98760-08-8Relevant articles and documents
Coupled fermentation-bioconversion process for production of chiral α-chlorohydrin with recombinant ketoreductase
Yang, Zhongyi,Li, Xin,Cai, Ganghua,Peng, Chunlong,Zhong, Yongjun,Luo, Xi
, p. 34 - 39 (2019)
Enzymatic production of chemicals typically includes fermentation of engineered bacteria, preparation of enzymes, and bioconversion processes. Here coupled fermentation-bioconversion process for production of chiral atazanavir intermediate α-chlorohydrin
Peptidomimetic plasmepsin inhibitors with potent anti-malarial activity and selectivity against cathepsin D
Zogota, Rimants,Kinena, Linda,Withers-Martinez, Chrislaine,Blackman, Michael J.,Bobrovs, Raitis,Pantelejevs, Teodors,Kanepe-Lapsa, Iveta,Ozola, Vita,Jaudzems, Kristaps,Suna, Edgars,Jirgensons, Aigars
supporting information, p. 344 - 352 (2018/12/11)
Following up the open initiative of anti-malarial drug discovery, a GlaxoSmithKline (GSK) phenotypic screening hit was developed to generate hydroxyethylamine based plasmepsin (Plm) inhibitors exhibiting growth inhibition of the malaria parasite Plasmodium falciparum at nanomolar concentrations. Lead optimization studies were performed with the aim of improving Plm inhibition selectivity versus the related human aspartic protease cathepsin D (Cat D). Optimization studies were performed using Plm IV as a readily accessible model protein, the inhibition of which correlates with anti-malarial activity. Guided by sequence alignment of Plms and Cat D, selectivity-inducing structural motifs were modified in the S3 and S4 sub-pocket occupying substituents of the hydroxyethylamine inhibitors. This resulted in potent anti-malarials with an up to 50-fold Plm IV/Cat D selectivity factor. More detailed investigation of the mechanism of action of the selected compounds revealed that they inhibit maturation of the P. falciparum subtilisin-like protease SUB1, and also inhibit parasite egress from erythrocytes. Our results indicate that the anti-malarial activity of the compounds is linked to inhibition of the SUB1 maturase plasmepsin subtype Plm X.
A method of preparing intermediates of luck sha neiwei
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Paragraph 0045; 0051; 0058; 0065, (2018/03/26)
The invention provides a preparation method for a fosamprenir intermediate. The preparation method comprises the following steps: taking benzyl cyanide as a raw material, and performing steps of nitrile hydrolysis, acylation, reaction with a Grignard reagent, ammonization, cyclizing and the like for synthesizing (2R,3S)-1,2-epoxy-3-t-butyloxycarborylamino-4-phenyl butane. The method is reasonable in process, simple to operate, low in cost and high in yield; with the method, industrialization can be well realized and the production efficiency is improved.