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2011, ISBN: 9783527326037

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2011, ISBN: 3527326030

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Prodrugs and Targeted Delivery - Erstausgabe

2010, ISBN: 9783527326037

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Towards Better ADME Properties, Buch, Hardcover, 1. Auflage, [PU: Wiley-VCH], Wiley-VCH, 2010

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Details zum Buch
Prodrugs and Targeted Delivery

This topical reference and handbook addresses the chemistry, pharmacology, toxicology and the patentability of prodrugs, perfectly mirroring the integrated approach prevalent in today's drug design. It summarizes current experiences and strategies for the rational design of prodrugs, beginning at the early stages of the development process, as well as discussing organ- and site-selective prodrugs. Every company employing medicinal chemists will be interested in this practice-oriented overview of a key strategy in modern drug discovery and development.

Detailangaben zum Buch - Prodrugs and Targeted Delivery

EAN (ISBN-13): 9783527326037
ISBN (ISBN-10): 3527326030
Gebundene Ausgabe
Erscheinungsjahr: 2010
Herausgeber: Wiley-VCH
496 Seiten
Gewicht: 1,104 kg
Sprache: eng/Englisch

Buch in der Datenbank seit 2007-01-16T12:28:29+01:00 (Vienna)
Detailseite zuletzt geändert am 2022-02-17T17:57:38+01:00 (Vienna)
ISBN/EAN: 9783527326037

ISBN - alternative Schreibweisen:
3-527-32603-0, 978-3-527-32603-7

Daten vom Verlag:

Autor/in: Jarkko Rautio
Titel: Methods and Principles in Medicinal Chemistry; Prodrugs and Targeted Delivery - Towards Better ADME Properties
Verlag: Wiley-VCH; Wiley-VCH
496 Seiten
Erscheinungsjahr: 2010-12-15
Gedruckt / Hergestellt in Deutschland.
Gewicht: 1,432 kg
Sprache: Englisch
185,00 € (DE)
190,20 € (AT)
170mm x 240mm x 39mm

BB; Hardcover, Softcover / Chemie; Medizinische Chemie, Pharmazeutische Chemie; Verstehen; Medizin, Gesundheit; Arzneimittelentwicklung; Arzneimittelforschung; Chemie; Chemistry; Drug Discovery & Development; Drug Formulation & Delivery; Toxicology; Toxikologie; Wirkstoff; Wirkstoffformulierung, Wirkstofftransport; Wirkstoffforschung u. -entwicklung; Wirkstoffforschung u. -entwicklung; Wirkstoffformulierung, Wirkstofftransport; Toxikologie

