Piperidine Derivatives as Radiotracers for Serotonin Transporters
Piperidine Derivatives as Radiotracers for Serotonin Transporters
批准号:
6681288
负责人:
GILLES D TAMAGNAN
金额:
$11.74万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2003
资助国家:
美国
项目状态:
已结题
起止时间:
2003-08-14 至 2005-07-31
中文摘要
描述(由申请人提供):
本研究项目的目标是定义配体的结构和放射性标记,从而允许通过正电子(PET)或单光子(SPECT)发射断层扫描的外部成像定量测量活体脑中的5-羟色胺转运体(5-HTT)位点。5-羟色胺转运蛋白在多种生理和病理生理过程中发挥作用,特别是在抑郁症、焦虑症、季节性情感障碍、贪食症和精神病中,如尸检和初步成像研究所示。特异性结合5-HTT的放射性示踪剂将在此类疾病的诊断、监测治疗和研究中具有很大的实用性。然而,还没有合适的示踪剂,允许定量的大脑区域与低密度的5-HTT,如皮质。基于使用经典结构-活性关系方法的初步体外结合结果,我们发现苯基托烷的某些4 '-联苯类似物显示出对5-HTT的纳摩尔亲和力和相对于其他单胺转运蛋白的>50倍选择性。在本申请中,我们提出测试以下假设:1)在4-苯基哌啶的4 ′-位上具有π-供体取代基的衍生物相对于多巴胺转运体(DAT)和去甲肾上腺素转运体(NET)将有利于与5-HTT结合;和2)消除托烷的C6-C7桥(以产生哌啶类似物)将降低我们的化合物的亲脂性,并且具有比相应的托烷或去甲托烷化合物更低的非特异性结合。
英文摘要
DESCRIPTION (provided by applicant):
The goal of this research project is to define the structure and radioactive label for ligands that will permit quantitative measurement of serotonin transporter (5-HTT) sites in living brain by external imaging with positron (PET) or single photon (SPECT) emission tomography. The serotonin transporter is known to play a role in several physiological and pathophysiological processes, especially in depression, anxiety, seasonal affective disorder, bulimia, and psychosis, as demonstrated by post-mortem and preliminary imaging studies. A radiotracer that bound specifically to 5-HTT would be of great utility in diagnosis, monitoring treatment, and research of such disorders. However, there is not yet a suitable tracer that allows quantitation in areas of the brain with low densities of 5-HTT, such as the cortex. Based on preliminary in vitro binding results using a classical structure-activity relationship approach, we found that certain 4'-biphenyl analogs of phenyltropanes showed nanomolar affinity to 5-HTT and >50-fold selectivity with respect to other monoamine transporters. In this application we propose to test the following hypotheses: 1) derivatives with pi-donor substituents on the 4'-position of 4-phenyl piperidine will favor binding to 5-HTT relative to dopamine transporter (DAT) and norepinephrine transporter (NET); and 2) elimination of the C6-C7 bridge of the tropane (to yield piperidine analogs) will reduce the lipophilicity of our compounds and have lower nonspecific binding than the corresponding tropane or nor-tropane compound.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
A Program for Innovative PET Radioligand Development and Application - a translational toolbox for treatments for Mental Health
