Nitrooxymethyl-substituted analogues of celecoxib: synthesis and pharmacological characterization.
Nitrooxymethyl-substituted analogues of celecoxib were synthesized and tested for their cyclooxygenase (COX)-inhibiting, vasodilator, and anti-aggregatory activities, as well as for their metabolic stability in human serum and whole blood. The results showed their potency and selectivity in inhibiting the COX isoforms, evaluated in whole human blood, as well as their anti-aggregatory activity to depend closely on the position at which the NO-donor moiety is introduced. All products dilated rat aorta strips precontracted with phenylephrine in a dose-dependent manner through a cGMP-dependent mechanism. They were stable in human serum while, in blood, they were metabolically transformed, principally to the related alcohols.
Boschi
Donatella
D
Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via Pietro Giuria 9, Turin.
Lazzarato
Loretta
L
Rolando
Barbara
B
Filieri
Andrea
A
Cena
Clara
C
Di Stilo
Antonella
A
Fruttero
Roberta
R
Gasco
Alberto
A