METABOTROPIC RECEPTOR LIGANDS

代谢受体配体

• 批准号: 2431314
• 负责人: RODNEY L JOHNSON
• 金额: $ 21.62万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-22 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2431314
• 关键词: aminoacid analog; chemical synthesis; conformation; electrophysiology; excitatory aminoacid; glutamate receptor; neuropharmacology; neurotransmitter agonist; neurotransmitter antagonist; receptor binding; receptor sensitivity; stereochemistry; tissue /cell culture

DESCRIPTION: The objective of this research proposal is the development of selective and potent agonists and antagonists for various subtypes of metabotropic glutamate receptors. To this end, the following potential ligands will be synthesized: (1) Conformationally constrained analogs of L-AP4 in order to develop selective agonists; (2) analogs of methyl- L-AP4 to explore the basis behind its ability to serve as antagonist; (3) Analogs of quisqualic acid in which the oxadiazolidinedione ring is replaced with different other heterocyclic ring systems to generate selective agonists or antagonists of the mGluR1 and mGluR5 receptors; and (4) Conformationally constrained analogs of quisqualic acid in various conformations. These compounds will be evaluated for their ability to serve as agonists and antagonists at specific cloned and expressed metabotropic receptors. This research is intended to result in the discovery and development of agonists and antagonists for the various subtypes of metabotropic receptors that have been discovered.

描述：该研究建议的目的是发展 各种亚型的选择性和有效激动剂和拮抗剂 代谢性谷氨酸受体。 为此，以下潜力 配体将合成：（1）构象约束类似物 L-ap4的of l-ap4以发展选择性激动剂； （2）甲基的类似物 L-AP4探索其作为对手的能力背后的基础； （3）黄质酸的类似物的类似物，其中oxadiazolidedione环为 替换为其他其他杂环环系统生成 MGLUR1和MGLUR5受体的选择性激动剂或拮抗剂； （4）Quisqualic Acid构象约束类似物中的类似物 各种构象。 这些化合物将被评估 在特定克隆和 表达的代谢受体。 这项研究旨在结果 在发现和发展激动剂和对手 已经发现的各种代谢受体的亚型。