OPIOID RECEPTOR LIGANDS

阿片受体配体

• 批准号: 3208786
• 负责人: Wendel L. Nelson
• 金额: $ 10.75万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-05-01 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3208786
• 关键词: analgesics; chemical synthesis; covalent bond; drug addiction antagonist; epoxides; ethylene oxide; isothiocyanates; lactones; mutagen testing; radiopharmacology; radiotracer; smooth muscle; tritium

The objective for this research project is the synthesis and preliminary evaluation of derivatives of opioid ligands derived from agents which interact with opioid receptor subtypes. It is anticipated that preparation and testing of these compounds will provide greater understanding of the structural requirements at opioid receptors, and may lead to further characterization of opioid receptor subtypes. Ligands which interact at Mu, Delta, Kappa, Sigma opioid receptor subtypes will be converted into compounds with covalent binding potential. Based on previous work with Alpha-methylene-Gamma-lactones, derived from naltrexone, this moiety will be incorporated. Additional potentially selective ligands which incorporate epoxide, glycidate ester, thiirane and isothiocyanate groups are proposed. Methods of incorporation of tritium into Alpha-methylene-Gamma-lactones are proposed. The compounds will be tested for analgesia and antagonism activity through the CPDD. In vitro work in opioid receptor preparations and smooth muscle (rat vas deferens and guinea pig ileum) will be arranged through the CPDD and with collaborators.

该研究项目的目的是综合和初步 评估来自药剂的阿片类药物配体的衍生物 与阿片受体亚型相互作用。 预计准备 这些化合物的测试将提供对 阿片受体的结构要求，可能会进一步 阿片受体亚型的表征。 在MU，Delta，Kappa，Sigma阿片受体亚型相互作用的配体 将转换为具有共价结合势的化合物。 基于 以前用α-甲基 - 伽马 - 内酯的工作，源自纳曲酮， 该部分将合并。 其他潜在的选择性配体 结合了环氧，糖化酯，硫烷和异硫氰酸酯 提出了组。 将tritium掺入的方法 提出了α-甲基 - γ-内酯。 这些化合物将通过 CPDD。 阿片受体制剂和平滑肌的体外工作 （大鼠VAS延期和豚鼠回肠）将通过CPDD排列 并与合作者。