RESOLUTION & ANTITUMOR TESTING OF CHIRAL ANTIESTROGENS

这项研究的目的是准备和评估一个新的班级 非类固醇类抗雌激素，优于目前用于 乳腺癌的治疗。目前，还没有可用的抗雌激素。 它们缺乏雌激素(促子宫)活性。数据显示在 这一建议表明，先导化合物，类似物II，缺乏 在小鼠子宫中的促子宫活性，这不同于其他抗雌激素 存在。类似物II已经被发现要么同样有效，要么更有效 比他莫昔芬(一种临床上使用的促子宫的抗雌激素)有效 活动)在治疗已建立的肿瘤和预防 7，12-二甲基苯并[7，12-二甲基苯并()菲](DMBA)诱发的大鼠肿瘤形成 乳腺肿瘤模型。基于对Analog II和Steric的这些发现 在现有的抗雌激素中，一类新的抗雌激素是 建议。因此，这些新的类似物，一旦准备好，将被 准备好的，将在检测系统中检测其雌激素活性， 抗雌激素及其对体内促性腺激素分泌和受体的影响 体外结合活性。所有化合物将在未来一段时间内进行进一步评估 评价人乳腺癌细胞株MCF-7的抗肿瘤活性。主动型 这类缺乏雌激素激动剂的新型抗雌激素的成员 在人类中的活动将显著改善治疗 乳腺癌患者中的雌激素依赖性肿瘤。还有，那些 副作用很小的化合物在预防方面是有用的。 在预防妇女雌激素依赖性肿瘤发生中的作用 高风险类别。

The purpose of this study is to prepare and evaluate a new class of nonsteroidal antiestrogens which are superior to those currently used in the treatment of breast cancer. Presently, no antiestrogens are available which are devoid of estrogenic (uterotropic) activity. Data presented in this proposal indicate that a lead compound, Analog II, is devoid of uterotropic activity in mouse uteri, which is unlike other antiestrogens in existence. Analog II has been found to be either as effective or more effective than tamoxifen (a clinically used antiestrogen with uterotropic activity) in the treatment of established tumors and the prevention of tumorigenesis in the 7,12-dimethylbenz( )anthracene (DMBA)-induced rat mammary tumor model. Based on these findings with Analog II and the steric features in existing antiestrogens, a new class of antiestrogens is proposed. Consequently, these new analogs, when prepared, will be prepared, will be examined in assay systems for their estrogenic, antiestrogenic and effect on gonadotropin secretion in vivo and receptor binding activity in vitro. All compounds will be evaluated further in a MCF-7 human breast cancer cell line to assess antitumor activity. Active members of this novel class of antiestrogens which lack estrogen agonist activity in humans would significantly improve the treatment of estrogen-dependent tumors in patients with breast cancer. Also, those compounds which have very few side effects would be useful prophylactically in preventing the genesis of estrogen-dependent tumors in women who are in the high risk category.