Abstract

Polyfunctional pyrroles are interesting heterocyclic intermediates as they have a range of reactive centres and the chemoselectivity of their reactions under a range of conditions, is therefore, of much interest. Polyfunctionalised heterocycles are relatively difficult to prepare, but the reactions of these substituted pyrroles allow access to a wide variety of new substituted heterocyclic compounds via these intermediates.
The aim of this project was to synthesise polyfunctional pyrroles in order to investigate their use in the preparation of libraries and compounds with known biological activity. The synthesis and initial investigation of the regioselectivity of polyfunctional pyrroles, such as 3,5-dichloro-1H-pyrrole-2,4-dicarboxaldehyde, has previously been described; this work investigated only nucleophilic substitutions. We have investigated the chemoselectivity of the reaction of these pyrroles with a range of reagents and a number of pyrrole derivatives were synthesised via selective functional group transformations. All new compounds were fully characterised by spectroscopic and elemental analysis.
Another aim of this project was to discover novel agents that inhibit VEGF receptors using structure based drug design. We have identified hit compounds and synthesised them using regioselective reactions of functional groups present on the pyrrole ring. The compounds were tested for anti-proliferative activity against the HaCaT, human keratinocyte cell line, and also against HT29 and CaCo-2, human colon cell lines using the MTT assay.