The presentation addresses the pharmaceutical implications of a largely overlooked alternative source of drug chirality � atropisomerism, which has the distinct feature of creating molecular chirality as a result of hindered rotation about a bond axis.  Due to this time-dependent feature, drug discovery campaigns have notoriously become more complex or even abandoned.  A variety of chemotypes will be presented as an aid for flagging atropisomeric compounds, along with computational and experiment tools for predicting and revealing their existence.  Once identified, medicinal chemists have multiple options that range from avoiding atropisomerism to designing compounds that rotate faster or slower, with the goal of preparing for development requirements.  A categorization scheme is proposed as a guide to help bridge the efforts of chemists at the early drug discovery stages with later efforts of development scientists.  Overall, this presentation emphasizes the view that atropisomeric compounds can be successfully developed with caution and proper management.

Assessing atropisomer axial chirality in drug discovery and development

244th National Meeting (2012)

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