7254-19-5Relevant articles and documents
Synthesis, structure-activity relationship and antiviral activity of indole-containing inhibitors of Flavivirus NS2B-NS3 protease
Kneubehl, Alexander R.,Li, Xin,Lin, Yi-Lun,Nie, Shenyou,Rico-Hesse, Rebecca,Song, Yongcheng,Vogt, Megan B.,Wu, Fangrui,Wu, Xiaowei,Yao, Yuan,Zhao, Jidong
, (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.
Substituted indole - 2 - formic acid (by machine translation)
-
, (2017/10/28)
This invention relates to a substituted indole - 2 - carboxylic acid synthesis method, is to replace the phenyl hydrazine hydrochloride or arylhydrazines as raw materials, through with pyruvic acid ethyl ester cheng zong, Fischer indole synthesis by reaction of substituted indole - 2 - carboxylic acid ethyl ester, hydrolysis to obtain the substituted - 2 - carboxylic acid. Product purity is greater than 97%, the reaction yield is 64%. Synthesis method of the invention with non-harsh conditions, the operation is simple, and environmental friendliness, it has certain economic benefits. It is a kind of raw materials are easy, simple operation, three wastes, high yield of indole - 2 - carboxylic acid synthesis method. (by machine translation)
New arylthioindoles and related bioisosteres at the sulfur bridging group. 4. Synthesis, tubulin polymerization, cell growth inhibition, and molecular modeling studies
La Regina, Giuseppe,Sarkar, Taradas,Bai, Ruoli,Edler, Michael C.,Saletti, Roberto,Coluccia, Antonio,Piscitelli, Francesco,Minelli, Lara,Gatti, Valerio,Mazzoccoli, Carmela,Palermo, Vanessa,Mazzoni, Cristina,Falcone, Claudio,Scovassi, Anna Ivana,Giansanti, Vincenzo,Campiglia, Pietro,Porta, Amalia,Maresca, Bruno,Hamel, Ernest,Brancale, Andrea,Novellino, Ettore,Silvestri, Romano
experimental part, p. 7512 - 7527 (2010/05/18)
New arylthioindoles along with the corresponding ketone and methylene compounds were potent tubulin assembly inhibitors. As growth inhibitors of MCF-7 cells, sulfur derivatives were superior or sometimes equivalent to the ketones, while methylene derivatives were substantially less effective. Esters 24, 27-29, 36, 39, and 41 showed ～50% of inhibition on human HeLa and HCT116/chr3 cells at 0.5 μM, and these compounds inhibited the growth of HEK, M14, and U937 cells with IC50's in the 78-220 nM range. While murine macrophage J744.1 cell growth was significantly less affected (20% at higher concentrations), four other nontransformed cell lines remained sensitive to these esters. The effect of drug treatment on cell morphology was examined by time-lapse microscopy. In a protocol set up to evaluate toxicity on the Saccharomyces cerevisiae BY4741 wild type strain, compounds 24 and 54 strongly reduced cell growth, and 29, 36, and 39 also showed significant inhibition. 2009 American Chemical Society.
