496-41-3Relevant articles and documents
Palladium-Catalyzed C?H Functionalization of Phenyl 2-Pyridylsulfonates
Li, Bin,Guo, Dong-Dong,Guo, Shi-Huan,Pan, Gao-Fei,Gao, Ya-Ru,Wang, Yong-Qiang
, p. 130 - 144 (2017)
An efficient palladium(II)-catalyzed intermolecular direct ortho-alkenylation and acetoxylation of phenols has been developed. The reaction proceeded via a seven-membered cyclopalladated intermediate and showed complete regio- and diastereoselectivity. The approach also provided an efficient route for the synthesis of coumarins and benzofurans.
Oxidative Cleavage of β -Keto Sulfones via Nitrous Acid
Abdel-Aziz, Hatem A.
, (2014)
The reaction of nitrous acid with 1-aryl-2-(arylsulfonyl)ethanones 3a-e afforded the unexpected arenecarboxylic acids 12a-e, formic acid 14, and benzene/4-toluenesulfinic acid 15a, b through oxidative cleavage reaction. 4-Chlorobenzoic acid (12a), [1,1′-biphenyl]-4-carboxylic acid (12b), 2-naphthoic acid (12c), 2-thiophenecarboxylic acid (12d), and 2-benzofurancarboxylic acid (12e) were isolated in 72%, 62%, 55%, 58%, and 62% yields, respectively. The reported mechanistic pathways proposed the production of 1-aryl-2-(phenyl/tolylsulfonyl)ethane-1,2-dione 7 instead of arenecarboxylic acids 12. A mechanistic pathway to explain the reaction of nitrous acid with 1-aryl-2-(arylsulfonyl)ethanones 3a-e was suggested. In this pathway, the intermediate 1,2-oxazete 10 lost benzene/4-toluenesulfinic acid 15 to produce 1,2-oxazet-3-one 11. Ring cleavage of the latter intermediate afforded the arenecarboxylic acids 12.
Investigation of the effect of different linker chemotypes on the inhibition of histone deacetylases (HDACs)
Linciano, Pasquale,Benedetti, Rosaria,Pinzi, Luca,Russo, Fabiana,Chianese, Ugo,Sorbi, Claudia,Altucci, Lucia,Rastelli, Giulio,Brasili, Livio,Franchini, Silvia
, (2020/11/24)
Histone Deacetylases (HDACs) are among the most attractive and interesting targets in anticancer drug discovery. The clinical relevance of HDAC inhibitors (HDACIs) is testified by four FDA-approved drugs for cancer treatment. However, one of the main drawbacks of these drugs resides in the lack of selectivity against the different HDAC isoforms, resulting in severe side effects. Thus, the identification of selective HDACIs represents an exciting challenge for medicinal chemists. HDACIs are composed of a cap group, a linker region, and a metal-binding group interacting with the catalytic zinc ion. While the cap group has been extensively investigated, less information is available about the effect of the linker on isoform selectivity. To this aim, in this work, we explored novel linker chemotypes to direct isoform selectivity. A small library of 25 hydroxamic acids with hitherto unexplored linker chemotypes was prepared. In vitro tests demonstrated that, depending on the linker type, some candidates selectively inhibit HDAC1 over HDAC6 isoform or vice versa. Docking calculations were performed to rationalize the effect of the novel linker chemotypes on biologic activity. Moreover, four compounds were able to increase the levels of acetylation of histone H3 or tubulin. These compounds were also assayed in breast cancer MCF7 cells to test their antiproliferative effect. Three compounds showed a significant reduction of cancer proliferation, representing valuable starting points for further optimization.
Synthesis and biological evaluation of novel shikonin-benzo[b]furan derivatives as tubulin polymerization inhibitors targeting the colchicine binding site
Kong, Ling-Yi,Leng, Jia-Fu,Lian, Bao-Ping,Shao, Yu-Ying,Xia, Yuan-Zheng,Yin, Yong
, (2020/02/11)
A novel series of shikonin-benzo[b]furan derivatives were designed and synthesized as tubulin polymerization inhibitors, and their biological activities were evaluated. Most compounds revealed the comparable anti-proliferation activities against the cancer cell lines to that of shikonin and simultaneously low cytotoxicity to non-cancer cells. Among them, compound 6c displayed powerful anti-cancer activity with the IC50 value of 0.18 μM against HT29 cells, which was significantly better than that of the reference drugs shikonin and CA-4. What's more, 6c could inhibit tubulin polymerization and compete with [3H] colchicine in binding to tubulin. Further biological studies depicted that 6c can induce cell apoptosis and cell mitochondria depolarize, regulate the expression of apoptosis related proteins in HT29 cells. Besides, 6c actuated the HT29 cell cycle arrest at G2/M phase, and influenced the expression of the cell-cycle related protein. Moreover, 6c displayed potent inhibition on cell migration and tube formation that contributes to the antiangiogenesis. These results prompt us to consider 6c as a potential tubulin polymerization inhibitor and is worthy for further study.