Characterisation and analysis of beta-aminoketones as potential prodrugs for amines

Abstract

The aim of the work described in this thesis is to evaluate the potential of β-aminoketones as amine prodrugs. These compounds are usually stable in acidic conditions while they cleave into the parent amine and an α,β-unsaturated ketone at neutral to basic pH. The rates of liberation of the amine may be suitable for application of these compounds as prodrugs. Chapter 1 describes the principal strategies normally used for the design of prodrugs. Published approaches to amine prodrugs are described with particular detail. Chiral and achiral methods were developed for the analysis of certain β-aminoindanones and related compounds. This work, which is described in Chapter 2, lead to the discovery that some β-aminoindanones degrade, in physiological conditions, at rates consistent with their application as prodrugs for amines. In Chapter 3 the kinetic tests performed on new β-aminoindanones are described. This confirms the applicability of the system to a wider range of primary and secondary amines.