Novel pyrrole-containing progesterone receptor modulators
| Autor: | Andrew Fensome, Lori E. Miller, Jay Wrobel, Valerie Hudak, Reinhold R. W. Bender, Puwen Zhang, Jeffrey I. Cohen, Mark A. Collins, Zhiming Zhang, Richard C. Winneker, Rayomond J. Unwalla, Yuan Zhu |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
chemistry.chemical_classification
Indoles Nitrile Stereochemistry Organic Chemistry Clinical Biochemistry Nitro compound Pharmaceutical Science Biochemistry Chemical synthesis In vitro Benzoxazines chemistry.chemical_compound chemistry Drug Discovery Progesterone receptor Lactam Molecular Medicine Moiety Pyrroles Receptors Progesterone Molecular Biology Pyrrole |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 14:2185-2189 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2004.02.054 |
| Popis: | A series of 1,4-dihydro-2H-[d][3,1]-benzoxazin-2-one and 1,3-dihydro-[3H]-indol-2-one containing 6- or 5-, respectively, appended substituted pyrrole moieties were synthesized and evaluated for their ability to modulate the activity of the progesterone receptor (PR). Key structural changes to the pyrrole moieties of these molecules were shown to have a predictive influence as to whether the compounds behaved as PR agonists or antagonists. Compounds with the 5(')-cyano-2(')-pyrrole moiety (e.g., 32, 33, and 38) were shown to be potent PR agonists (EC(50)'s of 1.1, 1.8, and 2.8 nM, respectively). Compounds with the 5(')-nitro-2(')-pyrrole moiety (e.g., 34 and 36) were shown to be PR antagonists (IC(50)'s of 180 and 36 nM, respectively). |
| Databáze: | OpenAIRE |
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