contents
Contents of all Volumes xi
Preface xix
Preface to Volume 1 xxi
Editors in Chief xxiii
Editor of Volume 1 xxiv
Contributors to Volume 1 xxv
Historical Perspective and Outlook
1.01 Reflections of a Medicinal Chemist: Formative Years through Thirty Seven Years
Service in the Pharmaceutical Industry 1
R F HIRSCHMANN, University of Pennsylvania, Philadelphia, PA, USA and
J L STURCHIO, Merck Co., Inc., White House Station, NJ, USA
1.02 Drug Discovery: Historical Perspective, Current Status, and Outlook 29
P W ERHARDT, University of Toledo, OH, USA and J R PROUDFOOT, Boehringer
Ingelheim Inc., Ridgefield, CT, USA
1.03 Major Drug Introductions 97
P D KENNEWELL, Swindon, UK
The Impact of New Genomic Technologies
1.04 Epigenetics 251
W W WEBER, University of Michigan, Ann Arbor, MI, USA
1.05 Personalized Medicine 279
D GURWITZ, Tel Aviv University, Tel Aviv, Israel and V G MANOLOPOULOS,
Democritus University of Thrace, Alexandroupolis, Greece
1.06 Gene Therapy 297
M THANOU, Imperial College London, London, UK, and S WADD1NGTON,
University College London, London, UK, and A D MILLER, Imperial College London,
London, UK
Contents
Sources of New Drugs
1.07 Overview of Sources of New Drugs 321
D BROWN, Alchemy Biomedieal Consulting, Cambridge, UK
1.08 Natural Product Sources of Drugs: Plants, Microbes, Marine Organisms, and
Animals 355
G M CRAGG and D J NEWMAN, NCI, Frederick, MD, USA
1.09 Traditional Medicines 405
L A MITSCHER, University of Kansas, Lawrence, KS, USA
1.10 Biological Macromolecules 431
J K OSBOURN, Cambridge Antibody Technology, Cambridge, UK
1.11 Nutraceuticals 449
P A LACHANCE and Y T DAS, Rutgers The State University of New Jersey,
New Brunswick, NJ, USA
Animal Experimentation
1.12 Alternatives to Animal Testing 463
R D COMBES, FRAME, Nottingham, UK
The Role of Industry
1.13 The Role of Small or Medium Sized Enterprises in Drug Discovery 489
C G NEWTON, BioFocus DRI, Saffron Walden, UK
1.14 The Role of the Pharmaceutical Industry 527
R BARKER, Association of the British Pharmaceutical Industry (ABPI), London, UK
and M DARNBROUGH, London, UK
1.15 The Role of the Venture Capitalist 553
D J BOWER, University of Dundee, Scotland, UK
1.16 Industry Academic Relationships 571
M DARNBROUGH, London, UK and M SKINGLE, GlaxoSmithKline,
Stevenage, UK
Drug Discovery: Revolution, Decline?
