Delta9-Tetrahydrocannabinol Related Compounds

描述（由申请人提供）：一般的药物滥用问题，特别是大麻的广泛使用，已经将注意力集中在大麻素的化学和药理学上。尽管这类化合物的化学和药理学取得了快速进展，但产生各种中枢神经效应（CNS）的机制尚未确定。合成计划的长期目标是开发δ-9-四氢大麻酚（THC）类似物，其将被证明是阐明大麻素作用机制的有用工具。目前的重点是：（a）开发具有特定药理学特性的大麻素类似物作为镇痛剂（B）检查“沉默拮抗剂”的特性（c）开发和设计CB 2选择性配体（d）研究THC中C-I取代基在“配体-受体”相互作用中的作用和（e）描绘大麻素的外周和中枢效应。所有这些目标代表了当前计划的继续，该计划已经产生了几个值得注意的线索。具体目标是（1）开发具有选择性药理学特征的激动剂，（2）开发“沉默拮抗剂”，（3）开发CB 2选择性THC，（4）检查C-I取代基与受体相互作用的性质，（5）研究外周作用激动剂和拮抗剂;（6）产生新的生物先导物。从这些类似物的合成和药理学研究中获得的知识对于研究构效关系（SAR）、耐受性、依赖性和开发治疗有用的药物至关重要。并将导致更好地了解大麻素的作用机制，并将有助于打击药物滥用问题。

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 delta-9-tetrahvdrocannabinol (THC) analogs which will prove to be useful tools in elucidating the mechanism of action of cannabinoids. The present emphasis will be directed toward: (a) developing cannabinoid analogs with a specific pharmacological profile as analgesics (b) examining the profile of the 'silent antagonist' (c) developing and designing CB2 selective ligands (d) studying the role of the C-I substituent in THCs in 'ligand-receptor' interactions and (e) delineating between peripheral and central effects of cannabinoids. All these goals represent a continuation of the current program which has generated several noteworthy leads.The specific aims are (1) development of agonists with selective pharmacological profiles, (2) development of 'silent antagonists', (3) development of CB2 selective THCs, (4) examine the nature of C-I substituent interactions with the receptor, (5) study peripheral acting agonists and antagonists 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.