Wan, Lin-Xi; Zhen, Yong-Qi; He, Zhen-Xiang; Zhang, Yang; Zhang, Lan; Li, Xiaohuan; Gao, Feng; Zhou, Xian-Li published the artcile< Late-Stage Modification of Medicine: Pd-Catalyzed Direct Synthesis and Biological Evaluation of N-Aryltacrine Derivatives>, Application In Synthesis of 401-78-5, the main research area is tacrine aryl preparation Buchwald Hartwig cross coupling palladium catalyst; cholinesterase inhibitor aryltacrine; hepatotoxicity aryltacrine; neuroprotective aryltacrine; mol docking methoxypyridinyl tacrine acetylcholinesterase butyrylcholinesterase; blood brain barrier permeability aryltacrine.
A new series of N-aryltacrine derivatives was designed and synthesized as cholinesterase inhibitors by the late-stage modification of tacrine, using the palladium-catalyzed Buchwald-Hartwig cross-coupling reaction. In vitro inhibition assay against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) demonstrated that most of the synthesized compounds had potent AChE inhibitory activity with neg. inhibition of BuChE. Among them, N-(4-(trifluoromethyl)phenyl)-tacrine (I) and N-(4-methoxypyridin-2-yl)-tacrine (II) showed the most potent activity against AChE (IC50 values of 1.77 and 1.48μM, resp.). The anti-AChE activity of I and II was 3.5 times more than that of tacrine (IC50 value of 5.16μM). Compound II also displayed anti-BuChE activity with an IC50 value of 19.00μM. Cell-based assays against HepG2 and SH-SY5Y cell lines revealed that II had significantly lower hepatotoxicity compared to tacrine, with addnl. neuroprotective activity against H2O2-induced damage in SH-SY5Y cells. The advantages including synthetic accessibility, high potency, low toxicity, and adjunctive neuroprotective activity make compound II a new promising multifunctional candidate for the treatment of Alzheimer’s disease.
ACS Omega published new progress about Alzheimer disease. 401-78-5 belongs to class bromides-buliding-blocks, and the molecular formula is C7H4BrF3, Application In Synthesis of 401-78-5.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary