Design and structure-activity relationship analysis of ligands of gamma-hydroxybutyric acid receptors.
With the use of [3H]gamma-hydroxybutyric acid, binding experiments allowed the screening of new compounds as ligands of gamma-hydroxybutyric acid receptors. Starting from the acid-alcohol gamma-hydroxybutyric acid structure, structure-activity relation analysis and lead optimization highlighted gamma-hydroxybutyric acid derivatives with significantly increased affinities, when compared with the affinity of gamma-hydroxybutyric acid. Further pharmacological studies with the use of gamma-hydroxybutyric acid derivatives allowed the characterization of the first competitive antagonist acting at gamma-hydroxybutyric acid receptors (NCS 382).
Bourguignon
J J
JJ
Laboratoire de Pharmacochimie de la Communication Cellulaire, ERS 655 du CNRS, Faculté de Pharmacie, 74 route du Rhin, B.P. 21, 67401, Illkirch, France. jjb@pharma.u-strasbg.fr
Schmitt
M
M
Didier
B
B
D001567:Benzocycloheptenes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D006885:Hydroxybutyrates / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008968:Molecular Conformation; D015394:Molecular Structure; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014316:Tritium
C039403:4-hydroxybutyric acid receptor; D001567:Benzocycloheptenes; D006885:Hydroxybutyrates; D008024:Ligands; D011956:Receptors, Cell Surface; D014316:Tritium; C066471:NCS 382; C111420:4-hydroxybutyric acid