کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1363352 | 981510 | 2010 | 6 صفحه PDF | دانلود رایگان |
Here we describe the SAR of a series of potent and selective mPGES-1 inhibitors based on an oxicam template. Compound 13j demonstrated low nanomolar mPGES-1 inhibition in an enzyme assay. In addition, it displayed PGE2 inhibition in a cell-based assay (0.42 μM) and had over 238-fold selectivity for mPGES-1 over COX-2 and over 200-fold selectivity for mPGES-1 over 6-keto PGF1α.
The design and synthesis of a series of potent and selective mPGES-1 inhibitors based on an oxicam template are described. Our SAR studies allowed us to optimize this series resulting in the identification of compound 13j which demonstrated potent inhibition in both enzyme and cellular assay. This series of compounds illustrated good mPGES-1 inhibition along with good selectivity over COX-2 and 6-keto PGF1α.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 20, Issue 5, 1 March 2010, Pages 1604–1609