CHAPTER 6: HIV Integrase Inhibitors

This chapter presents the discovery, development and evolution of integrase strand transfer inhibitors. A brief overview of the first‐generation inhibitors raltegravir and elvitegravir serves to describe their landmark advancement of the field and also outline areas for further improvement. The remainder of the discussion revolves around the strategy in designing a series of carbamoylpyridines that ultimately led to the discovery of dolutegravir, an investigational integrase inhibitor in late‐stage clinical development. In addition, an intriguing approach to the development of a related compound, S/GSK744, as a long‐acting parenteral agent is presented. Finally, an exciting new area of non‐catalytic site integrase inhibitors is included.