Synthesis and SAR of a new series of COX-2-selective inhibitors:: Pyrazolo[1,5-α]pyrimidines

被引：177

作者：

Almansa, C ^{[1
]}

de Arriba, AF ^{[1
]}

Cavalcanti, FL ^{[1
]}

Gómez, LA ^{[1
]}

Miralles, A ^{[1
]}

Merlos, M ^{[1
]}

García-Rafanell, J ^{[1
]}

Forn, J ^{[1
]}

机构：

[1] J Uriach & Cia SA, Res Ctr, Barcelona 08026, Spain

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2001年 / 44卷 / 03期

关键词：

D O I：

10.1021/jm0009383

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and pharmacological activity of a series of bicyclic pyrazolo[1,5-a]pyrimidines as potent and selective cyclooxygenase-2 (COX-2) inhibitors are described. The new compounds were evaluated both in vitro (COX-1 and COX-2 inhibition in human whole blood) and in vive (carrageenan-induced paw edema and air-pouch model). Modification of the pyrimidine substituents showed that 6,7-disubstitution provided the best activity and led to the identification of 3-(4-fluorophenyl)-6,7-dimethyl-2-(4-methylsulfonylphenyl)pyrazolo[1,5-a]pyrimidine (10f) as one of the most potent and selective COX-2 inhibitor in this series.

引用

页码：350 / 361

页数：12

共 43 条

[1]

Ainsworth C., 1963, ORG SYNTH, V4, P536

[2] GASTROINTESTINAL DAMAGE ASSOCIATED WITH THE USE OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS [J].