The impact of aromatic ring count on compound developability – are too many aromatic rings a liability in drug design?

Stephen Carney

The content of the most downloaded article in Q4 2009 deals with the impact of the number of aromatic rings on the ability to deliver quality compounds for drug development. This information and analysis is clearly highly important and directly relevant to the day-to-day work of the medicinal chemist.

The impact of aromatic ring count (the number of aromatic and heteroaromatic rings) in molecules has been analyzed against various developability parameters – aqueous solubility, lipophilicity, serum albumin binding, CyP450 inhibition and hERG inhibition. On the basis of this analysis, it was concluded that the fewer aromatic rings contained in an oral drug candidate, the more developable that candidate is probably to be; in addition, more than three aromatic rings in a molecule correlates with poorer compound developability and, thus, an increased risk of attrition in development. Data are also presented that demonstrate that even within a defined lipophilicity range, increased aromatic ring count leads to decreased aqueous solubility.

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Medicinal Chemistry


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