METABOTROPIC RECEPTOR LIGANDS

描述：本研究提案的目标是开发 针对各种亚型的选择性和有效的激动剂和拮抗剂 代谢型谷氨酸受体。 为此，以下潜力 将合成配体： (1) 构象约束类似物 L-AP4以开发选择性激动剂； (2) 甲基-类似物 L-AP4探索其拮抗剂能力背后的基础； (3) 使君子酸类似物，其中恶二唑烷二酮环为 被不同的其他杂环系统取代生成 mGluR1和mGluR5受体的选择性激动剂或拮抗剂； (4) 君子兰酸的构象受限类似物 各种构象。 这些化合物将被评估其 在特定的克隆和拮抗剂中充当激动剂和拮抗剂的能力 表达代谢型受体。 这项研究的目的是要取得成果 激动剂和拮抗剂的发现和开发 已发现的代谢型受体的各种亚型。

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.