一种烟碱乙酰胆碱受体(nAChRs)显像前体化合物的合成与125I标记研究

本文介绍一种可用于125/123I标记的A-85380类前体化合物--(S)-5-(三丁基锡烷基)-3-1-(叔丁氧基羰基)-2-甲氧基]氮杂环丁基]吡啶的设计、合成及125I标记研究.实验以2-糠胺和(S)-氮杂环丁基甲酸为起始物,先合成(S)-5-(三丁基锡烷基)-3-1-(叔丁氧基羰基)-2-氮杂环丁基]甲氧基]吡啶前体化合物,再用125I标记,制得5-125I]I-A-85380.整个放射性标记的时间为50-55min,标记率大于30%.5-125I]I-A-85380在室温下放置3天,其放化纯度仍在95%以上,表明其在体外具有较高的稳定性.

Synthesis and 125I labeling of a precursor for imaging nicotinic acetylcholine receptors

Nicotinic Acetylcholine Receptors (nAChRs) are involved in various pharmacological effects or diseases, such as Alzheimer's Disease, Parkinson's Disease and tobacco addiction. It will be very appealing to image nAChRs in vivo, diagnose and treat the above diseases, and probe the mechanism of nAChRs in tobacco addiction if the suitable radioactive labeled compound can be synthesized. In this study, (s)-5-(tri-butylstannyl)-3{1-(tert-butoxycarbonyl)-2- azetidinyl]methoxy}pyridine, a precursor for imaging nAChRs, was synthesized with commercial 2-furfurylamine and (s)-2-azetidinecarboxylic acid as starting materials, and was further labeled with 125/123I.The whole procedure for radiosynthesis needs 50 - 55 min and more than 30% of the 125I are found in the purified 5-125I]-A-85380. Even staying for 3 days at room temperature in vitro, the purified 5-125I]-I-85380 can maintain its stability, with a radiochemical purity of more than 95%.