54477-05-3Relevant academic research and scientific papers
Synthesis, biological evaluation and molecular modeling of benzofuran piperidine derivatives as Aβ antiaggregant
Chowdhury, Sharmin Reza,Gu, Jinxin,Hu, Yixin,Wang, Juntao,Lei, Shuwen,Tavallaie, Mojdeh S.,Lam, Celine,Lu, Dan,Jiang, Faqin,Fu, Lei
, (2021/06/15)
A series of benzofuran piperidine derivatives were designed, synthesized and evaluated as multifunctional Aβ antiaggregant to treat Alzheimer's disease (AD). In vitro results revealed that all of them are very good Aβ antiaggregants and some of the compounds are potent acetylcholinesterase (AChE) inhibitors with moderate antioxidant property. Selected compounds were also tested for neuroprotection activity, LDH release, ATP production and inhibitory activity to prevent Aβ peptides binding to the cell membrane. The different modifications introduced in the structure of our lead compound 3 (hAChE IC50 = 61 μM and self induced Aβ 25-35 aggregation 45.45%), to increase its activity toward AD related targets. The most interesting multifunctional Aβ antiaggregants were compounds 3a, 3h and 3i, highlighting 3h as potent Aβ antiaggregant and good antiacetylholinesterase inhibitor (self induced Aβ 25-35 aggregation 57.71% and hAChE IC50 = 21 μM), with good neuroprotective and antioxidant activity. In addition, these three most promising compounds prevent intracellular reactive oxygen species (ROS) formation and cell apoptosis induced by Aβ25-35 peptides in SH-SY5Y cells. Molecular docking studies were also accomplished to understand the binding interaction of these compounds on Aβ monomer, Aβ fibril and AChE. Based on all data, compounds 3a, 3h and 3i were concluded as potent multifunctional Aβ antiaggregant, useful candidate for the treatment of AD.
Synthesis and structure-activity relationship of dihydrobenzofuran derivatives as novel human GPR119 agonists
Ye, Xiang-Yang,Morales, Christian L.,Wang, Ying,Rossi, Karen A.,Malmstrom, Sarah E.,Abousleiman, Mojgan,Sereda, Larisa,Apedo, Atsu,Robl, Jeffrey A.,Miller, Keith J.,Krupinski, John,Wacker, Dean A.
, p. 2539 - 2545 (2014/05/20)
Through appropriate medicinal chemistry design tactics and computer-assisted conformational modeling, the initial lead A was evolved into a series of dihydrobenzofuran derivatives 3 as potent GPR119 agonists. This Letter describes the optimization of general structure 3, including the substituent(s) on dihydrobenzofuran, the R1 attachment on right-hand piperidine nitrogen, and the left-hand piperidine/piperazine and its attachment R2. The efforts led to the identification of compounds 13c and 24 as potent human GPR119 modulators with favorable metabolic stability, ion channel activity, and PXR profiles.
