Small Bicyclic Amines: Unexplored Motifs for Drug Discovery

取代基和支架可以有益地改变物理化学性质和/或探索新的载体，可以在药物化学中具有转化潜力，提供具有更高选择性的分子，从而提供更安全、更有效的药物。在这个项目中，我们引入了小的双环胺(SBAs)作为不寻常的和未被探索的基序，当它与(杂)芳基连接时，在氮气中保持金字塔化。这不仅为探索创造了新的3D载体，而且对分子的物理化学和代谢性质产生了积极的影响，从而可以导致更有效和更具选择性的药物分子。在这项计划中，将通过(A)开发可扩展的化学合成路线来引入SBAs作为药物化学的新主题；(B)优化其芳基化的化学催化方法；(C)表征和了解芳基化SBAs的物理化学和结构特性，包括使用数据驱动的方法来了解和预测特性；以及(D)展示对小分子生物活性特性的积极影响。这项工作直接解决了改善人类健康的挑战，从而解决了EPSRC的医疗技术主题，特别是“开发新疗法”的重大挑战。它包含与EPSRC研究领域相关的技术要素，如化学生物学和生物化学、合成有机化学和催化。

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.