1095985-13-9Relevant academic research and scientific papers
Discovery of highly potent and selective influenza virus neuraminidase inhibitors targeting 150-cavity
Jia, Ruifang,Zhang, Jian,Bertagnin, Chiara,Cherukupalli, Srinivasulu,Ai, Wei,Ding, Xiao,Li, Zhuo,Zhang, Jiwei,Ju, Han,Ma, Xiuli,Loregian, Arianna,Huang, Bing,Zhan, Peng,Liu, Xinyong
, (2021/01/05)
Encouraged by our earlier discovery of N1-selective inhibitors, the 150-cavity of influenza virus neuraminidases (NAs) could be further exploited to yield more potent oseltamivir derivatives. Herein, we report the design, synthesis and biological evaluation of a series of novel oseltamivir derivatives via the structural modifications at C5–NH2 of oseltamivir targeting 150-cavity. Among them, compound 5c bearing 4-(3-methoxybenzyloxy)benzyl group exhibited the most potent activity, which was lower or modestly improved activities than oseltamivir carboxylate (OSC) against N1 (H1N1), N1 (H5N1) and N1 (H5N1–H274Y). Specifically, there was 30-fold loss of activity against the wild-type strain H1N1. However, 5c displayed 4.85-fold more potent activity than OSC against H5N1–H274Y NA. Also, 5c demonstrated low cytotoxicity in vitro and no acute toxicity in mice. Molecular docking studies provided insights into the high potency of 5c against N1 and N1–H274Y mutant NAs. Besides, the in silico prediction of physicochemical properties and CYP enzymatic inhibitory ability of representative compounds were conducted to evaluate their drug-like properties.
Substituted pyridino imidazole compound and application thereof in preparation of drugs for treating malignant tumor diseases
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Paragraph 0064-0066, (2020/08/18)
The invention belongs to the field of medicines, and discloses a substituted pyridino imidazole compound as shown in the specification and an application thereof in preparation of a medicine for treating lung cancer. Cell level experiments prove that the compound can inhibit proliferation, migration, invasion and clone formation of lung cancer cells, induce apoptosis of the lung cancer cells and inhibit the phosphorylation level of STAT3; mouse in-vivo experiments show that the compound can inhibit growth and metastasis of lung cancer cells, specifically inhibit an STAT3 signal path, inhibit growth of lung cancer cell transplantation tumors and patient PDX tumors in an animal model, lay a foundation for subsequent new drug research and development, and have important theoretical significance and wide application prospects.
