SYNTHESIS AND BIOLOGICAL-ACTIVITY OF NOVEL NONSTEROIDAL PROGESTERONE-RECEPTOR ANTAGONISTS BASED OIL CYCLOCYMOPOL MONOMETHYL ETHER

A novel class of nonsteroidal progesterone receptor antagonists has be en synthesized and was shown to exhibit moderate binding affinity for hPR-A, the ability to inhibit the transcriptional activity of human pr ogesterone receptor (hPR) in cell-based assays, and anti-progestationa l activity in a murine model. Cyclocymopol monomethyl ether, a compone nt of the marine alga Cymopolia barbata was weakly active in random sc reening against PR. Investigations into the SAR surrounding the core o f this natural product lead structure resulted in improved in vitro ac tivity. In contrast to the cross-reactivity profiles observed with kno wn steroidal anti-progestins, compounds of the general structural clas s described display a high degree of selectivity for the progesterone receptor and no functional activity on the glucocorticoid receptor.