| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1378764 | Bioorganic & Medicinal Chemistry Letters | 2005 | 4 Pages |
A series of potent and selective inhibitors of the inducible microsomal PGE2 synthase (mPGES-1) has been developed based on the indole FLAP inhibitor MK-886. Compounds 23 and 30 inhibit mPGES-1 with potencies in the low nanomolar range and with selectivities of at least 100-fold compared to their inhibition of mPGES-2, thromboxane synthase and binding affinity to FLAP. They also block the production of PGE2 in cell based assays but with a decreased potency and more limited selectivity compared to the enzyme assays.
Graphical abstractThe in vitro potency and selectivity of a novel series of mPGES-1 inhibitors derived from MK-886 is described. SAR studies in this series led to the identification of inhibitors 23 and 30.Figure optionsDownload full-size imageDownload as PowerPoint slide