-
批准号:8957207
-
项目类别:
-
资助金额:$107.67万
-
财政年份:2015
-
负责人:GILLES D TAMAGNAN
-
依托单位:
In vivo evaluation of a new ligand with picomolar affinity for the serotonin tran
-
批准号:7547066
-
项目类别:
-
资助金额:$25.0万
-
财政年份:2008
-
负责人:GILLES D TAMAGNAN
-
依托单位:
In vivo evaluation of a new ligand with picomolar affinity for the serotonin tran
-
批准号:7399724
-
项目类别:
-
资助金额:$25.0万
-
财政年份:2008
-
负责人:GILLES D TAMAGNAN
-
依托单位:
Detection of Amyloid Plaques
-
批准号:7456522
-
项目类别:
-
资助金额:$24.15万
-
财政年份:2007
-
负责人:GILLES D TAMAGNAN
-
依托单位:
Detection of Amyloid Plaques
-
批准号:7266612
-
项目类别:
-
资助金额:$25.84万
-
财政年份:2007
-
负责人:GILLES D TAMAGNAN
-
依托单位:
Indole Glyoxylamides Peripheral Benzodiazepine Receptor
-
批准号:7110892
-
项目类别:
-
资助金额:$24.92万
-
财政年份:2006
-
负责人:GILLES D TAMAGNAN
-
依托单位:
Indole Glyoxylamides Peripheral Benzodiazepine Receptor Radiotracers
-
批准号:7244240
-
项目类别:
-
资助金额:$25.08万
-
财政年份:2006
-
负责人:GILLES D TAMAGNAN
-
依托单位:
AZABICYCLONONANE SEROTONIN TRANSPORTER RADIOTRACERS
-
批准号:6950024
-
项目类别:
-
资助金额:$25.0万
-
财政年份:2004
-
负责人:GILLES D TAMAGNAN
-
依托单位:
AZA BICYCLO NONANE SEROTONIN TRANSPORTER RADIOTRACERS
-
批准号:6790750
-
项目类别:
-
资助金额:$25.0万
-
财政年份:2004
-
负责人:GILLES D TAMAGNAN
-
依托单位:
Novel VMAT 2 Radioligand for Imaging Parkinson's
-
批准号:6691941
-
项目类别:
-
资助金额:$25.0万
-
财政年份:2003
-
负责人:GILLES D TAMAGNAN
-
依托单位:
Piperidine Derivatives as Radiotracers for Serotonin Transporters
-
批准号:6791368
-
项目类别:
-
资助金额:$11.39万
-
财政年份:2003
-
负责人:GILLES D TAMAGNAN
-
依托单位:
A Novel VMAT 2 Radioligand for Imaging Parkinson's
-
批准号:6802275
-
项目类别:
-
资助金额:$25.0万
-
财政年份:2003
-
负责人:GILLES D TAMAGNAN
-
依托单位:
DEVELOPMENT OF PET AND SPECT LIGANDS FOR mGluR5 IMAGING
-
批准号:6665219
-
项目类别:
-
资助金额:$19.09万
-
财政年份:2002
-
负责人:GILLES D TAMAGNAN
-
依托单位:
DEVELOPMENT OF PET AND SPECT LIGANDS FOR mGluR5 IMAGING
-
批准号:7122885
-
项目类别:
-
资助金额:$26.85万
-
财政年份:2002
-
负责人:GILLES D TAMAGNAN
-
依托单位:
DEVELOPMENT OF PET AND SPECT LIGANDS FOR mGluR5 IMAGING
-
批准号:6805929
-
项目类别:
-
资助金额:$33.98万
-
财政年份:2002
-
负责人:GILLES D TAMAGNAN
-
依托单位:
DEVELOPMENT OF PET AND SPECT LIGANDS FOR mGluR5 IMAGING
-
批准号:6746985
-
项目类别:
-
资助金额:$4.86万
-
财政年份:2002
-
负责人:GILLES D TAMAGNAN
-
依托单位:
DEVELOPMENT OF PET AND SPECT LIGANDS FOR mGluR5 IMAGING
-
批准号:6944339
-
项目类别:
-
资助金额:$2.12万
-
财政年份:2002
-
负责人:GILLES D TAMAGNAN
-
依托单位:
DEVELOPMENT OF PET AND SPECT LIGANDS FOR mGluR5 IMAGING
-
批准号:6552663
-
项目类别:
-
资助金额:$14.59万
-
财政年份:2002
-
负责人:GILLES D TAMAGNAN
-
依托单位:
DEVELOPMENT OF PET AND SPECT LIGANDS FOR mGluR5 IMAGING
-
批准号:7235207
-
项目类别:
-
资助金额:$61.61万
-
财政年份:2002
-
负责人:GILLES D TAMAGNAN
-
依托单位:
海外基金