3D-Quantitative structure–activity relationship and docking studies of the tachykinin NK3 receptor

The tachykinin NK3 receptor (NK3R) 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 NK3 antagonist compounds. We developed a 3D comparative molecular similarity index analysis (CoMSIA) model that gave cross-validated PLS values with q2 >0.5 which were validated using a test set. We also describe the development of a homology model of the NK3R. 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 NK3R.

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