129277-08-3Relevant articles and documents
Development of novel amides as noncovalent inhibitors of immunoproteasomes
Ettari, Roberta,Cerchia, Carmen,Maiorana, Santina,Guccione, Manuela,Novellino, Ettore,Bitto, Alessandra,Grasso, Silvana,Lavecchia, Antonio,Zappalà, Maria
, p. 842 - 852 (2019)
The development of immunoproteasome-selective inhibitors is a promising strategy for treating hematologic malignancies, autoimmune and inflammatory diseases. In this context, we report the design, synthesis, and biological evaluation of a new series of amide derivatives as immunoproteasome inhibitors. Notably, the designed compounds act as noncovalent inhibitors, which might be a promising therapeutic option because of the lack of drawbacks and side effects associated with irreversible inhibition. Among the synthesized compounds, we identified a panel of active inhibitors with Ki values in the low micromolar or sub-micromolar ranges toward the b5i and/or b1i subunits of immunoproteasomes. One of the active compounds was shown to be the most potent and selective inhibi-tor with a Ki value of 21 nm against the single b1i subunit. Docking studies allowed us to determine the mode of binding of the molecules in the catalytic site of immunoproteasome subunits.
Imidazole compounds
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Page column 8, (2008/06/13)
Imidazole compounds having adenosine deaminase inhibitory activity represented by formula (I) wherein R1is hydrogen, hydroxy, protected hydroxy, or aryl optionally substituted with suitable substituent(s); R2is hydrogen or lower alkyl; R3is hydroxy or protected hydroxy; R4is cyano, (hydroxy)iminoamino(lower)alkyl, carboxy, protected carboxy, heterocyclic group optionally substituted with amino, or carbamoyl optionally substituted with suitable substituent(s); and —A— is —Q— or —O—Q—, wherein Q is single bond or lower alkylene, provided that when R2is lower alkyl, then R1is hydroxy, protected hydroxy, or aryl optionally substituted with suitable substituent(s), its prodrug, or their salt. The compounds are useful for treating and/or preventing diseases for which adenosine is effective.
