posted on 1996-04-26, 00:00authored byLawrence G. Hamann, Luc J. Farmer, Michael G. Johnson, Steven L. Bender, Dale E. Mais, Ming-Wei Wang, Diane Crombie, Mark E. Goldman, Todd K. Jones
A novel class of nonsteroidal progesterone receptor antagonists
has been synthesized and was
shown to exhibit moderate binding affinity for hPR-A, the ability to
inhibit the transcriptional
activity of human progesterone receptor (hPR) in cell-based assays, and
anti-progestational
activity in a murine model. Cyclocymopol monomethyl ether, a
component of the marine alga
Cymopolia barbata was weakly active in random screening
against PR. Investigations into
the SAR surrounding the core of this natural product lead structure
resulted in improved in
vitro activity. In contrast to the cross-reactivity profiles
observed with known steroidal anti-progestins, compounds of the general structural class described display
a high degree of
selectivity for the progesterone receptor and no functional activity on
the glucocorticoid receptor.