Optimization of purine based PDE1/PDE5 inhibitors to a potent and selective PDE5 inhibitor for the treatment of male ED

被引：24

作者：

Boyle, CD ^{[1
]}

Xu, R ^{[1
]}

Asberom, T ^{[1
]}

Chackalamannil, S ^{[1
]}

Clader, JW ^{[1
]}

Greenlee, WJ ^{[1
]}

Guzik, H ^{[1
]}

Hu, YQ ^{[1
]}

Hu, ZY ^{[1
]}

Lankin, CM ^{[1
]}

Pissarnitski, DA ^{[1
]}

Stamford, AW ^{[1
]}

Wang, YG ^{[1
]}

Skell, J ^{[1
]}

Kurowski, S ^{[1
]}

Vemulapalli, S ^{[1
]}

Palamanda, J ^{[1
]}

Chintala, M ^{[1
]}

Wu, P ^{[1
]}

Myers, J ^{[1
]}

Wang, P ^{[1
]}

机构：

[1] Schering Plough Res Inst, Kenilworth, NJ 07033 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 09期

关键词：

PDE5; inhibitor; erectile dysfunction; male ED; purine;

D O I：

10.1016/j.bmcl.2005.02.083

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In search of a PDE5 inhibitor for erectile dysfunction, an SAR was developed from a PDE1/PDE5 purine series of leads, which had modest PDE5 potency and poor isozyme selectivity. A compound (41) with PDE5 inhibition and in vivo activity similar to sildenafil was discovered from this effort. In addition, purine 41 demonstrated superior overall PDE isozyme selectivity when compared to the approved PDE5 inhibitors sildenafil, vardenafil, and tadalafil, which may result in a more favorable side-effect profile. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：2365 / 2369

页数：5

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