Identification of fused pyrimidines as interleukin 17 secretion inhibitors
Journal article, Peer reviewed
Accepted version

Åpne
Permanent lenke
http://hdl.handle.net/11250/2599282Utgivelsesdato
2018Metadata
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- Institutt for kjemi [1431]
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Originalversjon
European Journal of Medicinal Chemistry. 2018, 155 562-578. 10.1016/j.ejmech.2018.06.019Sammendrag
Inhibiting the interleukin 17 pathway is of interest in a number of autoimmune diseases. Herein, 42 fused
pyrimidines have been evaluated as interleukin 17 secretion inhibitors using a phenotypic assay with
peripheral blood mononuclear cells. 7H-Pyrrolo [2,3-d]pyrimidin-4-amines having aryl groups at C-5 or
C-6 were found more active than the corresponding thieno- and furopyrimidines. Low cytotoxicity was
seen for the most active inhibitors. However, the pyrrolopyrimidines also inhibit interleukin 5 secretion,
suggesting that selective interleukin 17 inhibitors should rather be based on furopyrimidines. Profiling
towards a panel of 51 kinases and assays towards the retinoic acid receptor-related orphan receptor
gamma were performed in order to identify the compounds mode of action.