Synthesis of a 2,4,6-trisubstituted 5-cyano-pyrimidine library and evaluation of its immunosuppressive activity in a Mixed Lymphocyte Reaction assay

A series of novel pyrimidine analogues were synthesized and evaluated for immunosuppressive activity in the Mixed Lymphocyte Reaction assay, which is well-known as the in vitro model for in vivo rejection after organ transplantation. Systematic variation of the substituents at positions 2, 4 and 6 o...

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Veröffentlicht in:Bioorganic & medicinal chemistry 2013-03, Vol.21 (5), p.1209-1218
Hauptverfasser: Stella, Alessandro, Van Belle, Kristien, De Jonghe, Steven, Louat, Thierry, Herman, Jean, Rozenski, Jef, Waer, Mark, Herdewijn, Piet
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Sprache:eng
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Zusammenfassung:A series of novel pyrimidine analogues were synthesized and evaluated for immunosuppressive activity in the Mixed Lymphocyte Reaction assay, which is well-known as the in vitro model for in vivo rejection after organ transplantation. Systematic variation of the substituents at positions 2, 4 and 6 of the pyrimidine scaffold led to the discovery of 2-benzylthio-5-cyano-6-(4-methoxyphenyl)-4-morpholinopyrimidine with an IC50 value of 1.6μM in the MLR assay.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2012.12.032