1.17 Is the Biotechnology Revolution a Myth? 591
M M HOPKINS, University of Sussex, Brighton, UK, and A KRAFT and
P A MARTIN, Nottingham University, Nottingham, UK, and P NIGHTINGALE and
S MAHDI, University of Sussex, Brighton, UK
1.18 The Apparent Declining Efficiency of Drug Discovery 615
D TRIST, E RATTI, and L DA ROS, GlaxoSmithKline, Verona, Italy
Healthcare in the Social Context
1.19 How Much is Enough or Too Little: Assessing Healthcare Demand in Developed
Countries 627
D CALLAHAN, The Hastings Center, Garrison, NY, USA
1.20 Health Demands in Developing Countries 637
A A WASUNNA, The Hastings Center, Garrison, NY, USA
1.21 Orphan Drugs and Generics 655
C P MILNE and L A CABANILLA, Tufts University, Boston, MA, USA
Contents ix
Ethical Issues
1.22 Bioethical Issues in Medicinal Chemistry and Drug Treatment 681
P R WOLPE, University of Pennsylvania, Philadelphia, PA, USA, and M SAHL,
MJSahl Consulting, Philadelphia, PA, USA, and J R HOWARD, University of
Pennsylvania, Philadelphia, PA, USA
1.23 Ethical Issues and Challenges Facing the Pharmaceutical Industry 709
M L EATON, Stanford University, Graduate School of Business, Stanford, CA, USA
Funding and Regulation of Research
1.24 The Role of Government in Health Research 725
J K OZAWA, SRI International, Arlington, VA, USA and Q C FRANCO, Strut Edge,
Washington, DC, USA
1.25 Postmarketing Surveillance 755
A LI WAN PO, Centre for Evidence Based Pharmacotherapv, Nottingham, UK
Intellectual Property
1.26 Intellectual Property Rights and Patents 779
J COCKBAIN, Frank B Dehn Co, Oxford, UK
Subject Index 817
Contents of all Volumes
Volume 1 Global Perspective
Historical Perspective and Outlook
1.01 Reflections of a Medicinal Chemist: Formative Years through Thirty Seven Years Service in
the Pharmaceutical Industry
1.02 Drug Discovery: Historical Perspective, Current Status, and Outlook
1.03 Major Drug Introductions
The Impact of New Genomic Technologies
1.04 Epigenetics
1.05 Personalized Medicine
1.06 Gene Therapy
Sources of New Drugs
1.07 Overview of Sources of New Drugs
1.08 Natural Product Sources of Drugs: Plants, Microbes, Marine Organisms, and Animals
1.09 Traditional Medicines
1.10 Biological Macromolecules
1.11 Nutraceuticals
Animal Experimentation
1.12 Alternatives to Animal Testing
The Role of Industry
1.13 The Role of Small or Medium Sized Enterprises in Drug Discovery
1.14 The Role of the Pharmaceutical Industry
1.15 The Role of the Venture Capitalist
1.16 Industry Academic Relationships
Drug Discovery: Revolution, Decline?
1.17 Is the Biotechnology Revolution a Myth?
1.18 The Apparent Declining Efficiency of Drug Discovery
Healthcare in the Social Context
1.19 How Much is Enough or Too Little: Assessing Healthcare Demand in Developed Countries
1.20 Health Demands in Developing Countries
1.21 Orphan Drugs and Generics
Ethical Issues
1.22 Bioethical Issues in Medicinal Chemistry and Drug Treatment
1.23 Ethical Issues and Challenges Facing the Pharmaceutical Industry
Funding and Regulation of Research
1.24 The Role of Government in Health Research
1.25 Postmarketing Surveillance
Contents of all Volumes
Intellectual Property
1.26 Intellectual Property Rights and Patents
Subject Index
Volume 2 Strategy and Drug Research
Introduction
2.01 The Intersection of Strategy and Drug Research
2.02 An Academic Perspective
2.03 An Industry Perspective
Organizational Aspects and Strategies for Drug Discovery and Development
2.04 Project Management
2.05 The Role of the Chemical Development, Quality, and Regulatory Affairs Teams in Turning a
Potent Agent into a Registered Product
2.06 Drug Development
2.07 In House or Out Source
2.08 Pharma versus Biotech: Contracts, Collaborations, and Licensing
2.09 Managing Scientists, Leadership Strategies in Science
2.10 Innovation (Fighting against the Current)
2.11 Enabling Technologies in Drug Discovery: The Technical and Cultural Integration of the
New with the Old
2.12 How and Why to Apply the Latest Technology
