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.

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 PASSETTI, FEDERICO;TALIANI, SABRINA;MARINI, ANNA MARIA;LA MOTTA, CONCETTINA;GESI, MARCO;TRINCAVELLI, MARIA LETIZIA;MARTINI, CLAUDIA
2000

Abstract

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.
Primofiore, Giampaolo; DA SETTIMO PASSETTI, Federico; Taliani, Sabrina; Marini, ANNA MARIA; LA MOTTA, Concettina; Novellino, E.; Greco, G.; Gesi, Marco; Trincavelli, MARIA LETIZIA; Martini, Claudia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/203722
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