Wallace Owen B, Bryant Henry U, Shetler Pamela K, Adrian Mary D, Geiser Andrew G
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Bioorg Med Chem Lett. 2004 Oct 18;14(20):5103-6. doi: 10.1016/j.bmcl.2004.07.072.
For selective estrogen receptor modulators (SERMs), the orientation of the basic side chain relative to the SERM core has a significant impact on function. The synthesis and biological evaluation of two series of SERMs are disclosed, where the ligand side chain is constrained to adopt a defined orientation. Compounds where the side chain is forced into the plane of the SERM core have a different profile compared to those compounds where the side chain is pseudo-orthogonal, particularly with regard to antagonism of estradiol action on an Ishikawa uterine cell line.
对于选择性雌激素受体调节剂（SERM），碱性侧链相对于SERM核心的取向对其功能有重大影响。本文披露了两个系列SERM的合成及生物学评估，其中配体侧链被限制为采用特定取向。与侧链呈准正交的化合物相比，侧链被迫处于SERM核心平面内的化合物具有不同的特性，尤其是在雌二醇对石川子宫细胞系作用的拮抗方面。
