title: Application of similarity matrices and genetic neural networks in quantitative structure-activity relationships of 2- or 4-(4-Methylpiperazino)pyrimidines: 5-HT(2A) receptor antagonists.
abstract: Antagonists of the 5-HT(2A) receptor are being used to treat many psychiatric disorders. The present work focuses on a group of 27 antagonists possessing varying affinities toward the receptor. These are 26 title compounds and clozapine as a reference antagonist. The active conformers of the conformationally flexible ligands were proposed by using the active rigid analogue approach and performing similarity calculations. The calculations involved genetic neural network (GNN) computations deriving QSARs from similarity matrices (SM) with cross-validated correlation coefficients exceeding 0.92. The performance of neural networks with variety of architectures was studied. As the computations were performed for cations and neutral molecules separately, the relevance of the ligand charging is discussed.
authors.affiliation: Department of Theoretical Chemistry, Faculty of Chemistry, Jagiellonian University, 30-060 Kraków, Ingardena 3, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Borowski
authors.forename: M
authors.initials: M
authors.lastname: Król
authors.forename: E
authors.initials: E
authors.lastname: Broclawik
authors.forename: T C
authors.initials: TC
authors.lastname: Baranowski
authors.forename: L
authors.initials: L
authors.lastname: Strekowski
authors.forename: M J
authors.initials: MJ
authors.lastname: Mokrosz
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D003024:Clozapine / Q000378:metabolism; D007650:Ketanserin / Q000378:metabolism; D008024:Ligands; D008433:Mathematics; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D016571:Neural Networks, Computer; D011743:Pyrimidines / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D011743:Pyrimidines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D007650:Ketanserin; D003024:Clozapine