Discovery and SAR study of 2-(4-pyridylamino)thieno[3,2-d]pyrimidin-4(3H)-ones as soluble and highly potent PDE7 inhibitors

被引：11

作者：

Endo, Yusuke ^{[1
]}

Kawai, Kentaro ^{[1
]}

Asano, Takeshi ^{[1
]}

Amano, Seiji ^{[1
]}

Asanuma, Yoshihito ^{[1
]}

Sawada, Keisuke ^{[1
]}

Ogura, Keiji ^{[1
]}

Nagata, Naoya ^{[1
]}

Ueo, Noriko ^{[1
]}

Takahashi, Nobuaki ^{[1
]}

Sonoda, Yo ^{[1
]}

Kamei, Noriyuki ^{[1
]}

机构：

[1] Kaken Pharmaceut Co Ltd, Drug Res Ctr, Yamashina, Kyoto 6078042, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 03期

关键词：

Phosphodiesterase; Thienopyrimidinone; T-cell; Aqueous solubility; STRUCTURAL CLASS; DRUG DISCOVERY; PART; EFFICIENCY; DISEASE; ANALOGS; CAMP;

D O I：

10.1016/j.bmcl.2014.11.090

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The discovery and SAR study of a new series of soluble and highly potent phosphodiesterase (PDE) 7 inhibitors are described herein. We explored a new lead compound with improved solubility, which led to the discovery of a 2-(4-pyridylamino)thieno[3,2-d]pyrimidin-4(3H)-one series. The introduction of 3-piperidines at the 7-position resulted in the significant enhancement of PDE7 activity. In particular, compound 32 also showed strong PDE7 inhibitory activity; good selectivity against PDE3, 4, and 5; and good aqueous solubility. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：649 / 653

页数：5

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