A quantitative structure-activity relationship approach to the minimization of albumin binding.

The binding of 2,6-disubstituted xanthones to human serum albumin (HSA) has been investigated using an ultrafiltration technique. A set of 26 compounds was chosen for study using a selection procedure aimed at minimizing the interparameter correlations, while ensuring that the physicochemical properties covered the maximum possible range of values. The magnitude of binding has been expressed as the compound concentration required to produce a specified bound concentration, in preference to equilibrium constants and number of albumin binding sites. Albumin binding was found to have a nonlinear dependence on the octanol-water partition coefficient (log P) and has been rationalized in terms of a simple binding model.