Structure-Activity of Opioid Drugs

阿片类药物的结构-活性

• 批准号: 7966895
• 负责人: Richard Rothman
• 金额: $ 60.13万
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7966895
• 关键词: Absence of pain sensation; Affinity; Agonist; Analgesics; Antidepressive Agents; Area; Behavior; Behavioral; Binding; Cocaine; Data; Dependence; Development; Diterpenes; Dopamine; Endorphins; Furans; Heroin; Human; In Vitro; Isomerism; Ligands; Mediating; Modeling; Morphine; Narcotic Abuses; Narcotic Antagonists; Narcotics; Nucleus Accumbens; Opioid; Opioid Peptide; Opioid Receptor; Oxides; Pharmaceutical Chemistry; Pharmaceutical Preparations; Physiological; Prevention; Publications; Rattus; Regulation; Relapse; Reporting; Research; Role; Salvia; Self Administration; Stress; Structure; System; alcohol effect; analog; chronic pain; delta opioid receptor; design; enantiomer; endogenous opioids; immune function; kappa opioid receptors; naltrexol; neoclerodane; novel; phenylmorphan; prevent; receptor; reinforced behavior; tool

Significant progress was made in the last reporting period, resulting in five publications. We reported on the synthesis and opioid binding affinity of the final pair of oxide-bridged phenylmorphans, the ortho- and para-b-isomers and their N-phenethyl analogues, and the synthesis of the N-phenethyl analogues of the ortho- and para-d-isomers. Another study described the synthesis and pharmacological effects of the enantiomers of the N-phenethyl analogues of the ortho and para e- and f-oxide-bridged phenylmorphans. We also reported the design, synthesis, and characterization of 6beta-naltrexol analogs, and their selectivity for in vitro opioid receptor subtypes and provided new information on the role of the furan in affinity of neoclerodane diterpenes from Salvia divinorum for opioid receptors.

上一个报告期取得了重大进展，出版了五份出版物。我们报道了最后一对氧化物桥联苯吗啡烷、邻位和对位b-异构体及其N-苯乙基类似物的合成和阿片类药物结合亲和力，以及邻位和对位N-苯乙基类似物的合成-d-异构体。另一项研究描述了邻位和对位 e-和 f-氧化物桥接的苯基吗啡烷的 N-苯乙基类似物的对映体的合成和药理作用。 我们还报道了 6β-纳曲醇类似物的设计、合成和表征，及其对体外阿片受体亚型的选择性，并提供了有关呋喃在鼠尾草新氯丹二萜与阿片受体亲和力中的作用的新信息。