Synthesis and in vitro evaluation of 2-amino-4-N-piperazinyl-6-(3,4-dimethoxyphenyl)-pteridines as dual immunosuppressive and anti-inflammatory agents.
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.
4AZA Bioscience, Kapucijnenvoer 33, 3000 Leuven, Belgium.
Steven
S
De Jonghe
Arnaud
A
Marchand
Ling-Jie
LJ
Gao
Agnes
A
Calleja
Eva
E
Cuveliers
Ilse
I
Sienaert
Jean
J
Herman
Gavin
G
Clydesdale
Hassane
H
Sefrioui
Yuan
Y
Lin
Wolfgang
W
Pfleiderer
Mark
M
Waer
Piet
P
Herdewijn
D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011621:Pteridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D011621:Pteridines