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Methods and Principles in Medicinal Chemistry: Reactive Drug Metabolites - Kalgutkar, Amit S. / Dalvie, Deepak / Obach, R. Scott
Vergriffenes Buch, derzeit bei uns nicht verfügbar.
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Kalgutkar, Amit S. / Dalvie, Deepak / Obach, R. Scott:
Methods and Principles in Medicinal Chemistry: Reactive Drug Metabolites - gebunden oder broschiert

2012, ISBN: 9783527330850

[ED: Buch, gebundene Ausgabe], [PU: Wiley-VCH], KURZE BESCHREIBUNG/ANMERKUNGEN: This first comprehensive introduction to the topic discusses the current best practice to manage toxicity risks in new drugs, including an in-depth analysis of the toxicological potential of the top 200 prescription drugs. AUSFÜHRLICHERE BESCHREIBUNG: Closing a gap in the scientifi c literature, this first comprehensive introduction to the topic is based on current best practice in one of the largest pharmaceutical companies worldwide. The first chapters trace the development of our understanding of drug metabolite toxicity, covering basic concepts and techniques in the process, while the second part details chemical toxicophores that are prone to reactive metabolite formation. This section also reviews the various drug-metabolizing enzymes that can participate in catalyzing reactive metabolite formation, including a discussion of the structure-toxicity relationships for drugs. Two chapters are dedicated to the currently hot topics of herbal constituents and IADRs. The next part covers current strategies and approaches to evaluate the reactive metabolite potential of new drug candidates, both by predictive and by bioanalytical methods. There then follows an in-depth analysis of the toxicological potential of the top 200 prescription drugs, illustrating the power and the limits of the toxicophore concept, backed by numerous case studies. Finally, a risk-benefi t approach to managing the toxicity risk of reactive metabolite-prone drugs is presented. Since the authors carefully develop the knowledge needed, from fundamental considerations to current industry standards, no degree in pharmacology is required to read this book, making it perfect for medicinal chemists without in-depth pharmacology training. INHALT: Preface XIII A Personal Foreword XV 1 Origin and Historical Perspective on Reactive Metabolites 1 Abbreviations 1 1.1 Mutagenesis and Carcinogenesis 1 1.2 Detection of Reactive Metabolites 3 1.3 Induction and Inhibition: Early Probes for Reactive Metabolites and Hepatotoxicants 4 1.4 Covalent Binding and Oxidative Stress: Possible Mechanisms of Reactive Metabolite Cytotoxicity 5 1.5 Activation and Deactivation: Intoxication and Detoxification 6 1.6 Genetic Influences on Reactive Metabolite Formation 6 1.7 Halothane: the Role of Reactive Metabolites in Immune-Mediated Toxicity 7 1.8 Formation of Reactive Metabolites, Amount Formed, and Removal of Liability 8 1.9 Antibodies: Possible Clues but Inconclusive 8 1.10 Parent Drug and Not Reactive Metabolites, Complications in Immune-Mediated Toxicity 9 1.11 Reversible Pharmacology Should not be Ignored as a Primary Cause of Side Effects 10 1.12 Conclusions: Key Points in the Introduction 10 References 11 2 Role of Reactive Metabolites in Genotoxicity 13 Abbreviations 13 2.1 Introduction 13 2.2 Carcinogenicity of Aromatic and Heteroaromatic Amines 13 2.3 Carcinogenicity of Nitrosamines 17 2.4 Carcinogenicity of Quinones and Related Compounds 19 2.5 Carcinogenicity of Furan 23 2.6 Carcinogenicity of Vinyl Halides 26 2.7 Carcinogenicity of Ethyl Carbamate 26 2.8 Carcinogenicity of Dihaloalkanes 28 2.9 Assays to Detect Metabolism-Dependent Genotoxicity in Drug Discovery 28 2.10 Case Studies in Eliminating Metabolism-Based Mutagenicity in Drug Discovery Programs 29 References 36 3 Bioactivation and Inactivation of Cytochrome P450 and Other Drug-Metabolizing Enzymes 43 Abbreviations 43 3.1 Introduction 43 3.2 Pharmacokinetic and Enzyme Kinetic Principles Underlying Mechanism-Based Inactivation and Drug-Drug Interactions 44 3.2.1 Enzyme Kinetic Principles of Mechanism-Based Inactivation 44 3.2.2 Pharmacokinetic Principles Underlying DDIs Caused by Mechanism-Based Inactivation 46 3.3 Mechanisms of Inactivation of Cytochrome P450 Enzymes 47 3.3.1 Quasi-Irreversible Inactivation 47 3.3.2 Heme Adducts 48 3.3.3 Protein Adducts 49 3.4 Examples of Drugs and Other Compounds that are Mechanism-Based Inactivators of Cytochrome P450 Enzymes 49 3.4.1 Amines 49 3.4.2 Methylenedioxyphenyl Compounds 51 3.4.3 Quinones, Quinone Imines, and Quinone Methides 52 3.4.4 Thiophenes 53 3.4.5 Furans 55 3.4.6 Alkynes 56 3.4.7 2-Alkylimidazoles 57 3.4.8 Other Noteworthy Cytochrome P450 Inactivators 58 3.5 Mechanism-Based Inactivation of Other Drug-Metabolizing Enzymes 60 3.5.1 Aldehyde Oxidase 60 3.5.2 Monoamine Oxidases 61 3.6 Concluding Remarks 64 References 65 4 Role of Reactive Metabolites in Drug-Induced Toxicity - The Tale of Acetaminophen, Halothane, Hydralazine, and Tienilic Acid 71 Abbreviations 71 4.1 Introduction 71 4.2 Acetaminophen 71 4.2.1 Metabolism of Acetaminophen 72 4.2.2 Metabolic Activation of Acetaminophen 73 4.3 Halothane 75 4.3.1 Metabolism of Halothane 76 4.3.2 Hepatotoxicity following Halothane Administration 78 4.4 Hydralazine 79 4.5 Tienilic Acid 82 References 84 5 Pathways of Reactive Metabolite Formation with Toxicophores/-Structural Alerts 93 Abbreviations 93 5.1 Introduction 93 5.2 Intrinsically Reactive Toxicophores 93 5.2.1 Electrophilic Functional Groups 94 5.2.2 Metal Complexing Functional Groups 96 5.3 Toxicophores that Require Bioactivation to Reactive Metabolites 98 5.3.1 Aromatic Amines (Anilines) 98 5.3.2 ortho- and para-Aminophenols 101 5.3.3 Nitroarenes 103 5.3.4 Hydrazines 105 5.3.5 Five-Membered Heteroaromatic Rings 107 5.3.5.1 Furans 107 5.3.5.2 Thiophenes 109 5.3.5.3 Thiazoles and 2-Aminothiazoles 109 5.3.5.4 3-Alkyl Pyrrole and 3-Alkylindole Derivatives 112 5.3.5.5 1,3-Benzdioxole (Methylenedioxyphenyl) Motif 115 5.3.6 Termina, DE, [SC: 0.00], Neuware, gewerbliches Angebot, H: 240mm, B: 170mm, 386, [GW: 1012g], Selbstabholung und Barzahlung, PayPal, offene Rechnung, Banküberweisung, Interntationaler Versand

