Synthesis of new pyrrolo[2, 3-b]pyridines as a potent inhibitor of tumour necrosis factor alpha.
The MAP kinase p38 plays a key role in the biosynthesis of the inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and 1L-1beta. Accordingly, new pyrrolo[2, 3-]pyridine derivatives 5a-d were prepared from 2-amino-3-cyanopyrroles 3a-d via the intermediate propenylaminopyrroles 4a-d. Then the compounds 5a-d were tested for their ability to inhibit the production of TNF-alpha in vivo in rats. The most potent compounds 5a and 5b possess enhanced ability to inhibit the production of TNF-alpha stimulated with bacterial lipopolysaccharide.
Hilmy
Khalid Mohammed Hassan
KM
Department of Chemistry, Faculty of Science, Munoufiya University, Shebin El-Koom, Egypt. khaledhilny@hotmail.com
D000284:Administration, Oral; D000818:Animals; D004926:Escherichia coli / Q000737:chemistry / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D009363:Neoplasm Proteins / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011725:Pyridines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011758:Pyrroles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051381:Rats; D047889:Receptors, Tumor Necrosis Factor, Type II; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D008070:Lipopolysaccharides; D009363:Neoplasm Proteins; D011725:Pyridines; D011758:Pyrroles; D047889:Receptors, Tumor Necrosis Factor, Type II; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; C486292:pyrrolo(2, 3-b)pyridine