Synthesis and in vitro evaluation of 2-amino-4-N-piperazinyl-6-(3,4-dimethoxyphenyl)-pteridines as dual immunosuppressive and anti-inflammatory agents

Steven De Jonghe; Arnaud Marchand; Ling-Jie Gao; Agnes Calleja; Eva Cuveliers; Ilse Sienaert; Jean Herman; Gavin Clydesdale; Hassane Sefrioui; Yuan Lin; Wolfgang Pfleiderer; Mark Waer; Piet Herdewijn

doi:10.1016/j.bmcl.2010.11.053

Synthesis and in vitro evaluation of 2-amino-4-N-piperazinyl-6-(3,4-dimethoxyphenyl)-pteridines as dual immunosuppressive and anti-inflammatory agents

Bioorg Med Chem Lett. 2011 Jan 1;21(1):145-9. doi: 10.1016/j.bmcl.2010.11.053. Epub 2010 Nov 16.

Authors

Steven De Jonghe¹, Arnaud Marchand, Ling-Jie Gao, Agnes Calleja, Eva Cuveliers, Ilse Sienaert, Jean Herman, Gavin Clydesdale, Hassane Sefrioui, Yuan Lin, Wolfgang Pfleiderer, Mark Waer, Piet Herdewijn

Affiliation

¹ 4AZA Bioscience, Kapucijnenvoer 33, 3000 Leuven, Belgium.

PMID: 21131199
DOI: 10.1016/j.bmcl.2010.11.053

Abstract

Screening of a pteridine-based compound library led to the identification of compounds exhibiting immunosuppressive as well as anti-inflammatory activity. Optimization afforded a series of 2-amino-4-N-piperazinyl-6-(3,4-dimethoxyphenyl)pteridine analogues. The most potent congeners in this series displayed low nM IC(50) values in the Mixed Lymphocyte Reaction (MLR) assay. In addition, these compounds also have potent anti-inflammatory activity as measured in the Tumor Necrosis Factor (TNF) assay.

MeSH terms

Anti-Inflammatory Agents / chemical synthesis*
Anti-Inflammatory Agents / chemistry
Anti-Inflammatory Agents / pharmacology
Drug Evaluation, Preclinical
Immunosuppressive Agents / chemical synthesis*
Immunosuppressive Agents / chemistry
Immunosuppressive Agents / pharmacology
Pteridines / chemical synthesis
Pteridines / chemistry*
Pteridines / pharmacology
Structure-Activity Relationship

Substances

Anti-Inflammatory Agents
Immunosuppressive Agents
Pteridines