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Reactive Drug Metabolites, Volume 55 - Amit S. Kalgutkar, Deepak Dalvie, R. Scott Obach, Dennis A. Smith, Raimund Mannhold, Hugo Kubinyi, Gerd Folkers
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Amit S. Kalgutkar, Deepak Dalvie, R. Scott Obach, Dennis A. Smith, Raimund Mannhold, Hugo Kubinyi, Gerd Folkers:
Reactive Drug Metabolites, Volume 55 - gebunden oder broschiert

ISBN: 3527330852

[SR: 1752900], Hardcover, [EAN: 9783527330850], Wiley-VCH, Wiley-VCH, Book, [PU: Wiley-VCH], Wiley-VCH, Closing a gap in the scientifi c literature, this first comprehensive introduction to the topic is based on current best practice in one of the largest pharmaceutical companies worldwide. The first chapters trace the development of our understanding of drug metabolite toxicity, covering basic concepts and techniques in the process, while the second part details chemical toxicophores that are prone to reactive metabolite formation. This section also reviews the various drug-metabolizing enzymes that can participate in catalyzing reactive metabolite formation, including a discussion of the structure-toxicity relationships for drugs. Two chapters are dedicated to the currently hot topics of herbal constituents and IADRs. The next part covers current strategies and approaches to evaluate the reactive metabolite potential of new drug candidates, both by predictive and by bioanalytical methods. There then follows an in-depth analysis of the toxicological potential of the top 200 prescription drugs, illustrating the power and the limits of the toxicophore concept, backed by numerous case studies. Finally, a risk-benefi t approach to managing the toxicity risk of reactive metabolite-prone drugs is presented. Since the authors carefully develop the knowledge needed, from fundamental considerations to current industry standards, no degree in pharmacology is required to read this book, making it perfect for medicinal chemists without in-depth pharmacology training., 13575, Clinical, 13570, Chemistry, 75, Science & Math, 1000, Subjects, 283155, Books, 265544, Pharmacology, 16311581, Cardiovascular, 16311631, Chemistry, 16311601, Clinical, 16311591, Drug Delivery Systems, 227673, Drug Guides, 227661, For Nurses, 227738, For Veterinarians, 16311541, Molecular, 16311571, Neuropsychopharmacology, 265547, Pain Medicine, 16311561, Pharmacodynamics, 265548, Pharmacy, 16311611, Product Development, 16311551, Reference, 265549, Toxicology, 173514, Medical Books, 1000, Subjects, 283155, Books, 689721011, Pharmacology, 689709011, Basic Sciences, 689674011, Medicine, 468228, Medicine & Health Sciences, 465600, New, Used & Rental Textbooks, 2349030011, Specialty Boutique, 283155, Books

