MEDICINAL CHEMISTRY APPLIED TO PROBLEMS PROMINENT IN SENESCENCE

药物化学应用于解决衰老中的突出问题

• 批准号: 3821412
• 负责人: J PITHA
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3821412
• 关键词: androgens; antiadrenergic agents; beta antiadrenergic agent; chemical binding; drug adverse effect; drug design /synthesis /production; drug metabolism; drug screening /evaluation; drug vehicle; human subject; lipid solubility; nutrition related tag; peripheral nervous system; prazosin; retinoids; testosterone; water solubility

Alkylating prazosin, a compound which was prepared in the Section last year and which has the potential to bind permanently to adrenergic receptors of the alpha1 type, was presently evaluated. This compound was found to bind reversibly to all receptors of this type but permanent binding was established only to a fraction of them. The results show that alpha1- adrenoceptors are not a homogenous group and division of these into subgroups will be necessary. A carbostyril derivative which fully activated and permanently binds to beta-adrenoceptors was designed and synthesized. This compound pulls the trigger of receptors, which are in charge of the "fight or flight" reaction, and keeps the trigger pulled down for the duration. Work at the University of Florida established the correctness of the design. When beta-adrenoceptors were activated by this compound they could not be deactivated by the addition of a beta-blocker, a deactivation which occurred when natural, reversibly acting hormones were used for the activation. Testosterone in the circulation of mammals rises several fold above its background levels during episodes lasting a couple of hours and occurring daily. By administration of the water soluble pharmaceutical form of testosterone, developed in the Section, these episodes may be imitated. Researchers at the University of Missouri used this preparation to establish the importance of testosterone episodes for androgen-sensitive behavior and physiology.

烷基化哌唑嗪是一种在以下方法中制备的化合物 去年的部分，有可能永久具有约束力 α1 型肾上腺素能受体，目前 评价。 发现该化合物可逆地结合到所有 这种类型的受体，但仅建立永久结合 他们中的一小部分。 结果表明，α1- 肾上腺素受体不是一个同质的群体并且它们的划分 分成子组是必要的。 一种完全活化且永久的喹诺酮衍生物 设计并合成了与β-肾上腺素受体结合的化合物。 这 化合物拉动受体的扳机，受体负责 “战斗或逃跑”反应，并扣动扳机 持续时间。 在佛罗里达大学工作成立 设计的正确性。 当β-肾上腺素能受体 被这种化合物激活，它们不能被 添加β-受体阻滞剂，失活发生在 使用天然的、可逆作用的激素来激活。 哺乳动物循环中的睾丸激素增加数倍 在持续数次的事件中高于其背景水平 小时并每天发生。 通过施用水溶性 该科开发的睾酮药物形式， 这些情节可能会被模仿。 大学的研究人员 密苏里州利用这种准备工作来确定 雄激素敏感行为的睾酮发作和 生理。