Application of similarity matrices and genetic neural networks in quantitative structure-activity relationships of 2-or 4-(4-methylpiperazino)pyrimidines: 5-HT2A receptor antagonists

Antagonists of the 5-HT2A receptor are being used to treat many psychiatric disorders. The present work focuses on a group of 27 antagonists possessin g varying affinities toward the receptor. These are 26 title compounds and clozapine as a reference antagonist. The active conformers of the conformat ionally flexible ligands were proposed by using the active rigid analogue a pproach and performing similarity calculations. The calculations involved g enetic neural network (GNN) computations deriving QSARs from similarity mat rices (SM) with cross-validated correlation coefficients exceeding 0.92. Th e performance of neural networks with variety of architectures was studied. As the computations were performed for cations and neutral molecules separ ately, the relevance of the ligand charging is discussed.