6-Dimethylamino 1H-pyrazolo[3,4-d]pyrimidine derivatives as new inhibitors of inflammatory mediators in intact cells.
The synthesis of 6-dimethylamino 1H-pyrazolo[3,4-d]pyrimidines substituted at positions 1 and 4, and their effects on murine macrophage and human neutrophil functions are described. Several compounds and especially 4b-6b are potent inhibitors of PGE(2) generation in murine macrophages. This action is related to a direct effect on COX-2 activity without affecting the enzyme expression. Some of these compounds also inhibited COX-1 and COX-2 in human monocytes and 4b showed selectivity for COX-2 inhibition.
Quintela
José M
JM
Departamento de Química Fundamental e Industrial, Facultad de Ciencias, Universidad de La Coruña, La Coruña 15071, Spain.
Peinador
Carlos
C
González
Liliana
L
Devesa
Isabel
I
Ferrándiz
M Luisa
ML
Alcaraz
Maria J
MJ
Riguera
Ricardo
R
D000818:Animals; D015153:Blotting, Western; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D007527:Isoenzymes / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects; D007975:Leukotriene B4 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008163:Luminescent Measurements; D017737:Macrophages, Peritoneal / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins; D051379:Mice; D010196:Pancreatic Elastase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D018836:Inflammation Mediators; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011720:Pyrazoles; D011743:Pyrimidines; D007975:Leukotriene B4; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D010196:Pancreatic Elastase