| Abstract
| - A series of 3-substituted [1,2,4]triazino[4,3-c]benzimidazoles V were prepared and tested atthe central benzodiazepine receptor (BzR). These compounds were designed as rigid analoguesof the previously described N-benzylindolylglyoxylylamide derivatives IV. The title compoundsV showed an affinity which depended directly on the presence of the N(10)-H group and anaromatic ring at position 3. Some of them elicited a 2- or 3-fold higher affinity with respect tothat of the indolylglyoxylylamide derivatives IV (R = H). The GABA ratio and [35S]-tert-butylcyclophosphorothionate binding data revealed an efficacy profile of partial inverse agonists/antagonists for compounds 1c,e,f,j,k, and of a partial agonist for 2c. This last compound provedto be effective in antagonizing pentylenetetrazole-induced seizures in mice. Attempts were madeto interpret the structure−affinity relationships of compounds V in the light of possibletautomeric equilibria involving the ligands.
|
