BIOLOGICALLY ACTIVE STEROID ANALOGS

描述：(改编自《调查者摘要》)：目标1是合成 ~(18)F-雄激素正电子发射断层显像 前列腺癌。类固醇包括一种活性雄激素和前激素。 它们受到新陈代谢的保护，以最大限度地发挥生物信号。这些 用18F标记C-7Alpha的类固醇将被合成并进行测试 雄激素受体在大鼠和兔前列腺中的浓度。 目标2合成18F和123I标记的吡啶和N-取代的嘧啶 基于活性糖皮质激素的吡唑类固醇，可维拉唑。这些 类固醇，其杂环中含有N-活化的离开基团 系统，是专门为同位素交换反应设计的。类固醇 用作PET或单光子发射断层扫描(SPECT)试剂 成像大脑中糖皮质激素受体丰富的区域，即海马体。 目标3是合成和测试雌二醇的类似物，这些类似物是有效的雌激素，但 酶不稳定，导致它们迅速转化为非活性 代谢物。它们被设计成用作当地的雌激素。

DESCRIPTION: (Adapted from the Investigator's Abstract): Aim 1 is to synthesize 18F-labeled androgens for Positron Emission Tomography (PET) imaging of prostate cancer. The steroids include an active androgen as well as prohormones that are metabolically protected to maximize the biological signal. These steroids, labeled at C-7alpha with 18F, will be synthesized and tested for androgen receptor mediated concentration in the prostate of rats and rabbits. Aim 2 is to synthesize 18F and 123I labeled pyridyl and pyrimidyl N-substituted pyrazolo steroids based on the active glucorcorticoid, cortivazol. These steroids, containing N-activated leaving groups in their heterocyclic ring system, are designed specifically for isotope exchange reactions. The steroids are intended as PET or Single Photon Emission Tomography (SPECT) agents for imaging the glucocorticoid receptor rich region of the brain, the hippocampus. Aim 3 is to synthesize and test analogs of E2 that are potent estrogens and yet enzymatically labile which cause them to be converted rapidly into inactive metabolites. They are designed for use as local estrogens.