Physics

Chiral symmetry breaking

Stereochemistry

Biology

Enantioselective synthesis

Chirality (physics)

Catalysis

Axial chirality

Nambu–Jona-Lasinio model

Atropisomer

Chemistry

Quantum mechanics

Computational biology

Drug discovery

Biochemistry

Quark

Future Medicinal Chemistry

Atropisomerism is a dynamic type of axial chirality that is ubiquitous in medicinal chemistry. There are several examples of stable atropisomeric US FDA-approved drugs and experimental compounds, and in each case the atropisomers of these compounds possess drastically different biological activities. Rapidly interconverting atropisomerism is even more prevalent, and while such compounds are typically considered achiral, they bind their protein targets in an atroposelective fashion, with the nonrelevant atropisomer contributing little to the desired activities. It has been recently demonstrated that various properties of an interconverting atropisomer can be modulated through the synthesis of atropisomer stable and pure analogs. Herein we discuss examples of atropisomerism in drug discovery as well as challenges and opportunities moving forward.

Atropisomerism in Medicinal Chemistry: Challenges and Opportunities