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 of the pyrimidine scaffold led to the discovery of 2-benzylthio-5-cyano-6-(4-methoxyphenyl)-4-morpholinopyrimidine with an IC(50) value of 1.6 μM in the MLR assay.
KU Leuven, Interface Valorisation Platform, Kapucijnenvoer 33, 3000 Leuven, Belgium.
Alessandro
A
Stella
Kristien
K
Van Belle
Steven
S
De Jonghe
Thierry
T
Louat
Jean
J
Herman
Jef
J
Rozenski
Mark
M
Waer
Piet
P
Herdewijn
D006801:Humans; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D019169:Jurkat Cells; D007959:Lymphocyte Culture Test, Mixed; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D007166:Immunosuppressive Agents; D011743:Pyrimidines; C030986:pyrimidine