NEW PERSPECTIVES ON MACROCYCLES FOR DRUG DISCOVERY
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Diverse Macrocycle Synthesis

Abstract: The pharmaceutical industry is an enormously successful business sector. However, the current challenges facing the industry are unprecedented. Foremost among these challenges are the industry's diminishing revenue forecasts due to the decreasing number of new chemical entity (NCE) approvals. A high attrition rate of clinical candidates (ca. 93-96%) is prevalent throughout the industry. Pharma's recent dramatic restructuring is largely due to this high attrition rate. My talk aims to highlight some of the underlying factors of this. Namely, (1) the relative lack of structural diversity and (2) the relative lack of targets exploited in drug discovery. The talk will include recent research within my laboratory aimed at addressing these issues, specifically diverse macrocycle library synthesis.


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David Spring
Yusuf Hamide Department of Chemistry, University of Cambridge, UK
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Related publications:
Strategies for the Diversity-Oriented Synthesis of Macrocycles, K. T. Mortensen, T. J. Osberger, T. A. King, H. F. Sore, D. R. Spring, Chem. Rev. 2019, 119, 10288-10317.
A Multidimensional Diversity-Oriented Synthesis Strategy for Structurally Diverse and Complex Macrocycles, F. Nie, D. L. Kunciw, D. Wilcke, J. E. Stokes, W. R. J. D. Galloway, S. Bartlett, H. F. Sore, D. R. Spring, Angew. Chem. Int. Ed. 2016, 55, 11139-11143.
A New Strategy for the Diversity-Oriented Synthesis of Macrocyclic Scaffolds using Multi-Dimensional Coupling, H. S. G. Beckmann, F. Nie, C. E. Hagerman, H. Johansson, Y. S. Tan, D. Wilcke, D. R. Spring, Nature Chem. 2013, 5, 861-867.
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