1191921-01-3Relevant articles and documents
The hydrophobic side chain of oseltamivir influences type A subtype selectivity of neuraminidase inhibitors
Lin, Xiong,Qin-Hua, Chen,Peng, Li,Chun-Lei, Li,Guang-De, Yang
, p. 105 - 115 (2017/10/06)
Neuraminidase, which plays a critical role in the influenza virus life cycle, is a target for new therapeutic agents. The study of structure–activity relationships revealed that the C-5 position amino group of oseltamivir was pointed to 150-cavity of the neuraminidase in group 1. This cavity is important for selectivity of inhibitors against N1 versus N2 NA. A serial of influenza neuraminidase inhibitors with the oseltamivir scaffold containing lipophilic side chains at the C-5 position have been synthesized and evaluated for their influenza neuraminidase inhibitory activity and selectivity. The results indicated that compound 13o (H5N1 IC50?=?0.1?±?0.04?μm, H3N2 IC50?=?0.26?±?0.18?μm) showed better inhibitory activity and selectivity against the group 1 neuraminidase. This study may provide a clue to design of better group 1 neuraminidase inhibitors.
Acyl neuraminidase inhibitor and medical application thereof
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Paragraph 0031; 0032; 0033, (2017/07/21)
The invention relates to the field of medicinal chemistry, in particular to an oseltamivir primary amine acylated derivative, as well as a preparation method and medical application of the oseltamivir primary amine acylated derivative. The oseltamivir primary amine acylated derivative is mainly medically applied to a series of infectious diseases caused by influenza viruses. Particularly, the invention provides a derivative as shown in the general formula (I), as well as pharmaceutically acceptable salt and an isomer of the derivative. R1 and R2 are as described in claims and the specification.
Synthesis and biological evaluation of NH2-acyl oseltamivir analogues as potent neuraminidase inhibitors
Wang, Kuanglei,Yang, Fei,Wang, Lihui,Liu, Kemin,Sun, Lu,Lin, Bin,Hu, Yaping,Wang, Boyu,Cheng, Maosheng,Tian, Yongshou
, p. 648 - 656 (2017/10/31)
Neuraminidase inhibitors can deter nascent viruses from infecting intact cells by preventing their release from host cells. Herein, a neuraminidase inhibitor 11b absent of basic moieties was discovered in the process of searching for inhibitors targeting 150 cavity. It exhibited potent inhibitions against wild-type neuraminidases from group 1 (H5N1 and H1N1) and group 2 (H7N9) subtypes with IC50 values similar to those of oseltamivir carboxylate. Moreover, 11b showed moderate inhibitions against mutant neuraminidases from H5N1-H274Y and H1N1-H274Y with IC50 values of 2075 nM and 1382 nM, which were inferior to those of oseltamivir carboxylate (6095 nM and 4071 nM). The results were not consistent with the recognized SARs that a basic moiety was an indispensable part of a potent inhibitor.
