Krall, Jacob; Jensen, Claus Hatt; Bavo, Francesco; Falk-Petersen, Christina Birkedal; Haugaard, Anne Staehr; Vogensen, Stine Byskov; Tian, Yongsong; Nittegaard-Nielsen, Mia; Sigurdardottir, Sara Bjork; Kehler, Jan; Kongstad, Kenneth Thermann; Gloriam, David E.; Clausen, Rasmus Praetorius; Harpsoee, Kasper; Wellendorph, Petrine; Froelund, Bente published the artcile< Molecular Hybridization of Potent and Selective γ-Hydroxybutyric Acid (GHB) Ligands: Design, Synthesis, Binding Studies, and Molecular Modeling of Novel 3-Hydroxycyclopent-1-enecarboxylic Acid (HOCPCA) and trans-γ-Hydroxycrotonic Acid (T-HCA) Analogs>, Recommanded Product: (9Z,12Z)-Methyl octadeca-9,12-dienoate, the main research area is hydroxybutyric acid ligand preparation binding affinity structure activity relationship; mol modeling hydroxybutyric acid ligand; hydroxycyclopentenecarboxylic acid analog preparation GHB ligand high affinity; hydroxycrotonic acid analog preparation GHB ligand high affinity.
γ-Hydroxybutyric acid (GHB) is a neuroactive substance with specific high-affinity binding sites. To facilitate target identification and ligand optimization, we herein report a comprehensive structure-affinity relationship study for novel ligands targeting these binding sites. A mol. hybridization strategy was used based on the conformationally restricted 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) and the linear GHB analog trans-4-hydroxycrotonic acid (T-HCA). In general, all structural modifications performed on HOCPCA led to reduced affinity. In contrast, introduction of diarom. substituents into the 4-position of T-HCA led to high-affinity analogs (medium nanomolar Ki) for the GHB high-affinity binding sites as the most high-affinity analogs reported to date. The SAR data formed the basis for a three-dimensional pharmacophore model for GHB ligands, which identified mol. features important for high-affinity binding, with high predictive validity. These findings will be valuable in the further processes of both target characterization and ligand identification for the high-affinity GHB binding sites.
Journal of Medicinal Chemistry published new progress about Molecular modeling. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Recommanded Product: (9Z,12Z)-Methyl octadeca-9,12-dienoate.
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