2042-14-0Relevant articles and documents
Aryl phenol compound as well as synthesis method and application thereof
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Paragraph 0133-0136, (2021/05/12)
The invention discloses a synthesis method of an aryl phenol compound shown as a formula (3). All systems are carried out in an air or nitrogen atmosphere, and visible light is utilized to excite a photosensitizer for catalyzation. In a reaction solvent, ArNR1R2 as shown in a formula (1) and water as shown in a formula (2) are used as reaction raw materials and react under the auxiliary action of acid to obtain the aryl phenol compound as shown in a formula (3). The ArNR1R2 in the formula (1) can be primary amine and tertiary amine, can also be steroid and amino acid derivatives, and can also be drugs or derivatives of propofol, paracetamol, ibuprofen, oxaprozin, indomethacin and the like. The synthesis method has the advantages of cheap and easily available raw materials, simple reaction operation, mild reaction conditions, high reaction yield and good compatibility of substrate functional groups. The fluid reaction not only can realize amplification of basic chemicals, but also can realize amplification of fine chemicals, such as synthesis of drugs propofol and paracetamol. The invention has wide application prospect and use value.
Cell-Based Optimization of Covalent Reversible Ketoamide Inhibitors Bridging the Unprimed to the Primed Site of the Proteasome β5 Subunit
Stubba, Daniel,Bensinger, Dennis,Steinbacher, Janika,Proskurjakov, Lilia,Salcedo Gómez, álvaro,Schmidt, Uwe,Roth, Stefan,Schmitz, Katja,Schmidt, Boris
supporting information, p. 2005 - 2022 (2019/11/22)
The ubiquitin-proteasome system (UPS) is an established therapeutic target for approved drugs to treat selected hematologic malignancies. While drug discovery targeting the UPS focuses on irreversibly binding epoxyketones and slowly-reversibly binding boronates, optimization of novel covalent-reversibly binding warheads remains largely unattended. We previously reported α-ketoamides to be a promising reversible lead motif, yet the cytotoxic activity required further optimization. This work focuses on the lead optimization of phenoxy-substituted α-ketoamides combining the structure-activity relationships from the primed and the non-primed site of the proteasome β5 subunit. Our optimization strategy is accompanied by molecular modeling, suggesting occupation of P1′ by a 3-phenoxy group to increase β5 inhibition and cytotoxic activity in leukemia cell lines. Key compounds were further profiled for time-dependent inhibition of cellular substrate conversion. Furthermore, the α-ketoamide lead structure 27 does not affect escape response behavior in Danio rerio embryos, in contrast to bortezomib, which suggests increased target specificity.
USE OF DDX3 INHIBITORS AS ANTIPROLIFERATIVE AGENTS
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Page/Page column 85, (2017/10/30)
The present invention refers to compounds of formula I or II endowed with DDX3 inhibitory activity, relative pharmaceutical compositions and their use as antihyperproliferative agents. (I) or (II)
