A TOPS-MODE approach to predict adenosine kinase inhibition

The TOPological Sub-Structural Molecular Design (TOPS-MODE) approach has been applied to the study of the adenosine kinase inhibitory activity of pyrrolo[2,3-d]pyrimidine nucleoside analogues. A model capable of describing around 77% of the variance in the experimental activity of 32 analogues of these compounds was developed with the use of the mentioned approach. In contrast, no one of nine different approaches, including the use of Constitutional, Topological, BCUT, 2D autocorrelations, geometrical, RDF, 3D Morse, WHIM, and GETAWAY descriptors were able to explain more than 70% of the variance in the mentioned property with the same number of descriptors. Although, statistically significant models were derived containing other descriptors than spectral moments still the best one fitted out model was find with these variables.