ANANDAMIDE CONFORMERS TO PROBE THE CANNABINOID RECEPTOR

大麻素构象探索大麻素受体

基本信息

  • 批准号:
    2749124
  • 负责人:
  • 金额:
    $ 12.25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1996
  • 资助国家:
    美国
  • 起止时间:
    1996-09-01 至 2001-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION: (Applicant's Abstract) The systematic study of analogs of the endogenous cannabimimetic, anandamide, has the long term, health related potential to further knowledge of the biochemical mechanism of action of this neurotransmitter and the new neurochemical system it represents. Mapping of ligand interaction sites and the identification of receptor subtypes are additional objectives. Also, analogs could be generated with dissociated pharmacological effects resulting in more specific drugs and biochemical probes with psycho dynamic activities of interest. These have potential application to studies of drug abuse, brain function, and immuno-modulation. The specific aims of the proposed work is the design, synthesis, pharmacological testing, and molecular modeling of conformationally restricted anandamide analogs to probe a sector of conformational space that chemical and computational data suggest as the active conformation of anandamide. It is theorized that the active conformation of anandamides is a bent or "J" like structure which exhibits remarkable overlap with active cannabinoids as regards both shape and electrostatic potentials at its receptor accessible surface. Locking such conformations is expected to enhance activities and potentially dissociate biological effects in this class of compounds. Compounds designed to test the theory are ring constrained structures, based on preliminary molecular dynamics studies of anandamide and reported chemistry of other arachidonic acid derivatives, that examines the hypothesized sector of conformational space with small, medium and macrocyclic ring analogs. The compounds explore the effects of the position of the bend in the acyclic 20-carbon chain of anandamide, the configurational differences at chiral centers, and the degree of conformational freedom as influenced by various ring systems. It is further theorized that interaction between the pi electrons of the ligand and cationic sites in the receptor play a key role in binding. This is tested in analogs with both enhanced and reduced pi character in a way that separates the conformational and the electrostatic effects of the carbon-carbon double bonds. Putative metabolites of anandamide and the analogs are examined as they are potential active forms of this class of ligands. The research program is designed to test and evolve an SAR theory and discover active analogs by computationally guided synthesis, in vitro and in vivo testing, and computational analysis to refine subsequent cycles of design, synthesis and testing. Testing will involve accepted receptor binding assays, inhibition of mouse isolated vas deferens twitch response, and in vivo testing in the mouse to identify active compounds.
描述:(申请人摘要)

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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HERBERT H SELTZMAN其他文献

HERBERT H SELTZMAN的其他文献

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{{ truncateString('HERBERT H SELTZMAN', 18)}}的其他基金

THERAPY FOR ALCOHOL USE DISORDER
酒精使用障碍的治疗
  • 批准号:
    10820349
  • 财政年份:
    2023
  • 资助金额:
    $ 12.25万
  • 项目类别:
Treatment for cannabis use disorder
大麻使用障碍的治疗
  • 批准号:
    10546566
  • 财政年份:
    2022
  • 资助金额:
    $ 12.25万
  • 项目类别:
Therapeutic Strategy for NASH
NASH 的治疗策略
  • 批准号:
    10323904
  • 财政年份:
    2021
  • 资助金额:
    $ 12.25万
  • 项目类别:
ANANDAMIDE CONFORMERS TO PROBE THE CANNABINOID RECEPTOR
大麻素构象探索大麻素受体
  • 批准号:
    2458453
  • 财政年份:
    1996
  • 资助金额:
    $ 12.25万
  • 项目类别:
ANANDAMIDE CONFORMERS TO PROBE THE CANNABINOID RECEPTOR
大麻素构象探索大麻素受体
  • 批准号:
    2123524
  • 财政年份:
    1996
  • 资助金额:
    $ 12.25万
  • 项目类别:
ANANDAMIDE CONFORMERS TO PROBE THE CANNABINOID RECEPTOR
大麻素构象探索大麻素受体
  • 批准号:
    2616076
  • 财政年份:
    1996
  • 资助金额:
    $ 12.25万
  • 项目类别:
MASTER AGREEMENT ORDER FOR CHEMICAL SYNTHESIS
化学合成主协议订单
  • 批准号:
    3608049
  • 财政年份:
    1992
  • 资助金额:
    $ 12.25万
  • 项目类别:
RESYNTHESIS OF COMPOUNDS FOR SCREENING
用于筛选的化合物的再合成
  • 批准号:
    3609379
  • 财政年份:
    1991
  • 资助金额:
    $ 12.25万
  • 项目类别:
MASTER AGREEMENT ORDER FOR CHEMICAL SYNTHESIS
化学合成主协议订单
  • 批准号:
    3608048
  • 财政年份:
    1991
  • 资助金额:
    $ 12.25万
  • 项目类别:
RESYNTHESIS OF COMPOUNDS FOR SCREENING
用于筛选的化合物的再合成
  • 批准号:
    3609381
  • 财政年份:
    1991
  • 资助金额:
    $ 12.25万
  • 项目类别:

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