METABOTROPIC RECEPTOR LIGANDS

描述：本研究提案的目标是开发 的选择性和有效的激动剂和拮抗剂的各种亚型， 代谢型谷氨酸受体 为此，以下潜力 配体将被合成：（1）构象受限的类似物 的L-AP 4，以开发选择性激动剂;（2）甲基- 探索L-AP 4作为拮抗剂的能力背后的基础; (3)其中恶二唑烷二酮环为 被不同的其他杂环系统取代， mGluR 1和mGluR 5受体的选择性激动剂或拮抗剂; 和（4）使君子酸的构象限制类似物， 各种构象。 将评估这些化合物的 作为特异性克隆和受体激动剂和拮抗剂的能力， 表达代谢型受体。 这项研究旨在 在发现和开发用于抗肿瘤的激动剂和拮抗剂方面， 已经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.