Some N-phenyl- (7a-10a) and N-benzyl-substituted (7b-10b) amido analogs of cyclooxygenase (COX-2) selective tricyclic non-steroidal anti-inflammatory drugs have been synthesized with the aim to obtain information on the structural requirements for the COX-inhibitory activity. Compounds 7-10 were tested in vitro for their inhibitory properties only towards COX-2 enzyme by measuring prostaglandin E2 (PGE2) production on activated J774.2 macrophages. Some of the new compounds (7a, 8a, 9a and 9b) showed a modest activity, with percentage inhibition values near 30% at a concentration of 10 microM. These data have been tentatively explained by a conformational study which indicates that at least the N-phenyl-substituted amides 7a-9a present steric hindrances which may prevent a good interaction with COX-2 active site.
|Autori interni:||RAPPOSELLI, SIMONA|
ORTORE, GABRIELLA MARIA PIA
|Autori:||S. RAPPOSELLI; A. LAPUCCI; F. MINUTOLO; E. ORLANDINI; G. ORTORE; M. PINZA; A. BALSAMO|
|Titolo:||Synthesis and COX2 inhibitory properties of N-Phenyl-and N-benzyl-substituted amides of 2-(4-methylsulfonylphenyl)cyclopent-1-ene-1-carboxylic acid and of their pyrazole, thiophene, and isoxazole analogs|
|Anno del prodotto:||2004|
|Digital Object Identifier (DOI):||10.1016/j.farmac.2003.09.003|
|Appare nelle tipologie:||1.1 Articolo in rivista|