The Application of Fragment-based Approaches to the Discovery of Drugs for Neglected Tropical Diseases

The term neglected tropical disease (NTD) is used to describe a diverse collection of communicable diseases prevalent in tropical and subtropical regions, which predominantly affect the poor. This chapter describes how fragment-based approaches are being applied in projects aimed at the discovery of new drugs for NTDs, either alone or in conjunction with high-throughput screening. It presents examples, classified according to pathogen, to highlight the power of fragment-based approaches to reveal binding hot-spots and novel allosteric binding sites, and to identify efficient starting points for drug discovery. The chapter also shows how fragment-based approaches can facilitate optimization of hits identified by other means and enable careful control of drug-like properties during the optimization of a chemical series. Fragment-based approaches, although target-based, have the key advantages that libraries are smaller and more efficiently explore chemical space, and more careful control of physicochemical properties is possible during optimization.