A library of 23 pyrazolo-pyrimidine compounds Src tyrosine kinase (TK) inhibitors, that reduced proliferation of a human osteogenic sarcoma cell line, was taken to investigate lack of correlation between inhibition of cellular viability (CV%) and enzymatic inhibition constants (K(i) Src). With the aim of understanding this behaviour, we focused on physico-chemical parameters which characterize partition coefficient and diffusion through membrane. Parallel artificial membrane permeability assay (PAMPA) has been frequently used for the evaluation of in vitro permeability of new chemical entities and, in this paper, a new approach for determining permeability of low soluble compounds was obtained. Goodness of PAMPA methodology was confirmed by logK(w) and computational approaches, by VolSurf, Cerius(2) and QikProp software programs. The results suggest that the lipophilicity and passive diffusion across the membranes do not significantly influence the activity of the compounds. This trend can be explained by a different target for some of the compounds in our set. In fact some compounds resulted also to be active toward Abl enzyme, another cytoplasmatic TK.