SELECTIVE TYPE-IV PHOSPHODIESTERASE INHIBITORS AS ANTIASTHMATIC AGENTS - THE SYNTHESES AND BIOLOGICAL-ACTIVITIES OF 3-(CYCLOPENTYLOXY)-4-METHOXYBENZAMIDES AND ANALOGS

被引：112

作者：

ASHTON, MJ ^{[1
]}

COOK, DC ^{[1
]}

FENTON, G ^{[1
]}

KARLSSON, JA ^{[1
]}

PALFREYMAN, MN ^{[1
]}

RAEBURN, D ^{[1
]}

RATCLIFFE, AJ ^{[1
]}

SOUNESS, JE ^{[1
]}

THURAIRATNAM, S ^{[1
]}

VICKER, N ^{[1
]}

机构：

[1] RHONE POULENC RORER CENT RES,DAGENHAM RES CTR,DAGENHAM RM10 7XS,ESSEX,ENGLAND

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1994年 / 37卷 / 11期

关键词：

D O I：

10.1021/jm00037a021

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The syntheses and biological activities of a number of benzamide derivatives, designed from rolipram, which are selective inhibitors of cyclic AMP-specific phosphodiesterase (PDE IV), are described. The effects of changes to the alkoxy groups, amide linkage, and benzamide N-phenyl ring on the inhibition of the cytosolic PDE IV from pig aorta have been investigated. As a result, some highly potent and selective PDE IV inhibitors have been identified. The most potent compounds have been further evaluated for their inhibitory potencies against PDE IV obtained from and superoxide O-2(-) generation from guinea pig eosinophils in vitro. Selected compounds have also been examined for their activities in inhibiting histamine-induced bronchospasm in anaesthetized guinea pigs. 3-(Cyclopentyloxy)-N-(3,5-dichloro-4-pyridyl)-4-methoxybenzamide (15j) showed exceptional potency in all tests and may have therapeutic potential in the treatment of asthma.

引用

页码：1696 / 1703

页数：8

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