Novel 3-iodo-8-ethoxypyrazolo[5,1-c][1,2,4]benzotriazine 5-oxide as promising lead for design of α5-inverse agonist useful tools for therapy of mnemonic damage

Novel agonists of benzodiazepine receptors: Design, synthesis, binding assay and pharmacological evaluation of 1,2,4-triazolo[1,5-a]pyrimidinone and 3-amino-1,2,4-triazole derivatives

“…Interaction of the most potent BZD ligand 4c, 3-(2-chlorobenzyl)-5-methyl-2-phenyl- [1,2,4]triazolo[1,5-a]pyrimidin-7(3H)-one,with amino acids of diazepam-binding pocket of GABA A receptor (α1β2ϒ2) and the orientation of this ligand along with estazolam in the BZD-binding site that examined by a flexible docking experiment using AutoDock 4.2.3 software were observed in Figure 3(a, b). It is obvious that the carbonyl group of the 4c was in the same direction of the nitrogen moiety of estazolam for hydrogen binding with α1…”

“…), a BZD with amnestic effects. 1 The passive avoidance cage had two different compartments separated by a sliding door. One compartment was black and dark and another one was white and lighted.…”

“…1 The pharmacological effects of BZDs result from their affinity for a specific binding site on the GABA A receptors, known as the BZD receptor. [2][3][4] BZD receptor agonists modulate the allosteric GABA binding site and increase the opening of a selective chloride ion channel that causes hyperpolarization of the postsynaptic membrane.…”

“…[2][3][4] BZD receptor agonists modulate the allosteric GABA binding site and increase the opening of a selective chloride ion channel that causes hyperpolarization of the postsynaptic membrane. 1 Since BZDs have some adverse effects, 5 development of the novel BZD receptor agonists is still continued and a great deal of attention. Among all pharmacophores proposed for binding to the BZD receptors, an aromatic ring and a coplanar proton-accepting group in suitable distance are essential for interaction with the receptor.…”

Novel 4-thiazolidinone derivatives as agonists of benzodiazepine receptors: design, synthesis and pharmacological evaluation

“…al., 2006[10]), which are the greatest population of brain inhibitory neurotransmitter receptors (Guerrini et. al., 2007[9]). The GABA A receptors are symmetric heteropentamers that are made of different subunits “(α1-6, β1-3, γ1-3, δ, ε, θ, π and ρ1-3) with an integral channel that is permeable to chloride ions” (Rudolph and Knoflach, 2011[16]).…”