11-(pyridinylphenyl)steroids--a new class of mixed-profile progesterone agonists/antagonists.

Article Details

Citation

Rewinkel J, Enthoven M, Golstein I, van der Rijst M, Scholten A, van Tilborg M, de Weys D, Wisse J, Hamersma H

11-(pyridinylphenyl)steroids--a new class of mixed-profile progesterone agonists/antagonists.

Bioorg Med Chem. 2008 Mar 15;16(6):2753-63. doi: 10.1016/j.bmc.2008.01.010. Epub 2008 Jan 11.

PubMed ID
18243712 [ View in PubMed
]
Abstract

Recently, a new class (often referred to as SPRMs: selective progesterone receptor modulators) of progesterone receptor ligands with mixed agonist/antagonist properties has been described. Such compounds are envisaged, for example, as treatment for endometriosis, uterine fibroids, and leiomyomas. Existing SPRMs include Asoprisnil 1 and Uliprisnil acetate 2. In our hands, however, these compounds proved to have a predominantly or exclusively antagonistic in vitro profile, which may make this type of compound less attractive, for example, as contraceptives. We therefore aimed at a class of mixed-profile compounds that would show a more evenly balanced agonist/antagonist profile. A novel class of 11beta-[4-(heteroaryl)phenyl]-substituted pregnanes was identified that displayed the desired balance. Contrary to known SPRMs, this novel class of MPP (mixed-profile progestagen) was found to have a truly mixed activity, including a sizeable agonist component.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
UlipristalProgesterone receptorEC 50 (nM)>100N/AN/ADetails
UlipristalProgesterone receptorIC 50 (nM)0.2N/AN/ADetails