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：本研究方案的目标是发展 针对不同亚型的选择性和有效的激动剂和拮抗剂 代谢性谷氨酸受体。为此，有以下潜力 配体将被合成：(1)构象受限类似物 以开发选择性激动剂；(2)甲基-AP4类似物 L-AP4探讨其作为拮抗剂能力背后的基础； (3)其中恶二唑二酮环为的拟奎宁酸的类似物 用不同的其他杂环体系取代生成 MGluR1和mGluR5受体的选择性激动剂或拮抗剂； 和(4)构象受限的准奎奎酸类似物 不同的构象。这些化合物将被评估为它们的 能够作为激动剂和拮抗剂在特定的克隆和 表达的代谢性受体。这项研究的目的是为了 在发现和开发血管紧张素转换酶激动剂和拮抗剂 已发现的代谢性受体的各种亚型。