The Development of Novel Annelation Reactions with Indolidene Intermediates

茚满中间体新型退火反应的进展

• 批准号: 1361260
• 负责人: Ken Feldman
• 金额: $ 45万
• 依托单位: Pennsylvania State Univ University Park
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1361260&HistoricalAwards=false
• 关键词: Development; Novel; Annelation; Reactions; Indolidene

Professor Ken Feldman of The Pennsylvania State University is developing efficient methods to prepare human hormone receptor binding agents to serve as potential drug candidates. This project is funded by the Chemical Synthesis program of the Chemistry Division at the National Science Foundation. These methods are based upon preliminary discoveries in Dr. Feldman's laboratory involving new approaches to stitch together small pieces of molecules in order to form larger chemical structures with control over molecular shape. These product molecules will aid in understanding the structural features that contribute to selective association with one hormone receptor over another. The funded research also includes studies on marine water remediation techniques, and the broader impacts of this latter work might include improvements in the quality of husbandry for marine ornamentals. The chemistry features a new approach to forming indolidenes, reactive indole-derived species that engage in bond formation to append either five-membered rings or seven-membered rings onto the indole framework. Since indoles with appended rings constitute important targets for drug discovery, this chemistry may impact several areas of pharmaceutical science. More specifically, preliminary reports ascribe a remarkable selectivity for activating the human progesterone receptor over other hormone receptors by a five-membered ring appended indole called lecanindole D, a naturally occurring fungal-derived material. The investigation of the structural basis for this selectivity is a major thrust of the funded research.

宾夕法尼亚州立大学的肯·费尔德曼教授正在开发有效的方法来制备人类激素受体结合剂，以作为潜在的候选药物。 该项目由美国国家科学基金会化学部的化学合成计划资助。 这些方法是基于费尔德曼博士实验室的初步发现，涉及将小分子拼接在一起的新方法，以形成更大的化学结构，并控制分子形状。 这些产物分子将有助于理解有助于与一种激素受体选择性结合的结构特征。受资助的研究还包括关于海水补救技术的研究，后一项工作的更广泛影响可能包括提高海洋生物的饲养质量。该化学的特点是一种新的方法来形成吲哚，反应性吲哚衍生的物种，从事键形成附加到吲哚框架上的五元环或七元环。 由于具有附加环的吲哚构成药物发现的重要靶点，这种化学可能会影响制药科学的几个领域。 更具体地说，初步报告归因于一个显着的选择性激活人孕酮受体超过其他激素受体的五元环附加吲哚称为lecanindole D，一种天然存在的真菌衍生的材料。 对这种选择性的结构基础的调查是资助研究的主要推动力。