ANANDAMIDE--STRUCTURE/ACTIVITY RELATIONSHIPS

阿南达酰胺--结构/活性关系

• 批准号: 2468014
• 负责人: RAJ RAZDAN
• 金额: $ 12.09万
• 依托单位: ORGANIX, INC.
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-02-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2468014
• 关键词: amidases; analog; anandamide; arachidonate; cannabinoids; chemical structure function; chemical synthesis; enzyme inhibitors; ethanolamines

DESCRIPTION (Applicant's Abstract): The drug abuse problem in general and the widespread use of marijuana in particular have focused attention on the chemistry and pharmacology of the plant Cannabis saliva. Although rapid advances have been made in the chemistry and pharmacology of this class of compound called cannabinoids, the mechanisms involved in producing the various central nervous effects have not been established. A few years ago, it was shown that cannabinoids act by binding to a G-protein-coupled receptor in the brain (CB1), and arachidonylethanolamide called anandamide (AN), was identified as the endogenous ligand. The long term goal of this program is to develop the Structure-Activity Relationships (SAR) of ANs which are eicosanoids, and bear no chemical/structural relationship with cannabinoids. We feel the SAR of ANs will be critical for understanding how AN and cannabinoids interact with the same receptor. The present emphasis will be directed toward developing (1) potent agonists and potential antagonists; (2) novel structural analogs; (3) hydroxy-AN analogs as potential metabolites and (4) selective amidase inhibitors. All these goals represent a continuation of the current program which has generated several noteworthy leads. The specific aims are to (1) continue to examine the SAR of arachidonic acid part of AN; (2) continue to examine the SAR of the ethanolamine part of AN; (3) synthesize hydroxylated AN analogs; (4) develop novel AN/THC analogs; (5) develop a selective and potent amidase inhibitor. The synthesis of these analogs and their subsequent biological evaluation will provide us with SAR in the AN series and will highlight the differences which may exist between this series and THCs and allow a better understanding of their interrelationship. The data could point us in the direction of cannabinoid receptor sub-types and even help in the discovery of an antagonist. In addition they will provide cannabinoid probes for both in vitro and in vivo studies. The proposed study will therefore help in our understanding of the pharmacological action of this important class of compounds.

描述（申请人的摘要）： 总体上，药物滥用问题以及大麻在 特别是将注意力集中在化学和药理学上 植物大麻唾液。 尽管在 这类化合物的化学和药理学称为大麻素， 产生各种中枢神经效应的机制 尚未建立。 几年前，显示大麻素 通过与大脑中的G蛋白偶联受体结合起作用（CB1）和 称为anandamide（AN）的蛛网乙醇胺被确定为 内源配体。 该计划的长期目标是开发 eicosanoids ANS的结构活性关系（SAR）和 与大麻素无化学/结构关系。 我们感觉到SAR ANS的重要性对于理解一个和大麻素如何相互作用至关重要 带有相同的受体。 目前的重点将指向 发展（1）有效的激动剂和潜在的拮抗剂； （2）小说 结构类似物； （3）羟基-AN类似物作为潜在代谢产物和（4） 选择性amidase抑制剂。 所有这些目标代表了延续 当前的程序产生了几个值得注意的潜在客户。 具体目的是（1）继续检查蛛网酸的SAR a的一部分； （2）继续检查A的乙醇胺部分的SAR； （3）合成羟基化的类似物； （4）发展新颖的AN/THC类似物； （5）开发一种选择性和有效的amidase抑制剂。 这些类似物的合成及其随后的生物学评估 将为我们提供一个系列中的SAR，并将突出差异 这可能存在于本系列和THC之间，并允许更好 了解他们的相互关系。 数据可以将我们指向 大麻素受体子类型的方向，甚至有助于发现 对手。 另外，它们将为两者提供大麻素探针 体外和体内研究。 因此，拟议的研究将有助于我们 了解这一重要类的药理作用 化合物。