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  • Novel selective IDO1 inhibitors with isoxazolo[5,4-d]pyrimidin-4(5H)-one scaffold [Elektronski vir]
    Dolšak, Ana, farmacevtka, 1993- ...
    Indoleamine 2,3-dioxygenase 1 (IDO1) is a promising target in immunomodulation of several pathological conditions, especially cancers. Here we present the synthesis of a series of IDO1 inhibitors ... with the novel isoxazolo[5,4-d]pyrimidin-4(5H)-one scaffold. A focused library was prepared using a 6- or 7-step synthetic procedure to allow a systematic investigation of the structure-activity relationships of the described scaffold. Chemistry-driven modifications lead us to the discovery of our best-in-class inhibitors possessing p-trifluoromethyl (23), p-cyclohexyl (32), or p-methoxycarbonyl (20, 39) substituted aniline moieties with IC50 values in the low micromolar range. In addition to hIDO1, compounds were tested for their inhibition of indoleamine 2,3-dioxygenase 2 and tryptophan dioxygenase, and found to be selective for hIDO1. Our results thus demonstrate a successful study on IDO1-selective isoxazolo[5,4-d]pyrimidin-4(5H)-one inhibitors, defining promising chemical probes with a novel scaffold for further development of potent small-molecule immunomodulators.
    Source: Pharmaceuticals [Elektronski vir]. - ISSN 1424-8247 (Vol. 14, no. 3, 2021, str. 1-18)
    Type of material - e-article ; adult, serious
    Publish date - 2021
    Language - english
    COBISS.SI-ID - 57316099

    Link(s):

    https://www.mdpi.com/1424-8247/14/3/265
    Repository of the University of Ljubljana – RUL
    DOI

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