Atropisomerism in Drug Discovery and Development

Abstract

Atropisomerism, the phenomenon of stable stereoisomerism due to hindered rotation around a single bond, plays a crucial role in modern drug discovery and development. This chapter provides a comprehensive overview of atropisomerism in the context of drug design, highlighting its impact on the synthesis and separation of atropisomeric drugs as well as their varying biological activities. It analyzes atropisomeric drugs in the pharmaceutical market, classifying them based on rotational energy barriers. Various classes of atropisomeric compounds, including biaryls, heterobiaryls, diaryl ethers, diaryl amines, benzamides, and macrocycles, are discussed, along with examples of FDA-approved drugs exhibiting atropisomerism. Additionally, this chapter explores the use of atropisomerism to modulate selectivity in drug targets and addresses the challenges associated with manufacturing pure atropisomers.