Cyclic sulfoxides and sulfones in drug design

The present review mainly focuses on discussing lead compounds and drugs that contain cyclic sulfoxide and sulfone moieties together with appropriate consideration of the structure–activity relationships (SARs). Cyclic sulfoxides and sulfones have been found to function as important pharmacophores that are responsible for the biological activity toward a range of targets across many therapeutic areas. In particular, the sulfone is a polar moiety that offers many useful properties, including lowering the lipophilicity of a molecule, which can help to increase solubility and metabolic stability and lead to an overall improvement of ADME (absorption, distribution, metabolism and excretion) properties. In this chapter, cyclic sulfoxides and sulfones are discussed with respect to their ability to act as conformational constraints, H-bond acceptor and electron-withdrawing elements, including application as bioisosteres of ketone and carboxylic acid functionalities. In addition, the sulfone moiety can reduce the basicity of proximal amines, leading to modulation of their overall basicity and, in many cases, improving the toxicity profile. This review outlines some of the recent examples of applications of cyclic sulfoxides and sulfones in medicinal chemistry. In addition, we highlight the roles that the cyclic sulfones play in preclinical and clinical compounds and marketed drugs.