ANALOGS OF METHYLLYCACONITINE--SELECTIVE NICOTINIC AGENT
甲基乌头碱类似物--选择性烟碱剂
基本信息
- 批准号:2898591
- 负责人:
- 金额:$ 4.66万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-08-01 至 2000-05-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION: (Applicant's Abstract)
We have discovered a simple analog of methyllycaconitine (MLA) that acts as a
micromolar inhibitor at the nicotinic acetylcholine receptor nAChR). This
should be a fertile area from which to find selective and potent antagonists of
subtypes of the nAChR. The goal of this proposal is to quickly outline an SAR
(Structure Activity Relationship) of this new lead compound in order to assess
structural requirements necessary for potency and selectivity. This will lead
to new pharmacological tools as well as aid in the development of novel nAChR
antagonists as drugs.
Through a systematic evaluation of substituents on the nitrogen of the
piperidine ring as well as alterations to the piperidine ring itself, we will
determine an optimal group with regard to potency and receptor subtype
specificity. We will also prepare differently substituted imides in order to
determine the optimal placement with regard to potency and receptor subtype
specificity. All analogs will be evaluated with regard to the potency and
receptor subtype specificity.
MLA is extremely interesting as a lead compound for the development of new
nAChR antagonists. MLA is the most potent non-peptide nAChR antagonist
currently known. Since the availability of MLA from natural sources is limited,
very little work on understanding the SAR of MLA has been reported. While
several analogs of MLA have been synthesized only a few reports of biological
activity have been published. These previous analogs have failed to fully
define the pharmacophore of MLA.
We describe a series of analogs that will allow us to develop a detailed
pharmacophore of the nicotinic antagonist MLA. Our analogs are novel, rapidly
prepared, and target the two most significant portions of MLA for study. These
key structural features will allow us to expeditiously arrive at a detailed
pharmacophore for MLA. These studies have the potential to be the first step
for extensive future work on the design and discovery of novel nicotinic
agents. These types of compounds have potential use as pharmacological tools
and aids in understanding and treating nicotine addiction.
描述:(申请人摘要)
我们已经发现了一种简单的类似物甲基乌头碱(MLA),
烟碱乙酰胆碱受体nAChR的微摩尔抑制剂)。这
应该是一个肥沃的领域,从中找到选择性和有效的拮抗剂,
nAChR的亚型。该提案的目标是快速勾勒出一个特区
(结构活性关系),以评估
效力和选择性所必需的结构要求。这将导致
新的药理学工具,以及在新的nAChR的发展援助
拮抗剂作为药物。
通过系统地评价化合物的氮上的取代基,
哌啶环以及哌啶环本身的改变,我们将
根据效力和受体亚型确定最佳组
的特异性我们还将制备不同取代的酰亚胺,
根据效价和受体亚型确定最佳放置位置
的特异性将评价所有类似物的效力,
受体亚型特异性
MLA作为开发新药物的先导化合物非常有趣
nAChR拮抗剂。MLA是最有效的非肽类nAChR拮抗剂
目前已知。由于从自然来源获得的司法协助有限,
据报告,在了解司法协助的SAR方面开展的工作很少。而
已经合成了MLA的几种类似物,
活动已经公布。这些以前的类似物未能完全
确定MLA的药效团。
我们描述了一系列类似物,这将使我们能够开发一个详细的
烟碱拮抗剂MLA的药效团。我们的类似物是新颖的,
准备,并针对MLA的两个最重要的部分进行研究。这些
关键的结构特征将使我们能够迅速达成详细的
MLA的药效团。这些研究有可能成为
用于设计和发现新型尼古丁的广泛未来工作
剂.这些类型的化合物具有作为药理学工具的潜在用途
并有助于理解和治疗尼古丁成瘾。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Stephen C. Bergmeier其他文献
Cholinergic Agents: Effect of Methyl Substitution in a Series of Arecoline Derivatives on Binding to Muscarinic Acetylcholine Receptors
