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.
N-heterocyclic (4-phenylpiperazin-1-yl)methanones derived from phenoxazine and phenothiazine as highly potent inhibitors of tubulin polymerization
Prinz, Helge,Ridder, Ann-Kathrin,Vogel, Kirsten,B?hm, Konrad J.,Ivanov, Igor,Ghasemi, Jahan B.,Aghaee, Elham,Müller, Klaus
, p. 749 - 766 (2017/02/05)
We report here a series of 27 10-(4-phenylpiperazin-1-yl)methanones derived from tricyclic heterocycles which were screened for effects on tumor cell growth, inhibition of tubulin polymerization, and induction of cell cycle arrest. Several analogues, among them the 10-(4-(3-methoxyphenyl)piperazine-1-carbonyl)-10H-phenoxazine-3-carbonitrile (16o), showed excellent antiproliferative properties, with low nanomolar GI50 values (16o, mean GI50 of 3.3 nM) against a large number (93) of cancer cell lines. Fifteen compounds potently inhibited tubulin polymerization. Analysis of cell cycle by flow cytometry revealed that inhibition of tumor cell growth was related to an induction of G2/M phase cell cycle blockade. Western blotting and molecular docking studies suggested that these compounds bind efficiently to β-tubulin at the colchicine binding site. Our studies demonstrate the suitability of the phenoxazine and phenothiazine core and also of the phenylpiperazine moiety for the development of novel and potent tubulin polymerization inhibitors.
