Estimation of blood-brain barrier crossing of drugs using molecular size and shape, and H-bonding descriptors

The influence of physicochemical properties, including lipophilicity, H-bon ding capacity and molecular size and shape descriptors on brain uptake has been investigated using a selection of marketed CNS and CNS-inactive drugs, It is demonstrated that the polar surface area of a drug can be used as a suitable descriptor for the drugs' H-bonding potential. A combination of a H-bonding and a molecular size descriptor, i.e,, the major components of li pophilicity and permeability, avoiding knowledge of distribution coefficien ts, is proposed to estimate brain penetration potential of new drug candida tes. Previously reported experimental surface activity data appear to be st rongly correlated to molecular size of the drug compounds. Present analysis offers a modern basis for property-based design and targeting of CNS drugs .