2.13 How and When to Apply Absorption, Distribution, Metabolism, Excretion, and Toxicity
2.14 Peptide and Protein Drugs: Issues and Solutions
2.15 Peptidomimetic and Nonpeptide Drug Discovery: Receptor, Protease, and Signal
Transduction Therapeutic Targets
2.16 Bioisosterism
2.17 Chiral Drug Discovery and Development From Concept Stage to Market Launch
2.18 Promiscuous Ligands
Targets
2.19 Diversity versus Focus in Choosing Targets and Therapeutic Areas
2.20 G Protein Coupled Receptors
2.21 Ion Channels Voltage Gated
2.22 Ion Channels Ligand Gated
2.23 Phosphodiesterases
2.24 Protein Kinases and Protein Phosphatases in Signal Transduction Pathways
2.25 Nuclear Hormone Receptors
2.26 Nucleic Acids (Deoxyribonucleic Acid and Ribonucleic Acid)
2.27 Redox Enzymes
List of Abbreviations
List of Symbols
Subject Index
Volume 3 Drug Discovery Technologies
Target Search
3.01 Genomics
3.02 Proteomics
3.03 Pharmacogenomics
3.04 Biomarkers
3.05 Microarrays
3.06 Recombinant Deoxyribonucleic Acid and Protein Expression
3.07 Chemical Biology
Contents of all Volumes xiii
Target Validation
3.08 Genetically Engineered Animals
3.09 Small Interfering Ribonucleic Acids
3.10 Signaling Chains
3.11 Orthogonal Ligand Receptor Pairs
Informatics and Databases
3.12 Chemoinformatics
3.13 Chemical Information Systems and Databases
3.14 Bioactivity Databases
3.15 Bioinformatics
3.16 Gene and Protein Sequence Databases
3.17 The Research Collaboratory for Structural Bioinformatics Protein Data Bank
3.18 The Cambridge Crystallographic Database
Structural Biology
3.19 Protein Production for Three Dimensional Structural Analysis
3.20 Protein Crystallization
3.21 Protein Crystallography
3.22 Bio Nuclear Magnetic Resonance
3.23 Protein Three Dimensional Structure Validation
3.24 Problems of Protein Three Dimensional Structures
3.25 Structural Genomics
Screening
3.26 Compound Storage and Management
3.27 Optical Assays in Drug Discovery
3.28 Fluorescence Screening Assays
3.29 Cell Based Screening Assays
3.30 Small Animal Test Systems for Screening
3.31 Imaging
3.32 High Throughput and High Content Screening
Chemical Technologies
3.33 Combinatorial Chemistry
3.34 Solution Phase Parallel Chemistry
3.35 Polymer Supported Reagents and Scavengers in Synthesis
3.36 Microwave Assisted Chemistry
3.37 High Throughput Purification
Lead Search and Optimization
3.38 Protein Crystallography in Drug Discovery
3.39 Nuclear Magnetic Resonance in Drug Discovery
3.40 Chemogenomics
3.41 Fragment Based Approaches
3.42 Dynamic Ligand Assembly
Subject Index
Volume 4 Computer Assisted Drug Design
Introduction to Computer Assisted Drug Design
4.01 Introduction to the Volume and Overview of Computer Assisted Drug Design in the Drug
Discovery Process
4.02 Introduction to Computer Assisted Drug Design Overview and Perspective for the Future
4.03 Quantitative Structure Activity Relationship A Historical Perspective and the Future
4.04 Structure Based Drug Design A Historical Perspective and the Future
Contents of all Volumes
Core Concepts and Methods Ligand Based
4.05 Ligand Based Approaches: Core Molecular Modeling
4.06 Pharmacophore Modeling: 1 Methods
4.07 Predictive Quantitative Structure Activity Relationship Modeling
4.08 Compound Selection Using Measures of Similarity and Dissimilarity
Core Concepts and Methods Target Structure Based
4.09 Structural, Energetic, and Dynamic Aspects of Ligand Receptor Interactions
4.10 Comparative Modeling of Drug Target Proteins
4.11 Characterization of Protein Binding Sites and Ligands Using Molecular Interaction Fields
4.12 Docking and Scoring
4.13 De Novo Design
Core Methods and Applications Ligand and Structure Based
4.14 Library Design: Ligand and Structure Based Principles for Parallel and Combinatorial
Libraries
4.15 Library Design: Reactant and Product Based Approaches
4.16 Quantum Mechanical Calculations in Medicinal Chemistry: Relevant Method or a Quantum
Leap Too Far?
