Chapter 6. Influence of Aromatic Rings on ADME Properties of Drugs
Deepak Dalvie, Sajiv K. Nair, Ping Kang, Cho‐Ming Loi · RSC drug discovery/RSC drug discovery series · 2010
Aromatic heterocycles play a critical role in medicinal chemistry and drug design. More than half of the known drugs contain at least one heterocyclic component in their structure. The electronic properties of heterocyclic rings are such that introduction of these rings into drug molecules can affect their physicochemical properties. These in turn can affect their absorption, distribution, metabolism and excretion and toxicity (ADMET) profiles. This chapter describes the influence of heteroaromatic rings on ADME properties of the molecule. An attempt has been made to correlate the effect of the change in the physicochemical properties such as lipophilicity (logP/logD), acidity/basicity (pKa), hydrogen bonding capability of molecules and polar surface area (PSA) on their ADME properties. The examples presented in this review illustrate that incorporation of heteroaromatic rings in a compound can have major effect on its disposition in the body.