Discovery of selective PDE4B inhibitors

被引：85

作者：

Naganuma, Kenji ^{[1
]}

Omura, Akifumi ^{[1
]}

Maekawara, Naomi ^{[1
]}

Saitoh, Masahiro ^{[1
]}

Ohkawa, Naoto ^{[1
]}

Kubota, Takashi ^{[1
]}

Nagumo, Hiromitsu ^{[1
]}

Kodama, Toshiyuki ^{[1
]}

Takemura, Masayoshi ^{[1
]}

Ohtsuka, Yuji ^{[1
]}

Nakamura, Junji ^{[1
]}

Tsujita, Ryuichi ^{[1
]}

Kawasaki, Koh ^{[1
]}

Yokoi, Hirotsugu ^{[1
]}

Kawanishi, Masashi ^{[1
]}

机构：

[1] Asahi Kasei Pharma Corp, Pharmaceut Res Ctr, Izunokuni, Shizuoka 4102321, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 12期

关键词：

PDE4B; Neutrophilia; 2-Arylpyrimidine; PHOSPHODIESTERASE; 4D; ASTHMA; TARGET;

D O I：

10.1016/j.bmcl.2009.04.121

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In this study the first PDE4B selective inhibitor is described. Optimization of lead 2-arylpyrimidine derivatives afforded a series of potent PDE4B inhibitors with >100-fold selectivity over the PDE4D isozyme. With a good pharmacokinetic profile, a selected compound exhibited potent anti-inflammatory effects in vivo and showed less emesis compared with Cilomilast. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：3174 / 3176

页数：3

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