Applications to Drug Discovery Lead Discovery
4.17 Chemogenomics in Drug Discovery The Druggable Genome and Target Class Properties
4.18 Lead Discovery and the Concepts of Complexity and Lead Likeness in the Evolution of
Drug Candidates
4.19 Virtual Screening
4.20 Screening Library Selection and High Throughput Screening Analysis/Triage
Applications to Drug Discovery Ligand Based Lead Optimization
4.21 Pharmacophore Modeling: 2 Applications
4.22 Topological Quantitative Structure Activity Relationship Applications: Structure
Information Representation in Drug Discovery
4.23 Three Dimensional Quantitative Structure Activity Relationship: The State of the Art
Applications to Drug Discovery Target Structure Based
4.24 Structure Based Drug Design The Use of Protein Structure in Drug Discovery
4.25 Applications of Molecular Dynamics Simulations in Drug Design
4.26 Seven Transmembrane G Protein Coupled Receptors: Insights for Drug Design from
Structure and Modeling
4.27 Ion Channels: Insights for Drug Design from Structure and Modeling
4.28 Nuclear Hormone Receptors: Insights for Drug Design from Structure and Modeling
4.29 Enzymes: Insights for Drug Design from Structure
New Directions
4.30 Multiobjective/Multicriteria Optimization and Decision Support in Drug Discovery
4.31 New Applications for Structure Based Drug Design
4.32 Biological Fingerprints
Subject Index
Volume 5 ADME Tox Approaches
Introduction
5.01 The Why and How of Absorption, Distribution, Metabolism, Excretion, and Toxicity
Research
Biological and In Vivo Aspects of Absorption, Distribution, Metabolism, Excretion, and Toxicity
5.02 Clinical Pharmacokinetic Criteria for Drug Research
5.03 In Vivo Absorption, Distribution, Metabolism, and Excretion Studies in Discovery and
Development
5.04 The Biology and Function of Transporters
5.05 Principles of Drug Metabolism 1: Redox Reactions
Contents of all Volumes XV
5.06 Principles of Drug Metabolism 2: Hydrolysis and Conjugation Reactions
5.07 Principles of Drug Metabolism 3: Enzymes and Tissues
5.08 Mechanisms of Toxification and Detoxification which Challenge Drug Candidates and
Drugs
5.09 Immunotoxicology
Biological In Vitro Tools in Absorption, Distribution, Metabolism, Excretion, and Toxicity
5.10 In Vitro Studies of Drug Metabolism
5.11 Passive Permeability and Active Transport Models for the Prediction of Oral Absorption
5.12 Biological In Vitro Models for Absorption by Nonoral Routes
5.13 In Vitro Models for Examining and Predicting Brain Uptake of Drugs
5.14 In Vitro Models for Plasma Binding and Tissue Storage
5.15 Progress in Bioanalytics and Automation Robotics for Absorption, Distribution,
Metabolism, and Excretion Screening
Physicochemical tools in Absorption, Distribution, Metabolism, Excretion, and Toxicity
5.16 Ionization Constants and Ionization Profiles
5.17 Dissolution and Solubility
5.18 Lipophilicity, Polarity, and Hydrophobicity
5.19 Artificial Membrane Technologies to Assess Transfer and Permeation of Drugs in
Drug Discovery
5.20 Chemical Stability
5.21 Solid State Physicochemistry
In Silico Tools in Absorption, Distribution, Metabolism, Excretion, and Toxicity
5.22 Use of Molecular Descriptors for Absorption, Distribution, Metabolism, and Excretion
Predictions
5.23 Electrotopological State Indices to Assess Molecular and Absorption, Distribution, Metabolism,
Excretion, and Toxicity Properties
5.24 Molecular Fields to Assess Recognition Forces and Property Spaces
