Small Bicyclic Amines: Unexplored Motifs for Drug Discovery

点击翻译按钮获取中文摘要

Substituents and scaffolds that can beneficially alter physicochemical properties and/or explore novel vectors can have transformative potential in medicinal chemistry, delivering molecules with improved selectivity profiles and hence safer, more effective drugs. In this project, we introduce small bicyclic amines (SBAs) as unusual and underexplored motifs that, when linked to (hetero)aryl groups, remain pyramidalised at nitrogen. This not only creates new 3D vectors for exploration but also has a positive impact on the physicochemical and metabolic properties of the molecules, which can lead to more effective and selective drug molecules. In this programme, will introduce SBAs as a new motif for medicinal chemistry by (a) developing scalable chemical synthetic routes to SBAs; (b) optimising chemical catalytic methods for their arylation; (c) characterising and understanding physicochemical and structural properties of arylated SBAs, including the use of data-driven approaches to understand and predict properties; and (d) demonstrating positive impact on the properties of small molecule bioactives.The work directly addresses challenges in improving human health and so addresses the EPSRC theme of Healthcare Technologies, specifically the grand challenge of "developing new therapies". It contains technical elements relevant to EPSRC research areas of Chemical Biology and Biological Chemistry, Synthetic Organic Chemistry and Catalysis.