Identification of iminooxothiazolidines as secreted frizzled related protein-1 inhibitors

Identification of iminooxothiazolidines as secreted frizzled related protein-1 inhibitors and the SAR requirements are reported. Secreted frizzled related protein-1 (sFRP-1) inhibitors have the potential to be used for the treatment of osteoporosis or other bone related disorders, since the level of sFRP-1 affects osteoblast apoptosis and proliferation. From high throughput screening, we have identified a class of iminooxothiazolidines as sFRP-1 inhibitors. Structure–activity relationships were established for various regions of the scaffold along with the biochemical characterization of this class to probe selectivity, binding and ex vivo activity.