33948-22-0Relevant articles and documents
Synthesis and Biological Evaluation of Celastrol Derivatives with Improved Cytotoxic Selectivity and Antitumor Activities
Feng, Jia-Hao,He, Qi-Wei,Hou, Ji-Qin,Hu, Xiao-Long,Long, Huan,Wang, Bao-Lin,Wang, Hao,Wang, Quan,Wang, Rong,Ye, Wen-Cai,Zhang, Li-Xin,Zhang, Xiao-Qi
, p. 1954 - 1966 (2021/07/20)
Cdc37 associates kinase clients to Hsp90 and promotes the development of cancers. Celastrol, a natural friedelane triterpenoid, can disrupt the Hsp90-Cdc37 interaction to provide antitumor effects. In this study, 31 new celastrol derivatives, 2a - 2d , 3a - 3g , and 4a - 4t , were designed and synthesized, and their Hsp90-Cdc37 disruption activities and antiproliferative activities against cancer cells were evaluated. Among these compounds, 4f , with the highest tumor cell selectivity (15.4-fold), potent Hsp90-Cdc37 disruption activity (IC50= 1.9 μM), and antiproliferative activity against MDA-MB-231 cells (IC50= 0.2 μM), was selected as the lead compound. Further studies demonstrated 4f has strong antitumor activities both in vitro and in vivo through disrupting the Hsp90-Cdc37 interaction and inhibiting angiogenesis. In addition, 4f exhibited less toxicity than celastrol and showed a good pharmacokinetics profile in vivo. These findings suggest that 4f may be a promising candidate for development of new cancer therapies.
Method for synthesizing carbamazepine
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Paragraph 0008; 0009; 0010, (2018/12/13)
The invention discloses a method for synthesizing carbamazepine. The method takes iminodibenzyl and chlorobenzene as raw materials and comprises the following steps: introducing triphosgene to obtainacyl chloride, performing bromination with bromine to obtain bromide, performing ammoniation with ammonium hydroxide to obtain a crude product of the carbamazepine, and finally, refining the crude product with ethanol to obtain a finished product of the carbamazepine. The acyl chlorination, bromination and ammoniation adopt chlorobenzene as a reaction solvent to reduce consumption of other solvents; in the acyl chlorination reaction, the triphosgene replaces phosgene to solve the problems of safety and environmental protection in the process; the obtained acyl chloride is not separated and isdirectly subjected to bromination dehydrogenation and ammoniation reaction to lower the operation cost; the yield of each step of the synthesis process is 93% or higher, thereby improving the production efficiency and lowering the production cost; and the synthesis process adopts self-designed novel closed equipment to reduce the consumption of chlorobenzene and ethanol, thereby being suitable forindustrial production.
Synthetic method for carbamazepine intermediate iminostilbene carbonyl chloride
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Paragraph 0020; 0021; 0022; 0023; 0024; 0025; 0026-0035, (2017/04/28)
The invention discloses a synthetic method for a carbamazepine intermediate, i.e., iminostilbene carbonyl chloride. The synthetic method is characterized by comprising the following steps: adding iminodibenzylcarbonyl chloride, chlorobenzene, an initiator and a phase-transfer catalyst, carrying out heating to 90 to 93 DEG C, adding a bromination agent for a reaction, then carrying out heating to 95 to 100 DEG C, carrying out reflux for 4 h at the same time and subjecting a reaction solution obtained after completion of reflux to post-treatment so as to obtain iminostilbene carbonyl chloride. The synthetic method has the beneficial effects that since the phase-transfer catalyst is added, escape of hydrogen bromide is reduced, the utilization rate of bromine is increased, atmospheric pollution is alleviated and production cost is lowered; and the method is suitable for industrial production.