Analogs of .gamma.-hydroxybutyric acid. Synthesis and binding studies

摘要: Substituted 4-hydroxybutyric (GHB) or trans-4-hydroxycrotonic acids (T-HCA) and structurally related compounds were synthesized submitted to [3H]GHB binding. Structure-activity relationships studies highlighted for binding (a) the necessity of a nonlactonic, relatively extended conformation gamma-hydroxybutyric chain, (b) existence some bulk tolerance in vicinity hydroxyl group, (c) high sensitivity toward isosteric replacements carboxyl groups. T-HCA has been recently identified as naturally occurring substance central nervous system (CNS) shows better affinity than GHB. Our findings are favor presence CNS specific GHB sites, which different from GABA picrotoxin may be an endogenous ligand.