title: 3D-Quantitative structure-activity relationship and docking studies of the tachykinin NK3 receptor.
abstract: The tachykinin NK(3) receptor (NK(3)R) is a novel drug target for schizophrenia and drug abuse. Since few non-peptide antagonists of this G protein-coupled receptor are available, we have initiated this study to gain a better understanding of the structure-activity relationships of NK(3) antagonist compounds. We developed a 3D comparative molecular similarity index analysis (CoMSIA) model that gave cross-validated PLS values with q(2) >0.5 which were validated using a test set. We also describe the development of a homology model of the NK(3)R. The model was then used to develop a pharmacophore for docked ligands. This pharmacophore showed two aromatic, two hydrogen donor and one acceptor/aromatic points. These data will be useful for future structure-based drug discovery of ligands for the NK(3)R.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
authors: Werner J
authors: WJ
authors: Geldenhuys
authors: Mark A
authors: MA
authors: Simmons
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D021281:Quantitative Structure-Activity Relationship; D011804:Quinolines / Q000737:chemistry; D018042:Receptors, Neurokinin-3 / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008024:Ligands; D011804:Quinolines; D018042:Receptors, Neurokinin-3; C037219:quinoline