5.25 In Silico Prediction of Ionization
5.26 In Silico Predictions of Solubility
5.27 Rule Based Systems to Predict Lipophilicity
5.28 In Silico Models to Predict Oral Absorption
5.29 In Silico Prediction of Oral Bioavailability
5.30 In Silico Models to Predict Passage through the Skin and Other Barriers
5.31 In Silico Models to Predict Brain Uptake
5.32 In Silico Models for Interactions with Transporters
5.33 Comprehensive Expert Systems to Predict Drug Metabolism
5.34 Molecular Modeling and Quantitative Structure Activity Relationship of Substrates and
Inhibitors of Drug Metabolism Enzymes
5.35 Modeling and Simulation of Pharmacokinetic Aspects of Cytochrome P450 Based Metabolic
Drug Drug Interactions
5.36 In Silico Prediction of Plasma and Tissue Protein Binding
5.37 Physiologically Based Models to Predict Human Pharmacokinetic Parameters
5.38 Mechanism Based Pharmacokinetic Pharmacodynamic Modeling for the Prediction of
In Vivo Drug Concentration Effect Relationships Application in Drug Candidate
Selection and Lead Optimization
5.39 Computational Models to Predict Toxicity
5.40 In Silico Models to Predict QT Prolongation
5.41 The Adaptive In Combo Strategy
Enabling Absorption, Distribution, Metabolism, Excretion, and Toxicity Strategies and Technologies in
Early Development
5.42 The Biopharmaceutics Classification System
5.43 Metabonomics
Contents of all Volumes
5.44 Prodrug Objectives and Design
5.45 Drug Polymer Conjugates
List of Abbreviations
List of Symbols
Subject Index
Volume 6 Therapeutic Areas I: Central Nervous System, Pain, Metabolic Syndrome, Urology,
Gastrointestinal and Cardiovascular
Central Nervous System
6.01 Central Nervous System Drugs Overview
6.02 Schizophrenia
6.03 Affective Disorders: Depression and Bipolar Disorders
6.04 Anxiety
6.05 Attention Deficit Hyperactivity Disorder
6.06 Sleep
6.07 Addiction
6.08 Neurodegeneration
6.09 Neuromuscular/Autoimmune Disorders
6.10 Stroke/Traumatic Brain and Spinal Cord Injuries
6.11 Epilepsy
6.12 Ophthalmic Agents
Pain
6.13 Pain Overview
6.14 Acute and Neuropathic Pain
6.15 Local and Adjunct Anesthesia
6.16 Migraine
Obesity/Metabolic Disorders/Syndrome X
6.17 Obesity/Metabolic Syndrome Overview
6.18 Obesity/Disorders of Energy
6.19 Diabetes/Syndrome X
6.20 Atherosclerosis/Lipoprotein/Cholesterol Metabolism
6.21 Bone, Mineral, Connective Tissue Metabolism
6.22 Hormone Replacement
Urogenital
6.23 Urogenital Diseases/Disorders, Sexual Dysfunction and Reproductive
Medicine: Overview
6.24 Incontinence (Benign Prostatic Hyperplasia/Prostate Dysfunction)
6.25 Renal Dysfunction in Hypertension and Obesity
Gastrointestinal
6.26 Gastrointestinal Overview
6.27 Gastric and Mucosal Ulceration
6.28 Inflammatory Bowel Disease
6.29 Irritable Bowel Syndrome
6.30 Emesis Prokinetic Agents
Cardiovascular
6.31 Cardiovascular Overview
6.32 Hypertension
6.33 Antiarrhythmics
6.34 Thrombolytics
Subject Index
Contents of all Volumes xvii
Volume 7 Therapeutic Areas II: Cancer, Infectious Diseases, Inflammation Immunology and
Dermatology
And Cancer
7.01 Cancer Biology
7.02 Principles of Chemotherapy and Pharmacology
7.03 Antimetabolites
7.04 Microtubule Targeting Agents
7.05 Deoxyribonucleic Acid Topoisomerase Inhibitors
7.06 Alkylating and Platinum Antitumor Compounds
7.07 Endocrine Modulating Agents
7.08 Kinase Inhibitors for Cancer
7.09 Recent Development in Novel Anticancer Therapies
Anti Viral
7.10 Viruses and Viral Diseases
