CORE--DRUG SYNTHESIS

核心--药物合成

• 批准号: 7796647
• 负责人: DOUGLAS F. COVEY
• 金额: $ 13.74万
• 依托单位: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
• 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/7796647
• 关键词: Address; Alzheimer' s Disease; Antioxidants; Ensure; Estradiol; Goals; Grant; Laboratories; Methods; Modification; Neuroprotective Agents; Pharmaceutical Preparations; Preparation; Property; Reporting; Role; Series; Side; Steroids; Structure; Time; Universities; Washington; anabaseine; drug synthesis; hydroxyl group; neuroprotection; novel; programs

The Drug Synthesis Core will be established to support activities of Projects by Simpkins, Meyer, and Koulen in the Program. The role of the core for the progress of these projects is summarized in the following aims. Specific Aim 1. Synthesis of optimized antioxidant phenolic steroids for Project by Simpkins. Structure-activity studies carried out by us previously have indicated structural modifications that can be made to 17beta-estradiol that greatly enhance the neuroprotective potency of this steroid while at the same time decreasing or eliminating the compound's feminizing properties. The core will develop new synthetic methods that will provide additional compounds optimized for both neuroprotection and absence of feminizing actions. This core will also carry out the preparation of additional amounts of previously studied compounds. The continued availability of these compounds is essential for the mechanistic studies described in Project by Simpkins. Specific Aim 2. Synthesis of anabaseine compounds for Project by Meyer. Two specific aims in Project by Meyer require the availability of five different anabaseine derivatives. To ensure that supplies of these compounds remain available for study, the synthesis core will prepare additional supplies of these compounds. Previously reported synthetic methods will be used for preparation of the compounds. Specific Aim 3. Synthesis of modified NAEs for Project by Koulen. The facilities of the synthesis core will be utilized to undertake the preparation of a series of non-naturally occurring NAEs. The goal of preparing the new compounds is to extend the structure-activity studies undertaken in Project by Koulen.

该计划中将建立毒品合成核心，以支持Simpkins，Meyer和Koulen的项目。以下目的总结了核心在这些项目进步方面的作用。特定目的1。辛普金斯（Simpkins）为项目的优化抗氧化剂类固醇合成。我们先前进行的结构活性研究表明，可以对17beta-雌二醇进行结构修饰，从而大大提高了该类固醇的神经保护效力，同时降低或消除了该化合物的女性化特性。核心将开发新的合成方法 提供对神经保护作用和不存在女性化作用的其他化合物。该核心还将进行其他数量先前研究的化合物的准备。这些化合物的持续可用性对于Simpkins项目中描述的机械研究至关重要。特定目的2。迈耶（Meyer）为Project的Anabaseine化合物的合成。迈耶（Meyer）在项目中的两个具体目标要求五个不同的阶数衍生物的可用性。为了确保这些化合物的供应仍可用于研究，合成核心将准备这些化合物的其他供应。之前 报告的合成方法将用于制备化合物。特定目的3。库伦（Koulen）综合修改后的NAE。合成核心的设施将是 用于进行一系列非天然发生的NA的准备。准备新化合物的目的是扩展库伦（Koulen）在项目中进行的结构活性研究。