Skaddan M B, Katzenellenbogen J A
Department of Chemistry, University of Illinois, 600 S. Mathews Avenue, Urbana, Illinois 61801, USA.
Bioconjug Chem. 1999 Jan-Feb;10(1):119-29. doi: 10.1021/bc980094q.
The diagnosis and staging of breast cancer could be improved by the development of imaging radiopharmaceuticals that provide a noninvasive determination of the estrogen receptor (ER) status of tumor cells. Toward this goal, we have synthesized a number of integrated "3+1" oxorhenium(V) complexes designed to mimic estradiol and a class of nonsteroidal estrogens, the tetrahydrochrysenes (THC). The monodentate component of the estradiol mimic is a p-hydroxyphenethyl thiol ligand with ethyl substituents at the benzylic and homobenzylic positions. Model complexes of this ligand were easily made, but steric hindrance of the secondary thiol prevented the formation of the complex with the disubstituted ligand. The three "3+1" oxorhenium(V) complexes prepared to mimic the THC class mimics represent the first pyridinedithiol rhenium complexes of their kind to be made. These complexes are quite stable to air and moisture. The target tridentate ligand was prepared from chelidamic acid, and the VT NMR of the rhenium complex displays interesting fluxional behavior. The binding affinities of these complexes for the estrogen receptor are low, and their lipophilicities are rather high. Nevertheless, our findings provide a further refinement of our understanding of ligand structure-binding affinity correlations for the estrogen receptor.
开发能够对肿瘤细胞雌激素受体（ER）状态进行无创测定的放射性核素显像剂，有望改善乳腺癌的诊断和分期。为实现这一目标，我们合成了一系列旨在模拟雌二醇和一类非甾体雌激素——四氢并四苯（THC）的整合型“3 + 1”铼（V）氧配合物。雌二醇模拟物的单齿成分是一种对羟基苯乙硫醇配体，在苄基和高苄基位置带有乙基取代基。这种配体的模型配合物很容易制备，但仲硫醇的空间位阻阻止了与二取代配体形成配合物。为模拟THC类化合物而制备的三种“3 + 1”铼（V）氧配合物是此类吡啶二硫醇铼配合物中的首例。这些配合物对空气和水分相当稳定。目标三齿配体由螯合酸制备，铼配合物的变温核磁共振显示出有趣的动态行为。这些配合物对雌激素受体的结合亲和力较低，亲脂性较高。尽管如此，我们的研究结果进一步完善了我们对雌激素受体配体结构 - 结合亲和力相关性的理解。
