16732-65-3Relevant academic research and scientific papers
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.
Synthesis, and evaluation of in vitro and in vivo anticancer activity of 14-substituted oridonin analogs: A novel and potent cell cycle arrest and apoptosis inducer through the p53-MDM2 pathway
Shen, Qing-Kun,Deng, Hao,Wang, Shi-Ben,Tian, Yu-Shun,Quan, Zhen-Shan
, p. 15 - 31 (2019/04/10)
A series of novel oridonin derivatives bearing various substituents on the 14-OH position were designed and synthesised. Their antitumour activity was evaluated in vitro against three human cancer cell lines (HCT116, BEL7402, and MCF7). Most tested derivatives showed improved anti-proliferative activity compared to the lead compound oridonin and the positive control drug 5-fluorouracil (5-Fu). Among them, compound C7 (IC50 = 0.16 μM) exhibited the most potent anti-proliferative activity against HCT116 cells; it was about 43- and 155-fold more efficacious than that of oridonin (IC50 = 6.84 μM) and 5-Fu (IC50 = 24.80 μM) in HCT116 cancer cells. Interestingly, the IC50 value of compound C7 in L02 normal cells was 23.6-fold higher than that in HCT116 cells; it exhibited better selective anti-proliferative activity and specificity than oridonin and 5-Fu. Furthermore, compound C7 possibly induced cell cycle arrest and apoptosis by regulating the p53-MDM2 signalling pathway. Notably, C7 displayed more significant suppression of tumour growth than oridonin in colon tumour xenograft models where the tumour growth inhibition rate was 85.82%. Therefore, compound C7 could be a potential lead compound for the development of a novel antitumour agent.
INHIBITORS OF THE MENIN-MLL INTERACTION
-
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.
The first potent and selective non-imidazole human histamine H4 receptor antagonists
Jablonowski, Jill A.,Grice, Cheryl A.,Chai, Wenying,Dvorak, Curt A.,Venable, Jennifer D.,Kwok, Annette K.,Ly, Kiev S.,Wei, Jianmei,Baker, Sherry M.,Desai, Pragnya J.,Jiang, Wen,Wilson, Sandy J.,Thurmond, Robin L.,Karlsson, Lars,Edwards, James P.,Lovenberg, Timothy W.,Carruthers, Nicholas I.
, p. 3957 - 3960 (2007/10/03)
Following the discovery of the human histamine H4 receptor, a high throughput screen of our corporate compound collection identified compound 6 as a potential lead. Investigation of the SAR resulted in the discovery of novel compounds 10e and 10l, which are the first potent and selective histamine H4 receptor antagonists to be described.
