29481-31-0Relevant academic research and scientific papers
Discovery of Highly Potent Pinanamine-Based Inhibitors against Amantadine- and Oseltamivir-Resistant Influenza A Viruses
Zhao, Xin,Li, Runfeng,Zhou, Yang,Xiao, Mengjie,Ma, Chunlong,Yang, Zhongjin,Zeng, Shaogao,Du, Qiuling,Yang, Chunguang,Jiang, Haiming,Hu, Yanmei,Wang, Kefeng,Mok, Chris Ka Pun,Sun, Ping,Dong, Jianghong,Cui, Wei,Wang, Jun,Tu, Yaoquan,Yang, Zifeng,Hu, Wenhui
, p. 5187 - 5198 (2018)
Influenza pandemic is a constant major threat to public health caused by influenza A viruses (IAVs). IAVs are subcategorized by the surface proteins hemagglutinin (HA) and neuraminidase (NA), in which they are both essential targets for drug discovery. While it is of great concern that NA inhibitor oseltamivir resistant strains are frequently identified from human or avian influenza virus, structural and functional characterization of influenza HA has raised hopes for new antiviral therapies. In this study, we explored a structure-activity relationship (SAR) of pinanamine-based antivirals and discovered a potent inhibitor M090 against amantadine-resistant viruses, including the 2009 H1N1 pandemic strains, and oseltamivir-resistant viruses. Mechanism of action studies, particularly hemolysis inhibition, indicated that M090 targets influenza HA and it occupied a highly conserved pocket of the HA2 domain and inhibited virus-mediated membrane fusion by locking the bending state of HA2 during the conformational rearrangement process. This work provides new binding sites within the HA protein and indicates that this pocket may be a promising target for broad-spectrum anti-influenza A drug design and development.
Cyclopropyl thiophene methylamine compound or pharmaceutically acceptable salt thereof and application of cyclopropyl thiophene methylamine compound
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Paragraph 0075-0078, (2021/03/10)
The invention belongs to the technical field of medicines, and discloses a cyclopropyl thiophene methylamine compound or pharmaceutically acceptable salt and application thereof. The invention relatesto the cyclopropyl thiophene methylamine compound with a structure shown in a formula (I) or the pharmaceutically acceptable salt or a stereoisomer or a prodrug molecule thereof, wherein R1 is selected from hydrogen, cyano, alkyl, aryl, heteroaryl, alkanoyl, sulfonyl, aryl heterocyclic group or heteroaryl heterocyclic group, R2 is selected from hydrogen, halogen, cyano, alkyl, aryl, heteroaryl, alkanoyl, carboxyl, aminoacyl, amido, amidino, guanidino, guanidino, hydroxyl, alkoxy, aryloxy, ester group, sulfydryl, sulfonyl, aryl heterocyclic group or heteroaryl heterocyclic group, and A is an alkane group or a heterocyclic alkyl group with a three-dimensional cage-shaped structure. The cyclopropyl thiophene methylamine compound or the pharmaceutically acceptable salt thereof has high activity to variant influenza viruses and drug-resistant viruses and low toxicity to human bodies.
