Design polar surface area

Ertl, P., Rohde, B., Selzer, P. Calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. In Rational Approaches to Drug Design, Holtje, H.-D., Sippl, W. (eds.), Prous, Barcelona, 2001, pp. 4514 55. 

Absorption, in general, is treated as a physicochemical transport process based on computations of logP (the octanol/water partition coefficient) and solubility governed by factors such as polar surface area on the molecule. It is conceivable that SNPs in drug transporter genes will affect the pharmacokinetic properties of compounds and, therefore, these may have to be taken into consideration in the design process. 

Quantitative structure-activity relationship Root mean square error Receiver-operating characteristic Recursive partitioning Support vector machine TOPological Substructural Molecular Design Topological polar surface area... 

Another property filter designed to predict oral bioavailability was proposed by [Veber, Johnson et al, 2002] by substituting the four Lipinski rules with the following two rules (a) number of rotatable bonds <10, and (b) polar surface area (PSA) < 140 or the sumof H-bond acceptors and H-bond donors <12. 

The descriptor uses readily calculable physicochemical properties from the topological structure. The descriptors used in this study were atomic weight, hydropho-bicity, molecular refractivity, atomic charge, polar surface area, hydrogen bond acceptors, and hydrogen bond donors. The authors note that Martin et al. [32] applied a similar approach for the design of diverse combinatorial libraries. 

---