[Zurück]

B. Vega Alanis, D. Siebert, X. Simeone, K. Bampali, L. Wimmer, M. Ernst, M.D. Mihovilovic:
"Selectivity Of Pyrazoloquinolinone Derivatives Towards The Alpha+/beta- Interface Of The Gabaa Receptor";
Poster: XXV EFMC International Symposium on Medicinal Chemistry, Ljubljana; 07.09.2014 - 11.09.2014.

GABAA receptors are the major inhibitory neurotransmitter receptors in the central nervous system. These GABA-gated chloride channels are composed of five subunits that can belong to different subunit classes. Several pyrazoloquinolinone ligands have already been described as high affinity ligands of the benzodiazepine (Bz) binding site but also, they exert a positive modulatory effect at the alpha+beta- interfaces.1,2 Previously, it
was shown that some pyrazoloquinolinone derivatives showed preference towards beta1 containing receptors in terms of potency. Further studies in homology models and mutant receptors confirm that the amino acid located in position 41 of segment G in the beta1 and beta3 subunits strongly influences the potency and efficacy of the tested ligands.3 In the present study, further pyrazoloquinolinone derivatives were studied and results showed
that they possess improved functional selectivity. The results of this study are herein presented and the properties of these compounds will be further investigated.