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Drug-Like Properties : Concepts, Structure Design and Methods from ADME to Toxicity Optimization /
Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, only a fraction have sufficient ADME (absorption, distribution, metabolism, elimination) properties, and acceptable toxicology properties, to become a drug product that will succes...
| Clasificación: | Libro Electrónico |
|---|---|
| Autores principales: | , |
| Formato: | Electrónico eBook |
| Idioma: | Inglés |
| Publicado: |
Academic Press,
2016.
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| Edición: | 2nd. |
| Temas: | |
| Acceso en línea: | Texto completo |
Tabla de Contenidos:
- Front Cover; Drug-Like Properties: Concepts, Structure, Design, and Methods from ADME to Toxicity Optimization; Copyright; Dedication; Contents; Preface; Preface to Second Edition; Preface to First Edition; Chapter 1: Introduction; 1.1. Drug-like Properties in Drug Discovery; 1.2. Purpose of This Book; Problems; References; Chapter 2: Benefits of Property Assessment and Good Drug-Like Properties; 2.1. Introduction; 2.2. Discovery Scientists Optimize Many Properties; 2.3. Introduction to the Drug Discovery and Development Process; 2.4. Benefits of Good Drug-like Properties.
- 2.4.1. Reduced Development Attrition2.4.2. More Efficient Drug Discovery; 2.4.3. More Efficient Drug Development; 2.4.4. Higher Patient Compliance; 2.4.5. Improved Biological Research in Drug Discovery; 2.4.6. Enabled Partnerships for Drug Development; 2.4.7. Human Modeling and Clinical Planning; 2.4.8. Balance of Properties and Activity; 2.5. Property Profiling in Drug Discovery; 2.6. Drug-like Property Optimization in Drug Discovery; Problems; References; Chapter 3: In Vivo Environments Affect Drug Exposure; 3.1. Introduction; 3.2. Drug Dosing; 3.3. Stomach.
- 3.3.1. Gastric Acidic Degradation3.4. Intestinal Environment; 3.4.1. Dissolution Rate; 3.4.2. Solubility; 3.4.3. Permeability; 3.4.4. Intestinal Metabolism; 3.4.5. Intestinal Enzymatic Hydrolysis; 3.4.6. Absorption Enhancement in the Intestine; 3.5. Bloodstream; 3.5.1. Plasma Enzyme Hydrolysis; 3.5.2. Plasma Protein Binding; 3.5.3. Red Blood Cell Binding; 3.6. Liver; 3.6.1. Permeation into and out of Hepatocytes; 3.6.2. Hepatic Metabolism; 3.6.3. Biliary Extraction; 3.7. Kidney; 3.8. Blood-Tissue Barriers; 3.9. Tissue Distribution; 3.9.1. Nonspecific Binding in Tissue.
- 3.10. Consequences of Chirality3.11. Overview of in vivo Challenges to Drug Exposure; Problems; References; Chapter 4: Prediction Rules for Rapid Property Profiling from Structure; 4.1. Introduction; 4.2. General Concepts for Prediction Rules; 4.3. Rule of 5; 4.4. Veber Rules; 4.5. Waring Rules; 4.6. Golden Triangle; 4.7. Other Predictive Rules; 4.8. Application of Rules for Compound Assessment; 4.9. Applications of Predictive Rules; Problems; References; Chapter 5: Lipophilicity; 5.1. Lipophilicity Fundamentals; 5.2. Lipophilicity Effects.
- 5.3. Lipophilicity Case Studies and Structure Modification5.3.1. Lipophilicity Modification for Biological Activity; 5.3.2. Lipophilicity Modification for Pharmacokinetics; 5.3.3. Lipophilicity Modification for Toxicity; Problems; References; Chapter 6: pKa; 6.1. pKa Fundamentals; 6.2. pKa Effects; 6.2.1. pKa Affects Efficacy; 6.2.2. pKa Affects Pharmacokinetics; 6.2.3. pKa Affects Toxicity; 6.3. pKa Case Studies; 6.3.1. pKa and Activity Examples; 6.3.2. pKa and Pharmacokinetics Examples; 6.4. Structure Modification Strategies for pKa; Problems; References; Chapter 7: Solubility.