6-Dimethylamino 1H-Pyrazolo[3,4- d]pyrimidine derivatives as new inhibitors of inflammatory mediators in intact cells

• Published in: Bioorganic & medicinal chemistry 2003-03, Vol.11 (6), p.863-868
• Main Authors: Quintela, José M, Peinador, Carlos, González, Liliana, Devesa, Isabel, Ferrándiz, M.Luisa, Alcaraz, Maria J, Riguera, Ricardo
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blotting, Western; Bones, joints and connective tissue. Antiinflammatory agents; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Humans; Inflammation Mediators - antagonists & inhibitors; Isoenzymes - metabolism; Leukocytes - drug effects; Leukotriene B4 - metabolism; Lipopolysaccharides - pharmacology; Luminescent Measurements; Macrophages, Peritoneal - drug effects; Magnetic Resonance Spectroscopy; Medical sciences; Membrane Proteins; Mice; Pancreatic Elastase - metabolism; Pharmacology. Drug treatments; Prostaglandin-Endoperoxide Synthases - metabolism; Pyrazoles - chemical synthesis; Pyrazoles - pharmacology; Pyrimidines - chemical synthesis; Pyrimidines - pharmacology; Structure-Activity Relationship
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/S0968-0896(02)00562-X

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. The synthesis and effect of pyrazolo[3,4- d]pyrimidines on murine macrophages and human neutrophils are described. Several compounds are potent PGE 2 inhibitors.