400744-83-4Relevant articles and documents
Design, synthesis and biological evaluation of novel oseltamivir derivatives as potent neuraminidase inhibitors
Wang, Zhen,Cheng, Li Ping,Zhang, Xing Hua,Pang, Wan,Li, Liang,Zhao, Jin Long
, p. 5429 - 5435 (2017)
Neuraminidase (NA) is one of the particular potential targets for novel antiviral therapy. In this work, a series of neuraminidase inhibitors with the cyclohexene scaffold were studied based upon the combination of 3D-QSAR, molecular docking, and molecular dynamics techniques. The results indicate that the built 3D-QSAR models yield reliable statistical information: the correlation coefficient (r2) and cross-validation coefficient (q2) of CoMFA (comparative molecular field analysis) are 0.992 and 0.819; the r2 and q2 of CoMSIA (comparative molecular similarity analysis) are 0.992 and 0.863, respectively. Molecular docking and MD simulations were conducted to confirm the detailed binding mode of enzyme-inhibitor system. The new NA inhibitors had been designed, synthesized, and their inhibitory activities against group-1 neuraminidase were determined. One agent displayed excellent neuraminidase inhibition, with IC50 value of 39.6 μM against NA, while IC50 value for oseltamivir is 61.1 μM. This compound may be further investigated for the treatment of infection by the new type influenza virus.
Gold Catalysts Can Generate Nitrone Intermediates from a Nitrosoarene/Alkene Mixture, Enabling Two Distinct Catalytic Reactions: A Nitroso-Activated Cycloheptatriene/Benzylidene Rearrangement
Cheng, Mu-Jeng,Kardile, Rahul Dadabhau,Kuo, Tung-Chun,Liu, Rai-Shung,More, Sayaji Arjun
supporting information, p. 5506 - 5511 (2021/07/31)
Gold-catalyzed reactions of cycloheptatrienes with nitrosoarenes yield nitrone derivatives efficiently. This reaction sequence enables us to develop gold-catalyzed aerobic oxidations of cycloheptatrienes to afford benzaldehyde derivatives using CuCl and nitrosoarenes as co-catalysts (10-30 mol %). Our density functional theory calculations support a novel nitroso-activated rearrangement, tropylium → benzylidene. With the same nitrosoarenes, we developed their gold-catalyzed [2 + 2 + 1]-annulations between nitrosobenzene and two enol ethers to yield 5-alkoxyisoxazolidines using 1,4-cyclohexadienes as hydrogen donors.
The Discovery of Novel ACA Derivatives as Specific TRPM2 Inhibitors that Reduce Ischemic Injury Both in Vitro and in Vivo
Zhang, Han,Yu, Peilin,Lin, Hongwei,Jin, Zefang,Zhao, Siqi,Zhang, Yi,Xu, Qingxia,Jin, Hongwei,Liu, Zhenming,Yang, Wei,Zhang, Liangren
, p. 3976 - 3996 (2021/05/04)
The transient receptor potential melastatin 2 (TRPM2) channel is associated with ischemia/reperfusion injury, inflammation, cancer, and neurodegenerative diseases. However, the limit of specific inhibitors impedes the development of TRPM2-targeted therapeutic agents. To discover more potent and selective TRPM2 inhibitors, 59 N-(p-amylcinnamoyl) anthranilic acid (ACA) derivatives were synthesized and evaluated using calcium imaging and electrophysiology approaches. Systematic structure-activity relationship studies resulted in some potent compounds inhibiting the TRPM2 channel with sub-micromolar half-maximal inhibitory concentration values. Among them, the preferred compound A23 exhibited TRPM2 selectivity over TRPM8 and TRPV1 channels as well as phospholipase A2 and showed neuroprotective activity in vitro. Following pharmacokinetic studies, A23 was further evaluated in a transient middle cerebral artery occlusion model in vivo, which significantly reduced cerebral infarction. These data indicate that A23 might serve as a useful tool for TRPM2-related research as well as a lead compound for the development of therapeutic agents for ischemic injury.