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This first comprehensive introduction to the topic discusses the current best practice to manage toxicity risks in new drugs, including an in-depth analysis of the toxicological potential of the top 200 prescription drugs. Closing a gap in the scientifi c literature, this first comprehensive introduction to the topic is based on current best practice in one of the largest pharmaceutical companies worldwide. The first chapters trace the development of our understanding of drug metabolite toxicity, covering basic concepts and techniques in the process, while the second part details chemical toxicophores that are prone to reactive metabolite formation. This section also reviews the various drug-metabolizing enzymes that can participate in catalyzing reactive metabolite formation, including a discussion of the structure-toxicity relationships for drugs. Two chapters are dedicated to the currently hot topics of herbal constituents and IADRs. The next part covers current strategies and approaches to evaluate the reactive metabolite potential of new drug candidates, both by predictive and by bioanalytical methods. There then follows an in-depth analysis of the toxicological potential of the top 200 prescription drugs, illustrating the power and the limits of the toxicophore concept, backed by numerous case studies. Finally, a risk-benefi t approach to managing the toxicity risk of reactive metabolite-prone drugs is presented. Since the authors carefully develop the knowledge needed, from fundamental considerations to current industry standards, no degree in pharmacology is required to read this book, making it perfect for medicinal chemists without in-depth pharmacology training. Bücher / Fremdsprachige Bücher / Englische Bücher 978-3-527-33085-0, Wiley-VCH

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Smith, Dennis A.;Mannhold, Raimund;Kalgutkar, Amit S.;Dalvie, Deepak;Obach, R. Scott: Reactive Drug Metabolites
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Methods and Principles in Medicinal Chemistry. 1. Auflage Methods and Principles in Medicinal Chemistry. 1. Auflage Bücher > English, International > Gebundene Ausgaben, [PU: Wiley-VCH, Weinheim]

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Details zum Buch
Reactive Drug Metabolites
Autor:

Kalgutkar, Amit S. / Dalvie, Deepak / Obach, R. Scott / Smith, Dennis

Titel:

Reactive Drug Metabolites

ISBN-Nummer:

Closing a gap in the scientifi c literature, this first comprehensive introduction to the topic is based on current best practice in one of the largest
pharmaceutical companies worldwide. The first chapters trace the development of our understanding of drug metabolite toxicity, covering basic concepts and techniques in the process, while the second part details chemical toxicophores that are prone to reactive metabolite formation. This section also reviews the various drug-metabolizing enzymes that can participate in catalyzing reactive metabolite formation, including a discussion of the structure-toxicity relationships for drugs. Two chapters are dedicated to the currently hot topics of herbal constituents and IADRs.

The next part covers current strategies and approaches to evaluate the reactive metabolite potential of new drug candidates, both by predictive
and by bioanalytical methods. There then follows an in-depth analysis of the toxicological potential of the top 200 prescription drugs, illustrating
the power and the limits of the toxicophore concept, backed by numerous case studies. Finally, a risk-benefi t approach to managing the toxicity risk of reactive metabolite-prone drugs is presented.

Since the authors carefully develop the knowledge needed, from fundamental considerations to current industry standards, no degree in pharmacology is required to read this book, making it perfect for medicinal chemists without in-depth pharmacology training.

Detailangaben zum Buch - Reactive Drug Metabolites


EAN (ISBN-13): 9783527330850
ISBN (ISBN-10): 3527330852
Gebundene Ausgabe
Erscheinungsjahr: 2012
Herausgeber: Wiley VCH Verlag GmbH
386 Seiten
Gewicht: 1,017 kg
Sprache: Englisch

Buch in der Datenbank seit 28.04.2007 00:39:27
Buch zuletzt gefunden am 16.07.2017 21:29:06
ISBN/EAN: 3527330852

ISBN - alternative Schreibweisen:
3-527-33085-2, 978-3-527-33085-0


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