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Atropisomerism in medicinal chemistry: challenges and opportunities.

ABSTRACT: 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.

SUBMITTER: Toenjes ST

PROVIDER: S-EPMC5967358 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Atropisomerism in medicinal chemistry: challenges and opportunities.

Toenjes Sean T ST Gustafson Jeffrey L JL

Future medicinal chemistry 20180130 4

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 nonr ...[more]

PMID: 29380622

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