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Methods and Principles in Medicinal Chemistry: Reactive Drug Metabolites
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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 largestpharmaceutical 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 predictiveand by bioanalytical methods. There then follows an in-depth analysis of the toxicological potential of the top 200 prescription drugs, illustratingthe 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 XIIIA Personal Foreword XV1 Origin and Historical Perspective on Reactive Metabolites 1Abbreviations 11.1 Mutagenesis and Carcinogenesis 11.2 Detection of Reactive Metabolites 31.3 Induction and Inhibition: Early Probes for Reactive Metabolites and Hepatotoxicants 41.4 Covalent Binding and Oxidative Stress: Possible Mechanisms of Reactive Metabolite Cytotoxicity 51.5 Activation and Deactivation: Intoxication and Detoxification 61.6 Genetic Influences on Reactive Metabolite Formation 61.7 Halothane: the Role of Reactive Metabolites in Immune-Mediated Toxicity 71.8 Formation of Reactive Metabolites, Amount Formed, and Removal of Liability 81.9 Antibodies: Possible Clues but Inconclusive 81.10 Parent Drug and Not Reactive Metabolites, Complications in Immune-Mediated Toxicity 91.11 Reversible Pharmacology Should not be Ignored as a Primary Cause of Side Effects 101.12 Conclusions: Key Points in the Introduction 10References 112 Role of Reactive Metabolites in Genotoxicity 13Abbreviations 132.1 Introduction 132.2 Carcinogenicity of Aromatic and Heteroaromatic Amines 132.3 Carcinogenicity of Nitrosamines 172.4 Carcinogenicity of Quinones and Related Compounds 192.5 Carcinogenicity of Furan 232.6 Carcinogenicity of Vinyl Halides 262.7 Carcinogenicity of Ethyl Carbamate 262.8 Carcinogenicity of Dihaloalkanes 282.9 Assays to Detect Metabolism-Dependent Genotoxicity in Drug Discovery 282.10 Case Studies in Eliminating Metabolism-Based Mutagenicity in Drug Discovery Programs 29References 363 Bioactivation and Inactivation of Cytochrome P450 and Other Drug-Metabolizing Enzymes 43Abbreviations 433.1 Introduction 433.2 Pharmacokinetic and Enzyme Kinetic Principles Underlying Mechanism-Based Inactivation and Drug-Drug Interactions 443.2.1 Enzyme Kinetic Principles of Mechanism-Based Inactivation 443.2.2 Pharmacokinetic Principles Underlying DDIs Caused by Mechanism-Based Inactivation 463.3 Mechanisms of Inactivation of Cytochrome P450 Enzymes 473.3.1 Quasi-Irreversible Inactivation 473.3.2 Heme Adducts 483.3.3 Protein Adducts 493.4 Examples of Drugs and Other Compounds that are Mechanism-Based Inactivators of Cytochrome P450 Enzymes 493.4.1 Amines 493.4.2 Methylenedioxyphenyl Compounds 513.4.3 Quinones, Quinone Imines, and Quinone Methides 523.4.4 Thiophenes 533.4.5 Furans 553.4.6 Alkynes 563.4.7 2-Alkylimidazoles 573.4.8 Other Noteworthy Cytochrome P450 Inactivators 583.5 Mechanism-Based Inactivation of Other Drug-Metabolizing Enzymes 603.5.1 Aldehyde Oxidase 603.5.2 Monoamine Oxidases 613.6 Concluding Remarks 64References 654 Role of Reactive Metabolites in Drug-Induced Toxicity - The Tale of Acetaminophen, Halothane, Hydralazine, and Tienilic Acid 71Abbreviations 714.1 Introduction 714.2 Acetaminophen 714.2.1 Metabolism of Acetaminophen 724.2.2 Metabolic Activation of Acetaminophen 734.3 Halothane 754.3.1 Metabolism of Halothane 764.3.2 Hepatotoxicity following Halothane Administration 784.4 Hydralazine 794.5 Tienilic Acid 82References 845 Pathways of Reactive Metabolite Formation with Toxicophores/-Structural Alerts 93Abbreviations 935.1 Introduction 935.2 Intrinsically Reactive Toxicophores 935.2.1 Electrophilic Functional Groups 945.2.2 Metal Complexing Functional Groups 965.3 Toxicophores that Require Bioactivation to Reactive Metabolites 985.3.1 Aromatic Amines (Anilines) 985.3.2 ortho- and para-Aminophenols 1015.3.3 Nitroarenes 1035.3.4 Hydrazines 1055.3.5 Five-Membered Heteroaromatic Rings 1075.3.5.1 Furans 1075.3.5.2 Thiophenes 1095.3.5.3 Thiazoles and 2-Aminothiazoles 1095.3.5.4 3-Alkyl Pyrrole and 3-Alkylindole Derivatives 1125.3.5.5 1,3-Benzdioxole (Methylenedioxyphenyl) Motif 1155.3.6 Termina, [SC: 0.00]

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Reactive Drug Metabolites, Volume 55 - Hugo Kubinyi, Deepak Dalvie, R. Scott Obach
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Hugo Kubinyi, Deepak Dalvie, R. Scott Obach:

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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. Hugo Kubinyi, Deepak Dalvie, R. Scott Obach, Books, Health and Well Being, Reactive Drug Metabolites, Volume 55 Books>Health and Well Being, Wiley

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Reactive Drug Metabolites - Amit S. Kalgutkar
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Reactive Drug Metabolites - neues Buch

ISBN: 9783527330850

[ED: Buch], [PU: Wiley VCH Verlag GmbH], Neuware - 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., [SC: 0.00], Neuware, gewerbliches Angebot, 250x178x10 mm, [GW: 1017g]

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Reactive Drug Metabolites (Methods and Principles in Medicinal Chemistry, Band 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:
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[SR: 929082], Gebundene Ausgabe, [EAN: 9783527330850], Wiley-VCH Verlag GmbH & Co. KGaA, Wiley-VCH Verlag GmbH & Co. KGaA, Book, [PU: Wiley-VCH Verlag GmbH & Co. KGaA], Wiley-VCH Verlag GmbH & Co. KGaA, 56048011, Chemie, 56049011, Analytische Chemie, 56053011, Anorganische Chemie, 56087011, Biochemie, 56090011, Chemische Physik, 56077011, Chromatografie, 56086011, Fotochemie, 56088011, Geochemie, 56070011, Industrie & Technik, 56082011, Katalyse, 1320289031, Klinische Chemie, 56051011, Kristallografie, 56083011, Molekularchemie, 56071011, Oberflächenchemie, 56054011, Organische Chemie, 56062011, Physisch & Theoretisch, 56079011, Polymere & Makromoleküle, 56072011, Sicherheit, 56047011, Fachbücher, 54071011, Genres, 52044011, Fremdsprachige Bücher, 56687011, Pharmakologie, 56690011, Pharmazie, 56689011, Schmerzmittel, 56691011, Toxikologie, 56535011, Medizin, 54071011, Genres, 52044011, Fremdsprachige Bücher

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Reactive Drug Metabolites - Hugo Kubinyi
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Reactive Drug Metabolites - gebunden oder broschiert

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Hardback, [PU: Wiley-VCH Verlag GmbH], 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., Pharmacology

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Reactive Drug Metabolites
Autor:

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

Titel:

Reactive Drug Metabolites

ISBN-Nummer:

9783527330850

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 07.12.2016 00:42:14
ISBN/EAN: 9783527330850

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

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