دورية
Synthesis and Evaluation of 11β-Substituted 21-Chloro/Iodo-(17α,20E/Z)-19-norpregna-1,3,5(10),20-tetraene-3,17β-diols: High-Affinity Ligands for the Estrogen Receptor
| العنوان: | Synthesis and Evaluation of 11β-Substituted 21-Chloro/Iodo-(17α,20E/Z)-19-norpregna-1,3,5(10),20-tetraene-3,17β-diols: High-Affinity Ligands for the Estrogen Receptor |
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| المؤلفون: | Hanson, R. N., Napolitano, E., Fiaschi, R. |
| المصدر: | Journal of Medicinal Chemistry; November 19, 1998, Vol. 41 Issue: 24 p4686-4692, 7p |
| مستخلص: | We have synthesized six new estrogens substituted at the 11β-position with a methoxy or vinyl group and at the 17α-position with an (E)- or (Z)-chloro/iodovinyl moiety. The products were obtained in good overall yields from the corresponding tri-n-butylstannylvinyl intermediates using the electrophilic halodestannylation methodology. The six new ligands were compared to the 11β-unsubstituted chloro/iodovinyl derivatives and the 11β-methoxy (E)- and (Z)-iodovinyl estrogens to evaluate the effects of 11β-substitution and 20E/Z-stereochemistry. While all the compounds exhibited high affinity for the estrogen receptor, the 20Z-isomers demonstrated higher affinity than the corresponding 20E-isomers. In addition, the presence of the lipophilic 11β-substituent was favored over either no substituent or a polar (methoxy) group. Within each isomeric series, the presence of the 21-halo substituent had different effects. For the 20E-series, the 21-chloro products had a higher affinity than the 21-iodo analogue, whereas for the 20Z-series the effect was reversed. These results provide additional insights into the interaction of substituted estradiols with the hormone binding domain of the estrogen receptor. |
| قاعدة البيانات: | Supplemental Index |
Find this issue from the American Chemical Society | تدمد: | 00222623 15204804 |
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