2. Academic Validation
  3. Identification of fused pyrimidines as interleukin 17 secretion inhibitors

Identification of fused pyrimidines as interleukin 17 secretion inhibitors

  • Eur J Med Chem. 2018 Jul 15:155:562-578. doi: 10.1016/j.ejmech.2018.06.019.
Ann Christin Reiersølmoen 1,  Jin Han 2,  Eirik Sundby 3,  Bård Helge Hoff 4
Affiliations

Affiliations

  • 1 Department of Chemistry, Norwegian University of Science and Technology, Høgskoleringen 5, NO-7491, Trondheim, Norway. Electronic address: ann.c.reiersolmoen@ntnu.no.
  • 2 Department of Chemistry, Norwegian University of Science and Technology, Høgskoleringen 5, NO-7491, Trondheim, Norway; GlucoSet AS, Richard Birkelandsvei 2B, 7034, Trondheim, Norway. Electronic address: Jin.Han@ntnu.no.
  • 3 Department of Material Science, Norwegian University of Science and Technology, Høgskoleringen 5, NO-7491, Norway. Electronic address: Eirik.Sundby@ntnu.no.
  • 4 Department of Chemistry, Norwegian University of Science and Technology, Høgskoleringen 5, NO-7491, Trondheim, Norway. Electronic address: bard.helge.hoff@chem.ntnu.no.
PMID: 29909341 DOI: 10.1016/j.ejmech.2018.06.019
Abstract

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.

Keywords

Furopyrimidine; Interleukin 17 secretion; Interleukin 5; Pyrrolopyrimidine; Thienopyrimidine.

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