The synthesis and the binding study of new 3-iodiopyrazolo[5,1-c][1,2,4] benzotriazine 5-oxides 8-alkyloxy substituted are reported. The replacement at position 3 with an iodine atom, with respect to substituents capable to form a three centered hydrogen bond and/or to form pi-pi stacking interaction with receptor protein, gave high affinity ligands, independently of the 8-alkyloxy substituent. High-affinity ligands were studied in mice in vivo for their pharmacological effects, considering five potential benzodiazepine actions: anxiolytic-like effects, motor coordination, anticonvulsant action, mouse learning and memory impairment, and ethanol-potentiating action. Compounds 5c and 5'c have an inverse agonist profile and for the first time is evidenced a pro-mnemonic activity. These compounds were evaluated also for their binding at Benzodiazepine site on GABA(A) receptor complex (GABA(A)/BzR complex) subtype to evaluate their subtype selectivity.
|Autori interni:||MARTINI, CLAUDIA|
|Autori:||GUERRINI GABRIELLA; CICIANI GIOVANNA; CAMBI GIOVANNI; BRUNI FABRIZIO; SELLERI SILVIA; BESNARD FRANOIS; MONTALI MARINA; MARTINI C; GHELARDINI CARLA; GALEOTTI NICOLETTA; COSTANZO ANNARELLA|
|Titolo:||Novel 3-iodo-8-ethoxypyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide as promising lead for design of alpha5-inverse agonist useful tools for therapy of mnemonic damage|
|Anno del prodotto:||2007|
|Digital Object Identifier (DOI):||10.1016/j.bmc.2007.01.053|
|Appare nelle tipologie:||1.1 Articolo in rivista|