Development of orally bioavailable bicyclic pyrazolones as inhibitors of tumor necrosis factor-α production

被引：138

作者：

Clark, MP ^{[1
]}

Laughlin, SK ^{[1
]}

Laufersweiler, MJ ^{[1
]}

Bookland, RG ^{[1
]}

Brugel, TA ^{[1
]}

Golebiowski, A ^{[1
]}

Sabat, MP ^{[1
]}

Townes, JA ^{[1
]}

VanRens, JC ^{[1
]}

Djung, JF ^{[1
]}

Natchus, MG ^{[1
]}

De, B ^{[1
]}

Hsieh, LC ^{[1
]}

Xu, SC ^{[1
]}

Walter, RL ^{[1
]}

Mekel, MJ ^{[1
]}

Heitmeyer, SA ^{[1
]}

Brown, KK ^{[1
]}

Juergens, K ^{[1
]}

Taiwo, YO ^{[1
]}

Janusz, MJ ^{[1
]}

机构：

[1] Procter & Gamble Pharmaceut, Mason, OH 45040 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 11期

关键词：

D O I：

10.1021/jm049968m

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

2-Aryl-3-pyrimidinyl based tumor necrosis factor-alpha (TNF-alpha) inhibitors, which contain a novel bicyclic pyrazolope core, are described. Many showed low-nanomolar activity against lipopolysaccharide-induced TNF-alpha production in monocytic cells. Secondary screening data are presented for the pyrimidinyl bicyclic pyrazolones. Several of these analogues showed good oral bioavailability in rat and efficacy in the rat iodoacetate in vivo model.

引用

页码：2724 / 2727

页数：4

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