Synthesis of novel pyrazolopyrimidines

Abstract

Prazolo[1,5a]pyrimidines have been used as the core structure in several drugs and bioactive molecules. These compounds can be used to treat various diseases by acting on enzymes or regulating protein function in organisms. For example, Zaleplon, which is a sedative, can treat sleeplessness by modulating GABAA receptor sites.

This project focused on compounds which include the pyrazolo[1,5a]pyrimidine core structure which could potentially work as modulators of protein-protein interactions associated with a protein known as reptin.

Chapter 1 introduces background information on protein-protein interactions associated with reptin and then briefly summarises current efforts to find and optimise molecules including pyrazolo[1,5-a]pyrimidines that affect reptin’s protein-protein interactions. An overview of the available methods to prepare pyrazolo[1,5-a]pyrimidines is provided.

Chapter 2 summarises the 7 analogues which were designed to be synthesised using 4 different approaches.

In Chapter 3 the results of this project are discussed. The first synthetic route was used to obtain 3 analogues. A key hydrolysis reaction in this approach has been optimised. A second approach was used to obtain a further 2 analogues, however, the conditions of the Suzuki cross-coupling reaction probably require further optimisation. The third approach was used to synthesise further 1 analogue. This analogue included a Cl group which is easy to change to other group to obtain further 2 analogues. The fourth synthetic approach was initially planned to synthesise 2 analogues, but because one of the steps was unsuccessful, this approach will have to be changed to enable the synthesis of these 2 analogues.

Chapter 4 provides a summary of the results that were obtained and the thesis concludes with a discussion in Chapter 5 of potential future work.