SYNTHESIS OF DELTA-9THC RELATED COMPOUNDS

Delta-9THC相关化合物的合成

• 批准号: 3211873
• 负责人: RAJ RAZDAN
• 金额: $ 23.05万
• 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 1992-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3211873
• 关键词: Rodentias; amides; cannabinoids; chemical group; chemoreceptors; drug abuse; drug abuse chemotherapy; drug addiction antagonist; drug design /synthesis /production; drug metabolism; isomer; mechlorethamine; psychotropic drugs

The drug abuse problem in general and the wide spread use of marijuana in particular has focused attention on the chemistry and pharmacology of this plant (Cannabis Sativa). 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 our synthetic program is to develop delta 9- tetrahydrocannabinol (THC) analogs which will prove to be useful tools in elucidating the mechanism of action of cannabinoids. Our specific aims are to synthesize (i) a series of delta 9,11-THCs with varied aromatic side-chains as potential antagonists based on a lead that in the monkey test, pretreatment with delta 9,11-THC attenuated the delta 9-THC induced ptosis, sedation, ataxia and operant behavior; (ii) delta 8-THC analogs with the N-bis(2- chloroethyl) functional group present at C-11, 12 beta-, 3'- and 5'-positions as potential receptor probes and antagonists; (iii) three pairs of C-2', 3'- and 4'-hydroxy- delta 9-THC in their R and S forms; and (iv) a series of amide derivatives of 9-nor-9-carboxy- delta 8-THC as potential antagonists. The synthesis of these analogs and their subsequent biological evaluation could provide us with new knowledge about Structure Activity Relationships (SAR) in cannabinoids; it could lead to the discovery of an antagonist which would help in the identification of cannabinoid receptors and thus result in a rapid advance in this field. The discovery of an antagonist will also prove to be a valuable tool in assessing the dependence producing properties of delta 9-THC. The proposed study will give a deeper understanding, at least in part, of the mechanisms involved in the pharmacological action of these compounds and will help to combat the drug abuse problem which has had profound effects on our present day society.

总体上，药物滥用问题以及广泛使用 尤其是大麻的重点是化学和 该植物的药理学（大麻萨蒂瓦）。 虽然很快 在化学和药理学方面取得了进步 化合物类别，产生的机制 尚未建立各种中枢神经效应（CNS）。 我们合成计划的长期目标是开发Delta 9- 四氢大麻酚（THC）类似物被证明是有用的 阐明大麻素作用机理的工具。 我们的具体目的是综合（i）一系列Delta 9,11-THC 基于 在猴子测试中的领先优势，使用Delta 9,11-THC进行预处理 减弱了9-THC诱导的ptosis，镇静，共济失调和 操作行为； （ii）n-bis的delta 8-thc类似物（2- 氯乙基）功能组存在于C-11、12β-，3'-和 5'位置作为潜在的受体探针和拮抗剂； （iii） 三对C-2'，3'-和4'Hydroxy-delta 9-thc在他们的R和 S形式； （iv）9-NOR-9-羧基的一系列酰胺衍生物 - Delta 8-THC作为潜在的拮抗剂。 这些的综合 类似物及其随后的生物学评估可以提供 我们有关于结构活动关系的新知识（SAR） 在大麻素中；它可能导致发现对手 这将有助于鉴定大麻素受体和 因此，该领域的进步迅速。 发现 对手也将被证明是评估评估的有价值工具 依赖性产生三角洲9-thc的特性。 拟议的研究 至少部分地将 涉及这些药理作用的机制 化合物，将有助于解决有药物滥用问题 对我们当今的社会产生了深远的影响。