Timothy John Ritchie

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

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.

Analysis of the calculated physicochemical properties of respiratory drugs: can we design for inhaled drugs yet?

From an analysis of calculated physicochemical properties for 81 currently marketed respiratory drugs, compounds administered via the inhaled/intranasal routes have a higher polar surface area, a higher molecular weight, and a trend toward lower lipophilicity, when compared with their orally administered counterparts. Ranges of physicochemical space are described for the 29 drugs administered by the inhaled or intranasal routes.