Novel cyclic compounds as potent phosphodiesterase 4 inhibitors

被引：25

作者：

He, W ^{[1
]}

Huang, FC ^{[1
]}

Hanney, B ^{[1
]}

Souness, J ^{[1
]}

Miller, B ^{[1
]}

Liang, GY ^{[1
]}

Mason, J ^{[1
]}

Djuric, S ^{[1
]}

机构：

[1] Rhone Poulenc Rorer Cent Res, Dept Med Chem, Collegeville, PA 19426 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1998年 / 41卷 / 22期

关键词：

D O I：

10.1021/jm970575f

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and biological activity of a novel series of 2,2-disubstituted indan-1,3-dione-based PDE4 inhibitors are described. This structurally unique class of PDE4 inhibitors is markedly different from the known PDE4 inhibitors such as RP 73401 (2) and CDP 840 (3). Structure-activity relationship (SAR) studies led to the identification of inhibitors with nanomolar potency and oral activity in a murine endotoxemia model for TNF-alpha inhibition. Unlike other classical PDE4 inhibitors, several analogues were found to be nonemetic in a canine emesis model at intravenous doses of up to 3 mg/kg.

引用

页码：4216 / 4223

页数：8

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