Comparative spectra analysis (CoSA): Spectra as three-dimensional molecular descriptors for the prediction of biological activities

A novel 3D QSAR approach, comparative spectra analysis (CoSA), in which mol ecular spectra are used as three-dimensional molecular descriptors for the prediction of biological activities, is presented and discussed. To this pu rpose, experimentally determined H-1 NMR, mass, and IR spectra, as well as simulated IR and C-13 NMR spectra, for a set of 45 diverse progestagens are converted by a program, SpecMat, into matrixes, which are subsequently emp loyed in a multivariate regression analysis (PLS). The results are compared with those resulting from a comparative molecular field analysis (CoMFA). When used individually, spectral descriptors yield better correlations and predictions than molecular field descriptors. A combination of spectral des criptors with other descriptors, either spectral or molecular field in natu re, leads in most cases to models that are statistically superior to the on es obtained by their corresponding individual spectral or molecular field d escriptors.