Preface PART ONE: Prodrug Design and Intellectual Property PRODRUG STRATEGIES IN DRUG DESIGN Prodrug Concept Basics of Prodrug Design Rationale for Prodrug Design History of Prodrug Design Recently Marketed Prodrugs Concluding Remarks THE MOLECULAR DESIGN OF PRODRUGS BY FUNCTIONAL GROUP Introduction The Prodrug Concept and Basics of Design Common Functional Group Approaches in Prodrug Design Conclusions INTELLECTUAL PROPERTY PRIMER ON PHRAMACEUTICAL PATENTS WITH A SPECIAL EMPHASIS ON PRODRUGS AND METABOLITES Introduction Patents and FDA Approval Process Obtaining a Patent Conclusion PART TWO: Prodrugs Addressing ADMET Issues INCREADING LIPOPHILICITY FOR ORAL DRUG DELIVERY Introduction pKa, Degree of Ionization, Partition Coefficient, and Distribution Coefficient Prodrug Strategies to Enhance Lipid Solubility Prodrug Examples for Antibiotics Antiviral Related Prodrugs Cardiovascular Related Prodrugs Lipophilic Prodrugs of Benzamidine Drugs Miscellaneous Examples Summary and Conclusion MODULATING SOLUBILITY THROUGH PRODRUGS FOR ORAL AND IV DRUG DELIVERY Introduction Basics of Solubility and Oral/IV Drug Delivery Prodrug Applications for Enhanced Aqueous Solubility Challenges with Solubilizing Prodrugs of Insoluble Drugs Additional Applications of Prodrugs for Modulating Solubility Parallel Exploration of Analogues and Prodrugs in Drug Discovery (Commentary) Conclusions PRODRUGS DESIGNED TO TARGET TRANSPORTERS FOR ORAL DRUG DELIVERY Introduction Serendipity: An Actively Transported Prodrug Requirements for Actively Transported Prodrugs Peptide Transporters: PEPT1 and PEPT2 Monocarboxylate Transporters Bile Acid Transporters Conclusions TOPICAL AND TRANSDERMAL DELIVERY USING PRODRUGS: MECHANISM OF ENHANCEMENT Introduction Arrangement of Water in the Stratum Corneum A New Model for Diffusion Through the Stratum Corneum: The Biphasic Solubility Model Equations for Quantifying Effects of Solubility on Diffusion Through the Stratum Corneum Design of Prodrugs for Topical and Transdermal Delivery Based on the Biphasic Solubility Model Comparison of Human and Mouse Skin Experiments Summary OCULAR DELIVERY USING PRODRUGS Introduction Criteria for an Ideal Ophthalmic Prodrug Anatomy and Physiology of the Eye Barriers to Ocular Drug Delivery Influx and Efflux Transporters on the Eye Transporter-Targeted Prodrug Approach Drug Disposition in Ocular Delivery Effect of Physiochemical Factors on Drug Disposition in Eye Prodrug Strategy to Improve Ocular Bioavailability (Nontransporter-Targeted Approach) Recent Patents and Marketed Ocular Prodrugs Novel Formulation Approaches for Sustained Delivery of Prodrugs Conclusion REDUCING PRESYSTEMIC DRUG METABOLISM Introduction Presystemic Metabolic Barriers Prodrug Approaches to Reduce Presystemic Drug Metabolism Targeting Colon Targeting Lymphatic Route Conclusion ENZYME-ACTIVATED PRODRUG STRATEGIES FOR SITE-SELECTIVE DRUG DELIVERY Introduction General Requirements for Enzyme-Activated Targeted Prodrug Strategy Examples of Targeted Prodrug Strategies Summary PRODRUG APPROACHES FOR CENTRAL NERVOUS SYSTEM DELIVERY Blood-Brain Barrier in CNS Drug Development Prodrug Strategies Prodrug Strategies Based Upon BBB Nutrient Transporters Prodrug Strategies Based Upon BBB Receptors CNS Prodrug Summary DIRECTED ENZYME PRODRUG THERAPIES Introduction Theoretical Background of DEPT Comparison of ADEPT and GDEPT Enzymes in ADEPT and GDEPT Design of Prodrugs Strategies Used for the Improvement of DEPT Systems Biological Data for ADEPT and GDEPT Conclusions PART THREE: Codrugs and Soft Drugs IMPROVING THE USE OF DRUG COMBINATIONS THROUGH THE CODRUG APPROACH Codrugs and Codrug Strategy Ideal Codrug Characteristics Examples of Marketed Codrugs Topical Codrug Therapy for the Treatment of Ophthalmic Diseases Codrugs for Transdermal Delivery Codrugs of L-DOPA for the Treatment of Parkinson's Disease Analgesic Codrugs Containing Nonsteroidal Anti-Inflammatory Agents Analgesic Codrugs of Opioids and Cannabinoids Codrugs Containing Anti-HIV Drugs SOFT DRUGS Introduction Indications Design Considerations Case Study: The Discovery of Esmolol Summary PART FOUR: Preclinical and Clinical Considerations for Prodrugs PHARMACOKINETIC AND BIOPHARMACEUTICAL CONSIDERATIONS IN PRODRUG DISCOVERY AND DEVELOPMENT Introduction Understanding Pharmacokinetic/Pharmacodynamic Relationships Pharmacokinetics Tools for the Prodrug Scientist Enzymes Involved with Prodrug Conversion Use of the Caco-2 System for Permeability and Active Transport Evaluation XP13512: Improving PK Performance by Targeting Active Transport Prodrug Absorption: Transport/Metabolic Conversion Interplay Preabsorptive Degradation Biopharmaceutical-Based PK Modeling for Prodrug Design Conclusions THE IMPACT OF PHARMACOGENETICS ON THE CLINICAL OUTCOMES OF PRODRUGS Introduction Clopidogrel and CYP2C19 Codeine and CYP2D6 Tamoxifen and CYP2D6 Fluorouracil Prodrugs and Carboxylesterase Irinotecan and Carboxylesterase 2 Others Drug Development Implication Conclusions

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