3-hydroxycyclopent-1-enecarboxylic-acid has been researched along with 4-hydroxybutyric-acid* in 3 studies
3 other study(ies) available for 3-hydroxycyclopent-1-enecarboxylic-acid and 4-hydroxybutyric-acid
| Article | Year |
|---|---|
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.
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 molecular 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 diaromatic substituents into the 4-position of T-HCA led to high-affinity analogs (medium nanomolar K Topics: Binding Sites; Carboxylic Acids; Crotonates; Cyclopentanes; Drug Design; Hydroxybutyrates; Ligands; Models, Molecular; Molecular Conformation; Structure-Activity Relationship | 2017 |
Autoradiographic imaging and quantification of the high-affinity GHB binding sites in rodent brain using
GHB (γ-hydroxybutyric acid) is a compound endogenous to mammalian brain with high structural resemblance to GABA. GHB possesses nanomolar-micromolar affinity for a unique population of binding sites, but the exact nature of these remains elusive. In this study we utilized the highly selective GHB analogue, 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) as a tritiated version ( Topics: Animals; Autoradiography; Binding Sites; Binding, Competitive; Brain; Carboxylic Acids; Cyclopentanes; Hydroxybutyrates; Mice; Radioligand Assay; Rodentia | 2016 |
New synthesis and tritium labeling of a selective ligand for studying high-affinity γ-hydroxybutyrate (GHB) binding sites.
3-Hydroxycyclopent-1-enecarboxylic acid (HOCPCA, 1) is a potent ligand for the high-affinity GHB binding sites in the CNS. An improved synthesis of 1 together with a very efficient synthesis of [(3)H]-1 is described. The radiosynthesis employs in situ generated lithium trimethoxyborotritide. Screening of 1 against different CNS targets establishes a high selectivity, and we demonstrate in vivo brain penetration. In vitro characterization of [(3)H]-1 binding shows high specificity to the high-affinity GHB binding sites. Topics: Animals; Benzocycloheptenes; Binding Sites; Binding, Competitive; Brain; Carboxylic Acids; Cell Line; Central Nervous System; Cyclopentanes; Drug Stability; gamma-Aminobutyric Acid; Hydroxybutyrates; Kinetics; Ligands; Male; Models, Chemical; Molecular Structure; Radioligand Assay; Rats; Rats, Sprague-Dawley; Synaptic Membranes; Tritium | 2013 |