Synthesis and functionalisation of heterocyclic molecules with bioactive properties

Heterocycles are one of the most important class of molecules in medicinal chemistry. These compounds comprise a vast amount of the bioactive molecules available and provide biological activity over a huge range of targets. This work strives to develop novel drug candidates to target different diseases, utilising structure-activity relationship data and the results of biological testing to guide synthesis. The ultimate aim is to discover lead drug candidates that could advance to clinical trials and are readily accessible. Part One of this thesis discusses the synthesis of thiophenes and preliminary studies investigating their capacity to act as PAF receptor antagonists. More than 40 diseases and disorders are associated with the inflammatory actions of PAF and its receptor. Antagonists can be used to control these inflammatory responses. Existing antagonists suffer from difficult and lengthy syntheses. A range of 2-pyrrolothiophenes were prepared via an efficient 2-step pathway. A number of these analogues showed excellent activity and potency as PAFr antagonists in vitro, with no toxic effects observed in initial tests up to concentrations of 100 μm. A range of thienoquinolines were also synthesised, via a rapid and highly efficient route. In preliminary in vitro results, a number of these new molecules have exhibited selective and potent anti-giardial activity (