Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1369195 | Bioorganic & Medicinal Chemistry Letters | 2013 | 5 Pages |
Abstract
We identified potent, selective PDE2 inhibitors by optimizing residual PDE2 activity in a series of PDE4 inhibitors, while simultaneously minimizing PDE4 activity. These newly designed PDE2 inhibitors bind to the PDE2 enzyme in a cGMP-like mode in contrast to the cAMP-like binding mode found in PDE4. Structure activity relationship studies coupled with an inhibitor bound crystal structure in the active site of the catalytic domain of PDE2 identified structural features required to minimize PDE4 inhibition while simultaneously maximizing PDE2 inhibition.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Mark S. Plummer, Joseph Cornicelli, Howard Roark, Donald J. Skalitzky, Charles J. Stankovic, Susan Bove, Jayvardhan Pandit, Annise Goodman, James Hicks, Aurash Shahripour, David Beidler, Xiao Kang Lu, Brian Sanchez, Christopher Whitehead, Ron Sarver,