Synthesis, immunosuppressive activity and structure-activity relationship study of a new series of 4-N-piperazinyl-thieno[2,3-d]pyrimidine analogues

Mi-Yeon Jang; Steven De Jonghe; Kristien Van Belle; Thierry Louat; Mark Waer; Piet Herdewijn

doi:10.1016/j.bmcl.2009.12.098

Synthesis, immunosuppressive activity and structure-activity relationship study of a new series of 4-N-piperazinyl-thieno[2,3-d]pyrimidine analogues

Bioorg Med Chem Lett. 2010 Feb 1;20(3):844-7. doi: 10.1016/j.bmcl.2009.12.098. Epub 2010 Jan 4.

Authors

Mi-Yeon Jang¹, Steven De Jonghe, Kristien Van Belle, Thierry Louat, Mark Waer, Piet Herdewijn

Affiliation

¹ Catholic University of Leuven, Rega Institute, Laboratory of Medicinal Chemistry, Minderbroedersstraat 10, 3000 Leuven, Belgium.

PMID: 20064721
DOI: 10.1016/j.bmcl.2009.12.098

Abstract

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.

Publication types

Comparative Study

MeSH terms

Dose-Response Relationship, Immunologic
Humans
Immunosuppressive Agents / chemical synthesis*
Immunosuppressive Agents / pharmacology*
Lymphocyte Culture Test, Mixed / methods
Lymphocytes / drug effects
Lymphocytes / immunology
Piperazines / chemical synthesis*
Piperazines / pharmacology*
Pyrimidines / chemical synthesis*
Pyrimidines / pharmacology*
Structure-Activity Relationship

Substances

Immunosuppressive Agents
Piperazines
Pyrimidines