588-96-5Relevant articles and documents
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Michaelis
, p. 258 (1894)
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Synthesis, evaluation and in silico studies of novel BRD4 bromodomain inhibitors bearing a benzo[d]isoxazol scaffold
Zhang, Maofeng,Liu, Zhuyun,Wang, Lizhong,Li, Yan,Ma, Yonggang
, (2021/02/12)
Abstract: The BRD4 protein is associated with various diseases, which has been an attractive target for the treatment of cancer and inflammation. This paper is a follow-up to our previous studies, in which we report the structure-based design, synthesis, and evaluation of a new class of small-molecule BRD4 bromodomain inhibitors bearing a benzo[d]isoxazol scaffold. The SARs focused on exploration of the 2′ or 3′ position to afford novel inhibitors that may avoid potential metabolically unstable site. The most potent inhibitor 13f exhibited high binding affinity to BRD4(1) with a ΔTm value of 7.8 °C as evaluated in thermal shift assay (TSA). The potent activity was also demonstrated by a peptide competition assay with an IC50 value of 0.21?μM. The docking studies revealed the binding mode of the compounds with the active site of BRD4(1). In addition, in silico predictions indicated that these compounds possessed good drug-likeness and pharmacokinetic profile. Graphic abstract: This paper is a follow-up to our previous studies, in which we report the structure-based design,synthesis, and evaluation of a new class of small-molecule BRD4 bromodomain inhibitors bearing a benzo[d]isoxazolscaffold.[Figure not available: see fulltext.].
Preparation method of p-bromophenylalkyl ether
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Paragraph 0044-0058, (2020/07/15)
The invention relates to a preparation method of p-bromophenylalkyl ether, wherein the preparation method comprises the steps: carrying out bromination reaction on phenylalkyl ether, hydrobromic acidand an oxidant in an organic solvent to prepare p-bromophenylalkyl ether. A chlorinated non-polar solvent is used as a reaction solvent, so that the para-position substitution selectivity of the bromination reaction is greatly improved, the yield of the bromination reaction is remarkably improved, p-bromophenylalkyl ether is prepared by replacing an etherification reaction route with the bromination reaction, toxic diethyl sulfate does not need to be used in the preparation process, and potential safety hazards are avoided; meanwhile, the dosage of the solvent is greatly reduced, the loading capacity of the raw materials of a reaction kettle is greatly improved, the production efficiency is greatly improved, and the production time is shortened; the post-treatment is simple, the reaction solvent can be recycled, and the comprehensive production cost is reduced; the method has the advantages of easily available raw materials, simple operation, low risk, high yield, high product purity,small pollution of the whole process, and suitableness for large-scale industrial production.