Synthesis of delta9-Tetrahydrocannabinol Related Compounds

δ9-四氢大麻酚相关化合物的合成

• 批准号: 7878709
• 负责人: Anuradha Mahadevan
• 金额: $ 34.81万
• 依托单位: ORGANIX, INC.
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-06-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7878709
• 关键词: AM356; Absence of pain sensation; Address; Affinity; Agonist; Allosteric Site; Anesthesia Adjuvants; Attention; Behavioral; Binding; Binding Sites; Biological; Brain; CNR1 gene; CNR2 gene; Cannabinoids; Carbon; Central Nervous System Agents; Chemical Structure; Chemicals; Chemistry; Cognition; Collaborations; Communities; Complex; Dependence; Depressed mood; Development; Dissociation; Drug Addiction; Drug abuse; Endocannabinoids; Experimental Designs; Generations; Goals; Hydrogen Bonding; Imidazole; Immunosuppression; Indoles; Inflammation; Knowledge; Lead; Learning; Ligands; Marijuana Smoking; Metabolic; Methods; Modification; Pain; Peripheral; Pharmaceutical Preparations; Pharmacology; Play; Positioning Attribute; Property; Pyrazoles; Research Personnel; Rewards; Role; SR 141716A; Salts; Series; Site; Structure-Activity Relationship; Sulfonamides; System; Tetrahydrocannabinol; Vasodilator Agents; Water; Work; abn-cbd; amino group; analog; anandamide; base; blood pressure regulation; cannabinoid receptor; combat; design; improved; in vivo; insight; interest; programs; quinoline analog; receptor; receptor binding; tool

DESCRIPTION (provided by applicant): The drug abuse problem in general and the wide spread use of marijuana in particular has focused attention on the chemistry and pharmacology of cannabinoids. Although rapid advances have been made in the chemistry and pharmacology of this class of compounds, the mechanisms involved in producing the various central nervous effects (CNS) have not been established. The long term goal of the synthetic program is to develop A9-tetrahydrocannabinol (THC) analogs which will prove to be useful tools in elucidating the mechanism of action of cannabinoids. The present emphasis will be directed towards: (a) development of CB1 selective agonists (b) development of allosteric modulators of the cannabinoid CB1 receptors (c) studying peripheral acting agonists and antagonists (d) elucidation of ligand-CB1 receptor iterations (e) development of CB1 neutral antagonist/inverse agonists which are structurally related to THC and (f) generation of new biological leads. All these goals represent a continuation of the current program which has generated several noteworthy leads. The specific aims are (1) development of CB1 selective agonists, (2) development of allosteric modulators of the CB1 receptors, (3) examining peripheral acting agonists and antagonists, (4) elucidation of ligand-CB1 receptor interactions, (5) development of CB1 neutral/inverse agonists which are structurally related to THC, and (6) generate new biological leads. The knowledge gained from the synthesis and pharmacological study of these analogs could be vital in the study of Structure Activity Relationships(SAR), tolerance, dependence and in the development of therapeutically useful drugs, and will lead to a better understanding of the mechanism of action of cannabinoids and will help combat the problem of drug abuse.

描述（由申请人提供）：通常，滥用药物问题，特别是大麻的广泛使用，将注意力集中在大麻素的化学和药理学上。尽管在这类化合物的化学和药理学方面已经取得了快速的进步，但尚未确定产生各种中枢神经效应（CNS）的机制。合成程序的长期目标是开发A9四氢大麻酚（THC）类似物，这些类似物将被证明是阐明大麻素作用机理的有用工具。 目前的重点将指向：（a）开发CB1选择性激动剂（b）开发大麻素CB1受体的变构调节因子（c）研究周围表演激动剂和拮抗剂（d）阐明cb1受体迭代（e）与中性抗体的结构型抗体抗体（E）与中性抗体的结构相关型抗体抗体（E）生物铅。所有这些目标代表了当前计划的延续，该计划产生了几个值得注意的线索。 具体目的是（1）CB1选择性激动剂的发展，（2）开发CB1受体的变构调节剂，（3）检查外围性作用激动剂和拮抗剂，（4）配体CB1受体相互作用阐明CB1中性/反相关的生物构造的cb1中性/反向型生物的生成（5）与结构性相关的构造（5）thc and thc and thc and thc and and tC和6C。 这些类似物的合成和药理学研究所获得的知识对于结构活性关系（SAR），耐受性，依赖性和治疗有用的药物的发展可能至关重要，并将更好地理解大麻素类动物的作用机制，并有助于解决药物滥用问题。