title: 11-(pyridinylphenyl)steroids--a new class of mixed-profile progesterone agonists/antagonists.
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.
authors.affiliation: Department of Medicinal Chemistry, NV Organon, PO Box 20, 5340 BH Oss, The Netherlands. jos.rewinkel@organon.com
authors.forename: Jos
authors.initials: J
authors.lastname: Rewinkel
authors.forename: Mark
authors.initials: M
authors.lastname: Enthoven
authors.forename: Irene
authors.initials: I
authors.lastname: Golstein
authors.forename: Marcel
authors.initials: M
authors.lastname: van der Rijst
authors.forename: André
authors.initials: A
authors.lastname: Scholten
authors.forename: Martin
authors.initials: M
authors.lastname: van Tilborg
authors.forename: Dirk
authors.initials: D
authors.lastname: de Weys
authors.forename: Jeffry
authors.initials: J
authors.lastname: Wisse
authors.forename: Hans
authors.initials: H
authors.lastname: Hamersma
mesh_terms: 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
chemical_list: D008024:Ligands; D011278:Pregnanes; D011980:Receptors, Progesterone; D013256:Steroids; D011374:Progesterone