257955-49-0Relevant articles and documents
3-Aryl-[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-ones: Tricyclic heteroaromatic derivatives as a new class of benzodiazepine receptor ligands
Primofiore, Giampaolo,Da Settimo, Federico,Taliani, Sabrina,Marini, Anna Maria,La Motta, Concettina,Novellino, Ettore,Greco, Giovanni,Gesi, Marco,Trincavelli, Letizia,Martini, Claudia
, p. 96 - 102 (2007/10/03)
A series of 3-substituted [1,2,4]triazino[4,3-c]benzimidazoles V were prepared and tested at the central benzodiazepine receptor (BzR). These compounds were designed as rigid analogues of the previously described N- benzylindolylglyoxylylamide derivatives IV. The title compounds V showed an affinity which depended directly on the presence of the N(10)-H group and an aromatic ring at position 3. Some of them elicited a 2- or 3-fold higher affinity with respect to that 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 proved to be effective in antagonizing pentylenetetrazole-induced seizures in mice. Attempts were made to interpret the structure-affinity relationships of compounds V in the light of possible tautomeric equilibria involving the ligands.