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[Synthesis of triphenylethylene with aliphatic cyclic moiety and its antagonism on estrogen receptor]
1Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Department of Synthetic Medicinal Chemistry, Beijing 100050, China.
Aim:
In order to improve the biological activity and reduce the side effects and toxicity, a series of novel estrogen receptor antagonists were designed.
Methods:
The key triphenylethylene intermediates were obtained by the McMurry reaction. The target compounds were prepared by etherification. The binding affinities of the target compounds for the estrogen receptor in rat uterine cytosol were measured by a competitive binding assay and their estrogen agonistic/antagonistic properties were investigated in the 3-day uterine weight assay in the immature rats.
Results:
Thirty-five new compounds have been synthesized and their geometric configuration were determined by X-ray crystallography and 1HNMR spectral data.
Conclusion:
All of the test compounds showed affinity for the estrogen receptor (IC50 < 10(-6) mol.L-1), especially compound 35 with IC50 1.07 x 10(-8) mol.L-1. Some compounds are antagonists, inhibiting uterus growth; others are agonists, promoting uterus growth. Compounds 14 and 27 are superior antagonists to tamoxifen.