Identification, synthesis and SAR of amino substituted pyrido[3,2b]pyrazinones as potent and selective PDE5 inhibitors

被引：19

作者：

Owen, Dafydd R. ^{[2
]}

Walker, John K. ^{[1
]}

Jacobsen, E. Jon ^{[1
]}

Freskos, John N. ^{[1
]}

Hughes, Robert O. ^{[1
]}

Brown, David L. ^{[1
]}

Bell, Andrew S. ^{[2
]}

Brown, David G. ^{[2
]}

Phillips, Christopher ^{[2
]}

Mischke, Brent V. ^{[1
]}

Molyneaux, John M. ^{[1
]}

Fobian, Yvette M. ^{[1
]}

Heasley, Steve E. ^{[1
]}

Moon, Joseph B. ^{[1
]}

Stallings, William C. ^{[1
]}

Rogier, D. Joseph ^{[1
]}

Fox, David N. A. ^{[2
]}

Palmer, Michael J. ^{[2
]}

Ringer, Tracy ^{[2
]}

Rodriquez-Lens, Margarita ^{[2
]}

Cubbage, Jerry W. ^{[1
]}

Blevis-Bal, Radhika M. ^{[1
]}

Benson, Alan G. ^{[1
]}

Acker, Brad A. ^{[1
]}

Maddux, Todd M. ^{[1
]}

Tollefson, Michael B. ^{[1
]}

Bond, Brian R. ^{[3
]}

MacInnes, Alan ^{[3
]}

Yu, Yung ^{[3
]}

机构：

[1] Pfizer Global Res & Dev, Dept Chem, St Louis, MO 63017 USA

[2] Pfizer Global Res & Dev, Dept Chem, Sandwich CT13 9NJ, Kent, England

[3] Pfizer Global Res & Dev, Dept Biol, St Louis, MO 63017 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 15期

关键词：

PDE5; PDE6; PDE11; Inhibitors; SILDENAFIL;

D O I：

10.1016/j.bmcl.2009.06.012

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new class of potent and selective PDE5 inhibitors is disclosed. Guided by X-ray crystallographic data, optimization of an HTS lead led to the discovery of a series of 2-aryl, (N8)-alkyl substituted-6-aminosubstituted pyrido[3,2b]pyrazinones which show potent inhibition of the PDE5 enzyme. Synthetic details and some structure-activity relationships are also presented. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：4088 / 4091

页数：4

共 11 条

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