Napolitano E, Fiaschi R, Hanson R N
Section of Medicinal Chemistry, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, MA 02115.
J Steroid Biochem Mol Biol. 1990 Oct;37(2):295-300. doi: 10.1016/0960-0760(90)90341-h.
As part of an ongoing program to develop high affinity estrogenic ligands we have synthesized the 11 beta-vinyl, 11 beta-ethyl- and 1,11 beta-ethanoestradiols. Because the 1,11 beta-ethano-estradiol had not been previously reported in the literature, the investigation of its receptor binding characteristics would provide valuable insight into the effect of 1/11 beta-substitution. The data obtained in this study indicate that although significant estrogen receptor affinity is present for the 1,11 beta-ethano derivative, the RBA values, 5-22.4%, were far less than those observed (5-300-fold less) for the corresponding 11 beta-ethyl and 11 beta-vinyl estradiols and less than those for the 1-methyl and 11 beta-methyl estradiols. These results suggest that the orientation that the 11 beta-substituent must occupy is directed away from the A-ring and that substituents in the 1-11 pocket produce a detrimental effect on receptor interactions.
作为正在进行的开发高亲和力雌激素配体项目的一部分，我们合成了11β-乙烯基、11β-乙基和1,11β-亚乙基雌二醇。由于1,11β-亚乙基雌二醇此前未在文献中报道过，对其受体结合特性的研究将为1/11β取代的影响提供有价值的见解。本研究获得的数据表明，虽然1,11β-亚乙基衍生物具有显著的雌激素受体亲和力，但其相对结合活性（RBA）值为5-22.4%，远低于相应的11β-乙基和11β-乙烯基雌二醇（低5-300倍），也低于1-甲基和11β-甲基雌二醇。这些结果表明，11β取代基必须占据的方向是远离A环的，并且1-11口袋中的取代基会对受体相互作用产生不利影响。
