Document Report Card

ID: ALA1138062

Journal: J Med Chem

Title: Hydroxy-1,2,5-oxadiazolyl moiety as bioisoster of the carboxy function. Synthesis, ionization constants, and pharmacological characterization of gamma-aminobutyric acid (GABA) related compounds.

Authors: Lolli ML, Hansen SL, Rolando B, Nielsen B, Wellendorph P, Madsen K, Larsen OM, Kristiansen U, Fruttero R, Gasco A, Johansen TN.

Abstract: Three 4-substituted 1,2,5-oxadiazol-3-ols containing aminoalkyl substituents (analogues and homologues of gamma-aminobutyric acid (GABA)) were synthesized to investigate the hydroxy-1,2,5-oxadiazolyl moiety as a bioisoster for a carboxyl group at GABA receptors. The pK(a) values of the target compounds were close to those of GABA. At GABA(A) receptors of cultured cerebral cortical neurons, weak agonist and partial agonist profiles were identified, demonstrating the 4-hydroxy-1,2,5-oxadiazol-3-yl unit to be a nonclassical carboxyl group bioisoster.

CiteXplore: 16821803

DOI: 10.1021/jm051288b