7.11 Deoxyribonucleic Acid Viruses: Antivirals for Herpesviruses and Hepatitis B Virus
7.12 Ribonucleic Acid Viruses: Antivirals for Human Immunodeficiency Virus
7.13 Ribonucleic Acid Viruses: Antivirals for Influenza A and B, Hepatitis C Virus, and
Respiratory Syncytial Virus
Anti Fungal
7.14 Fungi and Fungal Disease
7.15 Major Antifungal Drugs
Anti Bacterials
7.16 Bacteriology, Major Pathogens, and Diseases
7.17 (3 Lactam Antibiotics
7.18 Macrolide Antibiotics
7.19 Quinolone Antibacterial Agents
7.20 The Antibiotic and Nonantibiotic Tetracyclines
7.21 Aminoglycosides Antibiotics
7.22 Anti Gram Positive Agents of Natural Product Origins
7.23 Oxazolidinone Antibiotics
7.24 Antimycobacterium Agents
7.25 Impact of Genomics Emerging Targets for Antibacterial Therapy
Drugs for Parasitic Infections
7.26 Overview of Parasitic Infections
7.27 Advances in the Discovery of New Antimalarials
7.28 Antiprotozoal Agents (African Trypanosomiasis. Chagas Disease, and Leishmaniasis)
I and I Diseases
7.29 Recent Advances in Inflammatory and Immunologieal Diseases: Focus on Arthritis Therapy
7.30 Asthma and Chronic Obstructive Pulmonary Disease
7.31 Treatment of Transplantation Rejection and Multiple Sclerosis
Dermatology
7.32 Overview of Dermatological Diseases
7.33 Advances in the Discovery of Acne and Rosacea Treatments
7.34 New Treatments for Psoriasis and Atopic Dermatitis
Subject Index
Volume 8 Case Histories and Cumulative Subject Index
Personal Essays
8.01 Introduction
8.02 Reflections on Medicinal Chemistry Since the 1950s
Contents of all Volumes
8.03 Medicinal Chemistry as a Scientific Discipline in Industry and Academia: Some Personal
Reflections
8.04 Some Aspects of Medicinal Chemistry at the Schering Plough Research Institute
Case Histories
8.05 Viread
8.06 Hepsera
8.07 Ezetimibe
8.08 Tamoxifen
8.09 Raloxifene
8.10 Duloxetine
8.11 Carvedilol
8.12 Modafinil, A Unique Wake Promoting Drug: A Serendipitous Discovery in Search of a
Mechanism of Action
8.13 Zyvox
8.14 Copaxone
8.15 Ritonavir and Lopinavir/Ritonavir
8.16 Fosamax
8.17 Omeprazole
8.18 Calcium Channel oc2 5 Ligands: Gabapentin and Pregabalin
Cumulative Subject Index |
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| spelling | Comprehensive medicinal chemistry II 1 Global perspective ed.-in-chief: John B. Taylor... 1. ed. Amsterdam [u.a.] Elsevier 2007 1 Online-Ressource txt rdacontent c rdamedia cr rdacarrier Taylor, John B. Sonstige oth (DE-604)BV022938881 1 http://www.sciencedirect.com/science/referenceworks/9780080450445 Verlag Volltext HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016143587&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Comprehensive medicinal chemistry II |
| title | Comprehensive medicinal chemistry II |
| title_auth | Comprehensive medicinal chemistry II |
| title_exact_search | Comprehensive medicinal chemistry II |
| title_exact_search_txtP | Comprehensive medicinal chemistry II |
| title_full | Comprehensive medicinal chemistry II 1 Global perspective ed.-in-chief: John B. Taylor... |
| title_fullStr | Comprehensive medicinal chemistry II 1 Global perspective ed.-in-chief: John B. Taylor... |
| title_full_unstemmed | Comprehensive medicinal chemistry II 1 Global perspective ed.-in-chief: John B. Taylor... |
| title_short | Comprehensive medicinal chemistry II |
| title_sort | comprehensive medicinal chemistry ii global perspective |
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