کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1369195 | 981764 | 2013 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Discovery of potent, selective, bioavailable phosphodiesterase 2 (PDE2) inhibitors active in an osteoarthritis pain model, Part I: Transformation of selective pyrazolodiazepinone phosphodiesterase 4 (PDE4) inhibitors into selective PDE2 inhibitors
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موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
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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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 11, 1 June 2013, Pages 3438–3442
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 23, Issue 11, 1 June 2013, Pages 3438–3442
نویسندگان
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,