857809-64-4Relevant 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.
Tanjungides a and B: New antitumoral bromoindole derived compounds from Diazona cf formosa. isolation and total synthesis
Murcia, Carmen,Coello, Laura,Fernandez, Rogelio,Martin, Maria Jesus,Reyes, Fernando,Francesch, Andres,Munt, Simon,Cuevas, Carmen
, p. 1116 - 1130 (2014/03/21)
Tanjungides A (1) (Z isomer) and B (2) (E isomer), two novel dibrominated indole enamides, have been isolated from the tunicate Diazona cf formosa. Their structures were determined by spectroscopic methods including HRMS, and extensive 1D and 2D NMR. The stereochemistry of the cyclised cystine present in both compounds was determined by Marfey's analysis after chemical degradation and hydrolysis. We also report the first total synthesis of these compounds using methyl 1H-indole-3-carboxylate as starting material and a linear sequence of 11 chemical steps. Tanjungides A and B exhibit significant cytotoxicity against human tumor cell lines.
