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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:19

Article

Owen, Dafydd R.²  Walker, John K.¹  Jacobsen, E. Jon¹  Freskos, John N.¹  Hughes, Robert O.¹  Brown, David L.¹  Bell, Andrew S.²  Brown, David G.²  Phillips, Christopher²  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. Joseph¹  Fox, David N. A.²  Palmer, Michael J.²  Ringer, Tracy²  Rodriquez-Lens, Margarita²  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, Alan³  Yu, Yung³ 

[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

关键词: PDE5;    PDE6;    PDE11;    Inhibitors;   

DOI  :  10.1016/j.bmcl.2009.06.012

来源: Elsevier

【 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.

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