a-867744 and Amnesia

a-867744 has been researched along with Amnesia* in 1 studies

*Amnesia: Pathologic partial or complete loss of the ability to recall past experiences (AMNESIA, RETROGRADE) or to form new memories (AMNESIA, ANTEROGRADE). This condition may be of organic or psychologic origin. Organic forms of amnesia are usually associated wit [MeSH]

Other Studies

1 other study(ies) available for a-867744 and Amnesia

Article	Year
Discovery of novel positive allosteric modulators of the α7 nicotinic acetylcholine receptor: Scaffold hopping approach. European journal of medicinal chemistry, 2021, Mar-15, Volume: 214 The paper focuses on the scaffold hopping-based discovery and characterization of novel nicotinic alpha 7 receptor positive modulator (α7 nAChR PAM) ligands around the reference molecule (A-867744). First, substantial efforts were carried out to assess the importance of the various pharmacophoric elements on the in vitro potency (SAR evaluation) by chemical modifications. Subsequently, several new derivatives with versatile, heteroaromatic central cores were synthesized and characterized. A promising, pyrazole-containing new chemotype with good physicochemical and in vitro parameters was identified. Retrospective analysis based on homology modeling was also carried out. Besides its favorable in vitro characteristics, the most advanced derivative 69 also showed in vivo efficacy in a rodent model of cognition (scopolamine-induced amnesia in the mouse place recognition test) and acceptable pharmacokinetic properties. Based on the in vivo data, the resulting molecule with advanced drug-like characteristics has the possibility to improve cognitive performance in a biologically relevant dose range, further strengthening the view of the supportive role of α7 nACh receptors in the cognitive processes. Topics: Administration, Oral; Allosteric Regulation; alpha7 Nicotinic Acetylcholine Receptor; Amnesia; Animals; Dose-Response Relationship, Drug; Drug Discovery; HEK293 Cells; Humans; Male; Maze Learning; Mice; Microsomes, Liver; Molecular Structure; Nicotinic Agonists; Pyrazoles; Rats; Rats, Wistar; Scopolamine; Structure-Activity Relationship	2021

Article

Year

Discovery of novel positive allosteric modulators of the α7 nicotinic acetylcholine receptor: Scaffold hopping approach.

European journal of medicinal chemistry, 2021, Mar-15, Volume: 214

The paper focuses on the scaffold hopping-based discovery and characterization of novel nicotinic alpha 7 receptor positive modulator (α7 nAChR PAM) ligands around the reference molecule (A-867744). First, substantial efforts were carried out to assess the importance of the various pharmacophoric elements on the in vitro potency (SAR evaluation) by chemical modifications. Subsequently, several new derivatives with versatile, heteroaromatic central cores were synthesized and characterized. A promising, pyrazole-containing new chemotype with good physicochemical and in vitro parameters was identified. Retrospective analysis based on homology modeling was also carried out. Besides its favorable in vitro characteristics, the most advanced derivative 69 also showed in vivo efficacy in a rodent model of cognition (scopolamine-induced amnesia in the mouse place recognition test) and acceptable pharmacokinetic properties. Based on the in vivo data, the resulting molecule with advanced drug-like characteristics has the possibility to improve cognitive performance in a biologically relevant dose range, further strengthening the view of the supportive role of α7 nACh receptors in the cognitive processes.

Topics: Administration, Oral; Allosteric Regulation; alpha7 Nicotinic Acetylcholine Receptor; Amnesia; Animals; Dose-Response Relationship, Drug; Drug Discovery; HEK293 Cells; Humans; Male; Maze Learning; Mice; Microsomes, Liver; Molecular Structure; Nicotinic Agonists; Pyrazoles; Rats; Rats, Wistar; Scopolamine; Structure-Activity Relationship

2021