Synthesis and biological evaluation of 3-alkyl-dihydrotetrabenazine derivatives as vesicular monoamine transporter-2 (VMAT2) ligands.
Synthesis and biological evaluation of 3-alkyl-dihydrotetrabenazine derivatives as vesicular monoamine transporter-2 (VMAT2) ligands.
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DOI：
10.1016/j.bmcl.2011.03.113
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发表时间：
2011-06
影响因子：
2.7
通讯作者：
Pinguan Zheng;B. Lieberman;S. Choi;Karl Plöessl;H. Kung
中科院分区：
文献类型：
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作者：
Pinguan Zheng;B. Lieberman;S. Choi;Karl Plöessl;H. Kung
在寻找新的囊泡单胺转运蛋白2 （VMAT2）的体内脑成像探针的过程中，我们开发了一系列新的3-烷基二氢四苯那嗪（DTBZ）衍生物的高效合成方法。用[125I]-碘乙烯基- tbz或[18F](+)-FP-DTBZ作为放射配体，在大鼠纹状体组织匀浆中进行体外抑制结合试验，评估VMAT2的亲和力。新的DTBZ衍生物对VMAT2具有中等到良好的结合亲和力。在这些新配体中，化合物4b对VMAT2的亲和力最好（Ki= 5.98 nM），可能是未来结构活性研究的有用先导化合物。
In the search of new probes for in vivo brain imaging of vesicular monoamine transporter type 2 (VMAT2), we have developed an efficient synthesis of a novel series of 3-alkyl-dihydrotetrabenazine (DTBZ) derivatives. The affinity of VMAT2 was evaluated by an in vitro inhibitory binding assay using [125I]-iodovinyl-TBZ or [18F](+)-FP-DTBZ as radioligands in rat striatal tissue homogenates. New DTBZ derivatives exhibited moderate to good binding affinity to VMAT2. Among these new ligands, compound4bshowed the best affinity for VMAT2 (Ki= 5.98 nM) and may be a useful lead compound for future structure–activity studies.