SYNTHESIS OF DELTA-9THC RELATED COMPOUNDS

普遍的药物滥用问题和毒品的广泛使用 尤其是大麻，人们把注意力集中在化学和 这种植物的药理作用(大麻属)。虽然速度很快 在化学和药理学方面取得了进展。 一类化合物，所涉及的产生 各种中枢神经效应(CNS)尚未确定。 我们综合计划的长期目标是开发三角洲9- 四氢大麻酚(THC)类似物将被证明是有用的 阐明大麻素作用机制的工具。 我们的具体目标是合成(I)一系列三角洲9，11-THC 以不同的芳香族侧链作为潜在的拮抗剂 在猴子试验中领先，用Delta 9，11-THC预处理 减轻Delta9-THC引起的上睑下垂、镇静、共济失调和 工作行为；(Ii)与N-双(2-)类似的增量8-THC 氯乙基)官能团存在于C-11、12β-、3‘-和 作为潜在受体探针和拮抗剂的5‘-位； 三对C-2‘，3’-和4‘-羟基-三角洲9-THC的R和 S形成；和(Iv)一系列9-去甲基-9-羧基-2，4-氨基-2-甲基-4-羟基-4-氨基-2，4-二甲氧基-2，4，4，4-二羟基-4-氨基-2，4，4，4，4-二羟基-4-氨基-4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4，4 Delta 8-THC作为潜在的拮抗剂。这些化合物的合成 类似物及其随后的生物学评价可以提供 美国对结构活性关系(SAR)的新认识 在大麻类药物中；它可能导致发现一种拮抗剂 这将有助于识别大麻素受体和 从而推动了这一领域的快速发展。发现了一种 对抗者也将被证明是评估 Delta9-THC的依赖产生性质。建议进行的研究 将使我们更深入地理解，至少在一定程度上， 这些化合物的药理作用机制 化合物，并将有助于打击药物滥用问题， 对我们今天的社会产生了深远的影响。

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.