Synthesis, immunosuppressive activity and structure-activity relationship study of a new series of 4-N-piperazinyl-thieno[2,3-d]pyrimidine analogues.
The synthesis of a new series of 4-N-piperazinyl-thieno[2,3-d]pyrimidines is described. The synthetic route allows introducing structural variety at positions 2, 4 and 6 of the scaffold. Evaluation of their immunosuppressive activity in a Mixed Lymphocyte Reaction (MLR) assay revealed that the most potent compound has an IC(50)-value of 66 nM and therefore deserves attention for further medicinal chemistry optimization.
Jang
Mi-Yeon
MY
Catholic University of Leuven, Rega Institute, Laboratory of Medicinal Chemistry, Minderbroedersstraat 10, 3000 Leuven, Belgium.
De Jonghe
Steven
S
Van Belle
Kristien
K
Louat
Thierry
T
Waer
Mark
M
Herdewijn
Piet
P
D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D007166:Immunosuppressive Agents; D010879:Piperazines; D011743:Pyrimidines