The medicinal chemist's guide to solving ADMET challenges / edited by Patrick Schnider.

Includes index.

Print version record.

Intro -- Half Title -- Drug Discovery Series -- Title -- Copyright -- Preface -- Contents -- Chapter 1 Overview of Strategies for Solving ADMET Challenges -- 1.1 Introduction -- 1.2 Strategies by ADMET Properties -- 1.2.1 Tactics to Improve Solubility (Chapter 2) -- 1.2.2 Optimisation of Passive Permeability for Oral Absorption (Chapter 3) -- 1.2.3 Targeting Gastrointestinal Uptake Transporters (Chapter 4) -- 1.2.4 Drug Efflux Transporters: P-gp and BCRP (Chapter 5) -- 1.2.5 OATs and OCTs: The SLC22 Family of Organic Anion and Cation Transporters (Chapter 6)

1.2.6 OATPs: The SLCO Family of Organic Anion Transporting Polypeptide Transporters (Chapter 7) -- 1.2.7 Bile Salt Export Pump (BSEP) Inhibition (Chapter 8) -- 1.2.8 Cytochrome P450 Metabolism (Chapter 9) -- 1.2.9 Cytochrome P450 Induction (Chapter 10) -- 1.2.10 Strategies to Mitigate CYP450 Inhibition (Chapter 11) -- 1.2.11 Aldehyde and Xanthine Oxidase Metabolism (Chapter 12) -- 1.2.12 Glucuronidation (Chapter 13) -- 1.2.13 Sulfation (Chapter 14) -- 1.2.14 Reactive Metabolites (Chapter 15) -- 1.2.15 Genotoxicity (Chapter 16) -- 1.2.16 Drug-induced Photosensitivity (Chapter 17)

1.2.17 Drug-induced Phospholipidosis (Chapter 18) -- 1.2.18 Cardiac Ion Channel Inhibition (Chapter 19) -- 1.3 Strategies by Molecular Properties -- References -- Chapter 2 Tactics to Improve Solubility -- 2.1 Introduction: Relevance of Solubility for Drug Disposition -- 2.2 Definitions -- 2.2.1 Which Solubility Measure is Most Pertinent? -- 2.2.2 Solubility, Lipophilicity and pKa -- 2.2.3 General Solubility Equation (GSE) -- 2.2.4 Other Predictors: In Silico -- 2.3 Mitigation Strategies -- 2.3.1 Decrease Lipophilicity -- 2.3.2 Charge -- 2.3.3 Introduction of Polar Substituents

2.3.4 Replacement of Aromatic CH by N or O -- 2.3.5 Reduce Crystal Packing and Melting Point -- 2.3.6 Salt Forms -- 2.4 Examples of Mitigation Strategies -- 2.4.1 Changing Lipophilicity, Adding Polar Groups, Twists -- 2.4.2 Solid State Structure Manipulation to Reduce Melting Point -- 2.4.3 Modulating Intramolecular Interactions -- Reducing Melting Point -- 2.4.4 Reducing Planarity -- 2.4.5 Heterocyclic Switches, Reducing Aromaticity -- 2.4.6 Heterocyclic Switch -- 2.4.7 Disruption of Planarity -- 2.4.8 Simple Changes, Big Differences -- Crystal Packing and Effect of a Twist

2.4.9 Introducing Polar Clashes to Induce a Twist -- 2.4.10 Profound Effect of Methyl Substituents -- 2.4.11 Additions of a Solubilising Group -- 2.4.12 Salt Formation -- References -- Chapter 3 Optimisation of Passive Permeability for Oral Absorption -- 3.1 Introduction -- 3.1.1 Potential Mechanisms of Membrane Permeation -- 3.1.2 Strategies for Screening for Passive Permeability -- 3.1.3 Influence of Physicochemical Properties on Passive Permeability -- 3.1.4 Future Directions: Beyond Rule-of-five -- 3.1.5 Relevance -- 3.2 Mitigation Strategies -- 3.3 Examples of Mitigation Strategies

The Medicinal Chemist's Guide to Solving ADMET Challenges presents state-of-the-art design strategies by a global group of experienced medicinal chemists and ADMET experts across academia and the pharmaceutical industry.

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