Synthesis and biological activity of novel nonsteroidal progesterone receptor antagonists based on cyclocymopol monomethyl ether.
Article Details
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Hamann LG, Farmer LJ, Johnson MG, Bender SL, Mais DE, Wang MW, Crombie D, Goldman ME, Jones TK
Synthesis and biological activity of novel nonsteroidal progesterone receptor antagonists based on cyclocymopol monomethyl ether.
J Med Chem. 1996 Apr 26;39(9):1778-89.
- PubMed ID
- 8627601 [ View in PubMed]
- Abstract
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 antiprogestins, 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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Dexamethasone Glucocorticoid receptor Ki (nM) 5.5 N/A N/A Details Mifepristone Glucocorticoid receptor Ki (nM) 0.68 N/A N/A Details Mifepristone Glucocorticoid receptor IC 50 (nM) 0.8 N/A N/A Details Mifepristone Progesterone receptor IC 50 (nM) 0.18 N/A N/A Details Mifepristone Progesterone receptor Ki (nM) 0.58 N/A N/A Details Mifepristone Progesterone receptor IC 50 (nM) 0.35 N/A N/A Details Progesterone Androgen receptor IC 50 (nM) 37 N/A N/A Details Progesterone Androgen receptor Ki (nM) 8.5 N/A N/A Details Progesterone Glucocorticoid receptor IC 50 (nM) >1000 N/A N/A Details Progesterone Glucocorticoid receptor Ki (nM) 31 N/A N/A Details Progesterone Mineralocorticoid receptor IC 50 (nM) >14 N/A N/A Details Progesterone Progesterone receptor Ki (nM) 3.5 N/A N/A Details