11-(pyridinylphenyl)steroids--a new class of mixed-profile progesterone agonists/antagonists.
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.
Rewinkel
Jos
J
Department of Medicinal Chemistry, NV Organon, PO Box 20, 5340 BH Oss, The Netherlands. jos.rewinkel@organon.com
Enthoven
Mark
M
Golstein
Irene
I
van der Rijst
Marcel
M
Scholten
André
A
van Tilborg
Martin
M
de Weys
Dirk
D
Wisse
Jeffry
J
Hamersma
Hans
H
D008024:Ligands; D011278:Pregnanes / Q000737:chemistry; D011374:Progesterone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry*; D011980:Receptors, Progesterone; D013256:Steroids / Q000737:chemistry*; D013329:Structure-Activity Relationship
D008024:Ligands; D011278:Pregnanes; D011980:Receptors, Progesterone; D013256:Steroids; D011374:Progesterone