- DOI:
10.1002/jps.2600811012 - 发表时间:
1992-10-01 - 期刊:
- 影响因子:
- 作者:
Walter H. Moos;Stephen C. Bergmeier;Linda L. Coughenour;Robert E. Davis;Fred M. Hershenson;Jeffrey A. Kester;James S. McKee;John G. Marriott;Roy D. Schwarz;Haile Tecle;Anthony J. Thomas - 通讯作者:
Anthony J. Thomas
A SYNTHESIS OF HEXAHYDRO-H-OXAZOLO[3,4-a]PYRAZIN-3-ONES FROM FUSED AZIRIDINES
稠合氮丙啶合成六氢-H-恶唑并[3,4-a]吡嗪-3-酮
- DOI:
- 发表时间:
2016 - 期刊:
- 影响因子:0
- 作者:
Stephen C. Bergmeier;F. Fang;I. Maciągiewicz - 通讯作者:
I. Maciągiewicz
Substitution effects in intramolecular aziridine–allylsilane cyclizations
- DOI:
10.1016/j.tet.2008.11.043 - 发表时间:
2009-01-24 - 期刊:
- 影响因子:
- 作者:
David J. Lapinsky;Aravinda B. Pulipaka;Stephen C. Bergmeier - 通讯作者:
Stephen C. Bergmeier
Stephen C. Bergmeier的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Stephen C. Bergmeier', 18)}}的其他基金
ANALOGS OF METHYLLYCACONITINE--SELECTIVE NICOTINIC AGENT
甲基乌头碱类似物--选择性烟碱剂
- 批准号:
6294089 - 财政年份:1999
- 资助金额:
$ 4.66万 - 项目类别:
ANALOGS OF METHYLLYCACONITINE--SELECTIVE NICOTINIC AGENT
甲基乌头碱类似物--选择性烟碱剂
- 批准号:
6175492 - 财政年份:1999
- 资助金额:
$ 4.66万 - 项目类别:
相似海外基金
Development and Translation Mass Spectrometry Methods to Determine BioMarkers for Parkinson's Disease and Comorbidities
确定帕金森病和合并症生物标志物的质谱方法的开发和转化
- 批准号:
2907463 - 财政年份:2024
- 资助金额:
$ 4.66万 - 项目类别:
Studentship
Development of a predictive biomarker for Parkinson's disease
帕金森病预测生物标志物的开发
- 批准号:
MR/Y019415/1 - 财政年份:2024
- 资助金额:
$ 4.66万 - 项目类别:
Research Grant
Promoting Parkinson's disease trial participation in rural and coastal communities
促进农村和沿海社区参与帕金森病试验
- 批准号:
2898794 - 财政年份:2024
- 资助金额:
$ 4.66万 - 项目类别:
Studentship
Neurophysiological mechanism underlying freezing of gait in Parkinson's disease: transcutaneous spinal cord stimulation for gait disturbance
帕金森病步态冻结的神经生理机制:经皮脊髓刺激治疗步态障碍
- 批准号:
23K10409 - 财政年份:2023
- 资助金额:
$ 4.66万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Inhibition of cell-to-cell propagation of alpha-synuclein aggregation by glial cells and its involvement in neuropathology in Parkinson's disease.
神经胶质细胞抑制α-突触核蛋白聚集的细胞间传播及其参与帕金森病的神经病理学。
- 批准号:
23K06928 - 财政年份:2023
- 资助金额:
$ 4.66万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Propagation of a-synuclein in Parkinson's disease progress
α-突触核蛋白在帕金森病进展中的传播
- 批准号:
22KJ2095 - 财政年份:2023
- 资助金额:
$ 4.66万 - 项目类别:
Grant-in-Aid for JSPS Fellows
The Diagnostic and Prognostic Utility of Eye Tracking in Parkinson's Disease and Related Disorders
眼动追踪在帕金森病及相关疾病中的诊断和预后效用
- 批准号:
479285 - 财政年份:2023
- 资助金额:
$ 4.66万 - 项目类别:
Operating Grants
Drug-microbiome-host interactions in Parkinson's disease
帕金森病的药物-微生物组-宿主相互作用
- 批准号:
2881438 - 财政年份:2023
- 资助金额:
$ 4.66万 - 项目类别:
Studentship
MICA: How does the pedunculopone nucleus influence treatment responses in Parkinson's disease, and can it be targeted for new treatment strategies
MICA:脚核如何影响帕金森病的治疗反应,是否可以作为新治疗策略的目标
- 批准号:
MR/X005267/1 - 财政年份:2023
- 资助金额:
$ 4.66万 - 项目类别:
Research Grant
Ordering the disordered in Parkinson's disease to derive peptide inhibitors of alpha-synuclein toxicity
命令帕金森病患者衍生出α-突触核蛋白毒性的肽抑制剂
- 批准号:
2884235 - 财政年份:2023
- 资助金额:
$ 4.66万 - 项目类别:
Studentship