16732-65-3Relevant articles and documents
Synthesis, structure-activity relationship and antiviral activity of indole-containing inhibitors of Flavivirus NS2B-NS3 protease
Nie, Shenyou,Zhao, Jidong,Wu, Xiaowei,Yao, Yuan,Wu, Fangrui,Lin, Yi-Lun,Li, Xin,Kneubehl, Alexander R.,Vogt, Megan B.,Rico-Hesse, Rebecca,Song, Yongcheng
, (2021/08/26)
Zika virus belongs to the Flavivirus family of RNA viruses, which include other important human pathogens such as dengue and West Nile virus. There are no approved antiviral drugs for these viruses. The highly conserved NS2B-NS3 protease of Flavivirus is essential for the replication of these viruses and it is therefore a drug target. Compound screen followed by medicinal chemistry optimization yielded a novel series of 2,6-disubstituted indole compounds that are potent inhibitors of Zika virus protease (ZVpro) with IC50 values as low as 320 nM. The structure-activity relationships of these and related compounds are discussed. Enzyme kinetics studies show the inhibitor 66 most likely exhibited a non-competitive mode of inhibition. In addition, this series of ZVpro inhibitors also inhibit the NS2B-NS3 protease of dengue and West Nile virus with reduced potencies. The most potent compounds 66 and 67 strongly inhibited Zika virus replication in cells with EC68 values of 1–3 μM. These compounds are novel pharmacological leads for further drug development targeting Zika virus.
INHIBITORS OF THE MENIN-MLL INTERACTION
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Page/Page column 90; 91, (2018/04/14)
The present invention is directed to inhibitors of the interaction of menin with MLL and MLL fusion proteins, pharmaceutical compositions containing the same, and their use in the treatment of cancer and other diseases mediated by the menin-MLL interaction.