Drug-Like Properties (2^nd Ed.)
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 successfully complete human Phase I clinical trials. Drug-Like Properties: Concepts, Structure Design and Methods from ADME to Toxicity Optimization, Second Edition, provides scientists and students the background and tools to understand, discover, and develop optimal clinical candidates. This valuable resource explores physiochemical properties, including solubility and permeability, before exploring how compounds are absorbed, distributed, and metabolized safely and stably. Review chapters provide context and underscore the importance of key concepts such as pharmacokinetics, toxicity, the blood-brain barrier, diagnosing drug limitations, prodrugs, and formulation. Building on those foundations, this thoroughly updated revision covers a wide variety of current methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties for process and product improvement. From conducting key assays for interpretation and structural analysis, the reader learns to implement modification methods and improve each ADME property.

Through valuable case studies, structure-property relationship descriptions, and structure modification strategies, Drug-Like Properties, Second Edition, offers tools and methods for ADME/Tox scientists through all aspects of drug research, discovery, design, development, and optimization.

1. Introduction2. Benefits of Property Assessment and Good Drug-Like Properties3. In Vivo Environments Affect Drug Exposure4. Prediction Rules for Rapid Property Profiling from Structure5. Lipophilicity6. pK_a7. Solubility8. Permeability9. Transporters10. Blood-Brain Barrier11. Metabolic Stability12. Plasma Stability13. Solution Stability14. Plasma and Tissue Binding15. Cytochrome P450 Inhibition16. hERG Blocking17. Toxicity18. Integrity and Purity19. Pharmacokinetics20. Lead Properties21. Strategies for Integrating Drug-Like Properties into Drug Discovery22. Methods for Profiling Drug-Like Properties: General Concepts23. Lipophilicity Methods24. pK_a Methods25. Solubility Methods26. Permeability Methods27. Transporter Methods28. Blood-Brain Barrier Methods29. Metabolic Stability Methods30. Plasma Stability Methods31. Solution Stability Methods32. CYP Inhibition Methods33. Plasma and Tissue Binding Methods34. hERG Methods35. Toxicity Methods36. Integrity and Purity Methods37. Pharmacokinetic Methods38. Diagnosing and Improving Pharmacokinetic Performance39. Prodrugs40. Effects of Properties on Biological Assays41. Formulation

• Provides a comprehensive and valuable working handbook for scientists and students in medicinal chemistry
• Includes expanded coverage of pharmacokinetics fundamentals and effects
• Contains updates throughout, including the authors’ recent work in the importance of solubility in drug development; new and currently used property methods, with a reduction of seldom-used methods; and exploration of computational modeling methods