ANTIANDROGENS--CONTROL OF BENIGN PROSTATIC HYPERPLASIA

这项研究的目的是开发新的类固醇 用于控制良性前列腺增生的抗雄激素药物 （BPH）。 这些新的药物也可能对前列腺的控制有价值。 癌症和其他雄激素依赖性内分泌失调。 在以前的工作中 我们发现了几种有趣的生物先导化合物， 抗雄激素的研究，并已开发出化学方法， 合成. 此外，我们还对已知的 抗雄激素 因此，我们认为，我们完全有资格进行 要求的研究。 我们提出了一个研究计划， 新的抗雄激素，1）可以干扰的作用， 5 α-双氢睾酮（DHT）在前列腺中的竞争， 细胞质雄激素受体，2）缺乏其他激素活性 这可能会导致麻烦和不必要的副作用，3）结合弱 前列腺对血清蛋白质的选择性摄取， 循环睾酮和双氢睾酮 这些研究应该提供更好的 理解，并提供新的见解，结构-活性 受体水平上体外抗雄激素活性的关系 和体内雄激素敏感器官中。 新的化合物，建议将进行细胞质结合试验 对大鼠雄激素、雌激素和孕酮受体的亲和力，或 兔，用于与大鼠中的雄激素结合蛋白（ABP）结合，用于 大鼠中的抗雄激素活性，以及 适当的动物模型。

The objective of the proposed research is to develop new steroid antiandrogenic agents for the control of Benign Prostatic Hyperplasia (BPH). These new agents may also be of value for the control of prostate cancer and other androgen-dependent endocrine disorders. In previous work we have uncovered several interesting biological lead compounds for antiandrogenic studies and have developed chemical methodology for their synthesis. Also, we have done a comprehensive literature survey of known antiandrogens. Therefore, we believe that we are well qualified to conduct the requested research. We propose a research plan for the development of new antiandrogens that 1) could interfere with the action of 5Alpha-dihydrotestosterone (DHT) in the prostate by competing for the cytoplasmic androgen receptor, 2) are devoid of other hormonal activity that could lead to bothersome and unwanted side effects, and 3) bind weakly to serum proteins and show selective uptake by the prostate over circulating testosterone and DHT. These studies should provide a better understanding of, and afford new insights into, structure-activity relationships for antiandrogenic activity in vitro at the receptor level and in vivo in androgen-sensitive organs. The new compounds that are proposed will be assayed for cytosol binding affinity for androgen, estrogen, and progestin receptors in rats or rabbits, for binding to androgen binding protein (ABP) in rats, for antiandrogenic activity in rats, and for other hormonal activity in the appropriate animal model as warranted.