Exploration of 3-D Pharmaceutical Space: sp3-sp2 Cross-Coupling and Fragment-Based Drug Discovery

The O’Brien group is motivated by the development of new synthetic methodology for exploring 3-D pharmaceutical space. This is because there is a growing demand within medicinal chemistry for methods that enable 3-D compounds to be readily synthesised and joined together. This talk will focus on two different projects within our group. First, the development of Pd-catalysed sp3-sp2 Suzuki-Miyaura cross-coupling of heterocyclic organoboron compounds on a range of substrates of relevance to medicinal chemistry will be presented. Focus will be on the optimisation, scope and stereochemical outcome of these reactions. Second, within the context of fragment-based drug discovery, the development of a modular synthetic platform for the elaboration of 2-D fragments hits into 3-D lead-like compounds will be discussed. This will focus on a set of novel cyclopropane and cyclobutane 3-D building blocks together with a case study on the development of a nM inhibitor of JAK3.