2010-15-3Relevant articles and documents
2-Polystyrylsulfonyl ethanol supports for the solid-phase syntheses of hydantoins and ureas
Huang, Wenqiang,Cheng, Shaoling,Sun, Weimin
, p. 1973 - 1974 (2001)
Reaction of sodium polystyrylsulfinate 1 with 2-chloroethanol gave the 2-arylsulfonyl ethanol resin 2, which was converted to the polymer-supported amine 5. Amine 5 was coupled with an isocyanate or an isothiocyanate to give the polymer-supported urea der
Identification of 2-thioxoimidazolidin-4-one derivatives as novel noncovalent proteasome and immunoproteasome inhibitors
Maccari, Rosanna,Ettari, Roberta,Adornato, Ilenia,Na?, Alexandra,Wolber, Gerhard,Bitto, Alessandra,Mannino, Federica,Aliquò, Federica,Bruno, Giuseppe,Nicolò, Francesco,Previti, Santo,Grasso, Silvana,Zappalà, Maria,Ottanà, Rosaria
, p. 278 - 283 (2018)
This paper describes the design, synthesis, and biological evaluation of 2-thioxoimidazolidin-4-one derivatives as inhibitors of proteasome and immunoproteasome, potential targets for the treatment of hematological malignancies. In particular, we focused our efforts on the design of noncovalent inhibitors, which might be a promising therapeutic option potentially devoid of drawbacks and side-effects related to irreversible inhibition. Among all the synthesized compounds, we identified a panel of active inhibitors with Ki values towards one or two chymotrypsin-like activities of proteasome (β5c) and immunoproteasome (β5i and β1i subunits) in the low micromolar range. Docking studies suggested a unique binding mode of the molecules in the catalytic site of immunoproteasome proteolytic subunits.
Design and evaluation of non-carboxylate 5-arylidene-2-thioxo-4-imidazolidinones as novel non-competitive inhibitors of protein tyrosine phosphatase 1B
Ottanà, Rosaria,Paoli, Paolo,Lori, Giulia,Adornato, Ilenia,Previti, Santo,Na?, Alexandra,Wolber, Gerhard,Maccari, Rosanna
, (2019/09/06)
Protein tyrosine phosphatase 1B (PTP1B) acts as a negative regulator of insulin and leptin signalling and is crucially involved in the development of type 2 diabetes mellitus, obesity, cancer and neurodegenerative diseases. Pursuing our efforts to identify PTP1B inhibitors endowed with drug-like properties, we designed and evaluated 3-aryl-5-arylidene-2-thioxo-4-imidazolidinones (7) as a novel class of non-carboxylate PTP1B inhibitors. In agreement with our design, kinetic studies demonstrated that selected compounds 7 act as reversible, non-competitive inhibitors of the target enzyme at low micromolar concentrations. Accordingly, molecular docking experiments suggested that these inhibitors can fit an allosteric site of PTP1B that we previously individuated. Moreover, cellular assays demonstrated that compound 7e acts as a potent insulin-sensitizing agent in human liver HepG2 cells. Taken together, our results showed that these non-competitive PTP1B inhibitors can be considered promising lead compounds aimed to enhance druggability of the target enzyme and identify novel antidiabetic drugs.
Simple and Efficient Synthesis of 5-Substituted-3-phenyl-2-thioxoimidazolidin-4-one Derivatives from S -Amino Acids and Phenylisothiocyanate in et 3N/DMF-H 2O
Jangale, Asha D.,Wagh, Yogesh B.,Tayade, Yogesh A.,Dalal, Dipak S.
supporting information, p. 1876 - 1886 (2015/08/03)
A concise approach for the transformation of various S-amino acids into the 5-alkyl-3-phenyl-2-thioxoimidazolidin-4-one heterocycles using phenylisothiocyanate is described. Phenylthiohydantoins of amino acid were synthesized at room temperature in Et3N/DMF-H2O with easy workup and excellent yields.
