Nitrooxymethyl-Substituted Analogues of Celecoxib: Synthesis and Pharmacological Characterization

被引：16

作者：

Boschi, Donatella ^{[1
]}

Lazzarato, Loretta ^{[1
]}

Rolando, Barbara ^{[1
]}

Filieri, Andrea ^{[1
]}

Cena, Clara ^{[1
]}

Di Stilo, Antonella ^{[1
]}

Fruttero, Roberta ^{[1
]}

Gasco, Alberto ^{[1
]}

机构：

[1] Univ Turin, Dipartimento Sci & Tecnol Farmaco, I-10125 Turin, Italy

来源：

CHEMISTRY & BIODIVERSITY | 2009年 / 6卷 / 03期

关键词：

NITRIC-OXIDE; CYCLOOXYGENASE INHIBITION; BIOLOGICAL EVALUATION; SELECTIVE INHIBITORS; COX-2; PYRAZOLES; COXIBS; OLD;

D O I：

10.1002/cbdv.200800307

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：369 / 379

页数：11

共 20 条

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