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Synthesis and biological activity of novel nonsteroidal progesterone receptor antagonists based on cyclocymopol monomethyl ether.
Hamann, L G; Farmer, L J; Johnson, M G; Bender, S L; Mais, D E; Wang, M W; Crombie, D; Goldman, M E; Jones, T K.
Afiliación
  • Hamann LG; Department of Endocrine Chemistry Research, Ligand Pharmaceuticals, Inc., San Diego, California 92121, USA.
J Med Chem ; 39(9): 1778-89, 1996 Apr 26.
Article en En | MEDLINE | ID: mdl-8627601
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.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Progesterona / Ciclohexanos / Anisoles Límite: Animals / Female / Humans / Male Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 1996 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Progesterona / Ciclohexanos / Anisoles Límite: Animals / Female / Humans / Male Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 1996 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos