18193-72-1Relevant articles and documents
Design, synthesis and biological evaluation of novel uracil derivatives bearing 1, 2, 3-triazole moiety as thymidylate synthase (TS) inhibitors and as potential antitumor drugs
Lu, Guo-qing,Li, Xin-yang,Mohamed O, Kamara,Wang, Depu,Meng, Fan-hao
, p. 282 - 296 (2019/03/27)
Research on thymidylate synthase inhibitors has been a hot spot for anticancer drug development. Here, based on the structures and pharmacological properties of two types of TS inhibitors, through a molecular assembly principle of drugs design, we designed and synthesized a series of 30 novel uracil derivatives as TS inhibitors. The antiproliferative ability of these compounds was evaluated against four cancer cell lines (A549, OVCAR-3, SGC-7901, and HepG2) by the MTT assay. Most of them showed excellent activities against all the tested cell lines. Furthermore, hTS assay results showed that these compounds have the unique ability to inhibit hTS activity in vitro. Notably, compound 13j exhibited the most potent activity against A549 cells (IC50 = 1.18 μM) and extremely prominent enzyme inhibition (IC50 = 0.13 μM), which was superior to the pemetrexed (PTX, IC50 = 3.29 μM and IC50 = 2.04 μM). Flow cytometric analysis showed the compound 13j could inhibit A549 cells proliferation by arresting the cell cycle in the G1/S phase, then induced the cell apoptosis. Further western blot analysis showed that compound 13j could down-regulate the cycle checkpoint proteins cyclin D1 and cyclin E to inhibit the cell cycle progression, and then induce intrinsic apoptosis by activating caspase-3, and reducing the ratio of bcl-2/bax. All of these results demonstrated that this new structure has potential drug-making properties and provides new ideas for drug development.
Convenient and stereoselective synthesis of (Z)-1-bromo-1-alkenes by microwave-induced reaction
Kuang, Chunxiang,Senboku, Hisanori,Tokuda, Masao
, p. 3893 - 3896 (2007/10/03)
(Z)-1-Bromo-1-alkenes were stereoselectively prepared in high yields in a short reaction time (0.2-1.0 min) by microwave irradiation of the corresponding 2,3-dibromoalkanoic acids in DMF in the presence of triethylamine.
Iodide-induced Debromination of Cinnamic Acid and Substituted Cinnamic Acid Dibromides in 2-Methoxyethanol
Subramanian, K.,Mathai, I. M.
, p. 909 - 911 (2007/10/02)
The second order rate constants for the iodide-induced debromination of cinnamic acid and substituted cinnamic acid dibromides in 2-methoxyethanol are reported; the reactivities follow the order: p-OCH3 > o-CH3 > p-CH3 > p-NO2 > p-Cl > m-NO2 > -H > m-CH3 > m-OCH3 > o-Cl.The m-CH3 and p-Cl derivatives have higher enthalpies and lower negative entropies of activation whereas methoxy substituted derivatives are characterised by lower enthalpies and higher negative entropies of activation than the unsubstituted acid.The free energy of activation is nearly constant.
