Synthesis of new N-benzylpiperidine derivatives as cholinesterase inhibitors with 閻?amyloid anti-aggregation properties and beneficial effects on memory in vivo was written by Wieckowska, Anna;Wieckowski, Krzysztof;Bajda, Marek;Brus, Boris;Salat, Kinga;Czerwinska, Paulina;Gobec, Stanislav;Filipek, Barbara;Malawska, Barbara. And the article was included in Bioorganic & Medicinal Chemistry in 2015.Reference of 954-81-4 This article mentions the following:
Due to the complex nature of Alzheimer’s disease, multi-target-directed ligand approaches are one of the most promising strategies in the search for effective treatments. Acetylcholinesterase, butyrylcholinesterase and 閻?amyloid are the predominant biol. targets in the search for new anti-Alzheimer’s agents. Our aim was to combine both anticholinesterase and 閻?amyloid anti-aggregation activities in one mol., and to determine the therapeutic potential in vivo. We designed and synthesized 28 new compounds as derivatives of donepezil that contain the N-benzylpiperidine moiety combined with the phthalimide or indole moieties. Most of these test compounds showed micromolar activities against cholinesterases and aggregation of 閻?amyloid, combined with pos. results in blood-brain barrier permeability assays. The most promising compound 23 (2-(8-(1-(3-chlorobenzyl)piperidin-4-ylamino)octyl)isoindoline-1,3-dione) is an inhibitor of butyrylcholinesterase (IC50 = 0.72 婵炴挾鎷? that has 閻?amyloid anti-aggregation activity (72.5% inhibition at 10 婵炴挾鎷? and can cross the blood-brain barrier. Moreover, in an animal model of memory impairment induced by scopolamine, the activity of 23 was comparable to that of donepezil. The selected compound 23 is an excellent lead structure in the further search for new anti-Alzheimer’s agents. In the experiment, the researchers used many compounds, for example, N-(5-Bromopentyl)phthalimide (cas: 954-81-4Reference of 954-81-4).
N-(5-Bromopentyl)phthalimide (cas: 954-81-4) belongs to organobromine compounds. Many of the organo bromine compounds are relatively nonpolar. Bromine is more electronegative than carbon (2.8 vs 2.5) and hence the carbon in a carbon闁艰京鐗梤omine bond is electrophilic in nature. The reactivity of organobromine compounds resembles but is intermediate between the reactivity of organochlorine and organoiodine compounds. For many applications, organobromides represent a compromise of reactivity and cost.Reference of 954-81-4
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary