| Abstract
| - Novel N-substituted indol-3-ylglyoxylamides (10−37) were synthesized and evaluated as ligands of thebenzodiazepine receptor (BzR). In an effort to achieve affinity-based selectivity among BzR subtypes, thesecompounds were designed to probe the LDi and L2 lipophilic regions. Taking the α1-selective benzylindolylglyoxylamides Ia and Ib as leads, we varied the substituent on the benzylamide phenyl ring (compounds10−23) or replaced the benzyl moiety with alkyl groups (compounds 24−37). The above structural changesgave no shift of selectivity from the α1 toward the α2 or α5 subtypes, thus confirming that a ligand whichoccupies the LDi region probably exhibits α1 selectivity, despite its interactions with other lipophilic areasin the receptor binding cleft. Compound 11 (N-(p-methylbenzyl)-5-nitroindol-3-ylglyoxylamide), whichselectively binds with a full agonist efficacy at the α1 receptor subtype and displays sedative action, can beregarded as an interesting potential zolpidem-like sedative−hypnotic agent.
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