51490-05-2Relevant articles and documents
Design, synthesis and biological evaluation of novel pyrrolidone-based derivatives as potent p53-MDM2 inhibitors
Si, Dongjuan,Luo, Huijuan,Zhang, Xiaomeng,Yang, Kundi,Wen, Hongmei,Li, Wei,Liu, Jian
, (2021/08/27)
Inhibition of the interactions of the tumor suppressor protein p53 with its negative regulators MDM2 in vitro and in vivo, representing a valuable therapeutic strategy for cancer treatment. The natural product chalcone exhibited moderate inhibitory activity against MDM2, thus based on the binding mode between chalcone and MDM2, a hit unsaturated pyrrolidone scaffold was obtained through virtual screening. Several unsaturated pyrrolidone derivatives were synthesized and biological evaluated. As a result, because the three critical hydrophobic pockets of MDM2 were occupied by the substituted-phenyl linked at the pyrrolidone fragment, compound 4 h demonstrated good binding affinity with the MDM2. Additionally, compound 4 h also showed excellent antitumor activity and selectivity, and no cytotoxicity against normal cells in vitro. The further antitumor mechanism studies were indicated that compound 4 h could successfully induce the activation of p53 and corresponding downstream p21 proteins, thus successfully causing HCT116 cell cycle arrest in the G1/M phase and apoptosis. Thus, the novel unsaturated pyrrolidone p53-MDM2 inhibitors could be developed as novel antitumor agents.
Diazaphosphinyl radical-catalyzed deoxygenation of α-carboxy ketones: A new protocol for chemo-selective C-O bond scission: Via mechanism regulation
Cheng, Jin-Pei,Yang, Jin-Dong,Zhang, Jingjing
, p. 8476 - 8481 (2020/09/07)
C-O bond cleavage is often a key process in defunctionalization of organic compounds as well as in degradation of natural polymers. However, it seldom occurs regioselectively for different types of C-O bonds under metal-free mild conditions. Here we report a facile chemo-selective cleavage of the α-C-O bonds in α-carboxy ketones by commercially available pinacolborane under the catalysis of diazaphosphinane based on a mechanism switch strategy. This new reaction features high efficiency, low cost and good group-tolerance, and is also amenable to catalytic deprotection of desyl-protected carboxylic acids and amino acids. Mechanistic studies indicated an electron-transfer-initiated radical process, underlining two crucial steps: (1) the initiator azodiisobutyronitrile switches originally hydridic reduction to kinetically more accessible electron reduction; and (2) the catalytic phosphorus species upconverts weakly reducing pinacolborane into strongly reducing diazaphosphinane. This journal is
Method for preparing diphenylethanone from benzyl alcohol through photocatalytic one-step method
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Paragraph 0041; 0042, (2018/09/13)
The present invention relates to a method for preparing diphenylethanone from benzyl alcohol through a photocatalytic one-step method. According to the method, diphenylethanone is directly prepared byusing inexpensive benzyl alcohol as a raw material under the action of a solid photocatalyst; and the reaction process comprises: mixing benzyl alcohol, a catalyst and an acetonitrile solvent are mixed, placing in a pressure container, replacing with an inert gas, and carrying out illumination stirring at a room temperature, wherein the reaction time is more than 1 h, the catalyst is easily separated from the reaction system after the reaction and can be recycled multiple times, and the separation yield of diphenylethanone is up to 81%.
