What does the aromatic ring number mean for drug design?

INTRODUCTION: During the last decade, there has been an increased focus on understanding the factors that influence the chance of success of a drug molecule in development. Recent publications have highlighted that the aromatic ring count of a drug molecule also has an influence on its developability profile. AREAS COVERED: This article reviews both the positive and negative consequences of including aromatic rings in drug molecules based on the recent literature and presents a thorough review of recent publications describing the influence of aromatic ring count on compound developability. These conclusions are analysed alongside their implications for the medicinal chemist. The authors also highlight the limitations of recent analyses; this includes a particular emphasis on the restricted diversity of the compound collections used. EXPERT OPINION: Modern medicinal chemists work in a very restricted area of the available drug-like chemical space, although there is evidence that safe compounds can be identified outside of conventional drug-like chemical space. It is true that current evidence implies that drug molecules with > 3 aromatic rings in are undesirable and that heteroaromatics perform better than carboaromatic overall. However, the analyses performed so far have only used compounds designed for oral administration, which were provided from pharmaceutical companies' collections, and were therefore limited in diversity.