Author Description

This Practical Reference For Medicinal And Pharmaceutical Chemists Combines The Theoretical Background With Modern Methods As Well As Applications From Recent Lead Finding And Optimization Projects. Divided Into Two Parts On The Thermodynamics And Kinetics Of Drug-receptor Interaction, The Text Provides The Conceptual And Methodological Basis For Characterizing Binding Mechanisms For Drugs And Other Bioactive Molecules. It Covers All Currently Used Methods, From Experimental Approaches, Such As Itc Or Spr, Right Up To The Latest Computational Methods. Case Studies Of Real-life Lead Or Drug Development Projects Are Also Included So Readers Can Apply The Methods Learned To Their Own Projects. Finally, The Benefits Of A Thorough Binding Mode Analysis For Any Drug Development Project Are Summarized In An Outlook Chapter Written By The Editors.-- Keserü 4.1 Introduction 63 4.2 Thethermodynamics Of Medicinal Chemistry Optimizations 66 4.3 Selection Of Suitable Starting Points 70 4.4 Thermodynamics Based Optimization Strategies 73 References 78 5 From Molecular Understanding To Structure-thermodynamic Relationships, The Case Of Acetylcholine Binding Proteins 81; Antoni R. Blaazer And Iwan J. P. De Esch 5.1 Introduction 81 5.1.1 Natural Nachr Ligands 82 5.1.2 Nachr Ligands As Therapeutic Agents 83 5.2 Acetylcholine Binding Proteins (achbps) 85 5.3 Thermodynamics Of Small Molecule Binding At Achbps 89 5.4 Concluding Remarks And Outlook 98 References 99 6 Thermodynamics In Lead Optimization 107; Geoffrey A. Holdgate, Andrew Scott, And Gareth Davies 6.1 Introduction To Lead Optimization In Drug Discovery 107 6.2 Measurement Ofthermodynamic Parameters In Lead Optimization 111 6.3 Advantages During Lead Optimization For Thermodynamic Measurements 117 6.4 Exploitation Of Measured Thermodynamics In Lead Optimization 118 6.5 Lead Optimization Beyond Affinity 120 6.6 Exemplary Case Studies 123 6.7 Potential Complicating Factors In Exploiting Thermodynamics In Lead Optimization 12