Synthesis of ring- and side-chain-substituted m-iodobenzylguanidine analogues
Synthesis of ring- and side-chain-substituted m-iodobenzylguanidine analogues
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DOI：
10.1021/bc010031z
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发表时间：
2001-09-01
影响因子：
4.7
通讯作者：
Zalutsky, MR
中科院分区：
文献类型：
--
作者：
Vaidyanathan, G;Shankar, S;Zalutsky, MR
为了开发具有改进的靶向性质的MIBG类似物，特别是用于肿瘤学应用的MIBG类似物，合成了几种放射性碘化的环和侧链取代的MIBG类似物。除了3-[I-131]碘-4-硝基苄基胍和N-羟基-3-[I-131]碘苄基胍外，放射性碘化类似物均以不加载体的水平从其各自的锡前体制备。放射化学产率通常在70-90%范围内，除了3-氨基-5- [I-131]碘苄基胍，其放射化学产率约为40%。虽然硅前体N-1，N-2-双（叔丁氧基羰基）-N-1-（4-硝基-3-三甲基甲硅烷基苄基）胍没有产生3-[I-131]碘-4-硝基苄基胍，但其脱保护的衍生物N-1-（4-硝基-3-三甲基甲硅烷基苄基）胍以20%的适度产率被放射性碘化，得到3-[I-131]碘-4-硝基苄基胍。3-碘-4-硝基苄胍经交换放射碘化得到3-[I-131]碘-4-硝基苄胍，放化产率80%。[I-131]NHIBG是由其硅前体N-1-羟基-N-3-（3-三甲基硅基苄基）胍以85%的放化产率合成的。
With the goal of developing MIBG analogues with improved targeting properties especially for oncologic applications, several radioiodinated ring- and side-chain-substituted MIBG analogues were synthesized. Except for 3-[I-131]iodo-4-nitrobenzylguanidine and N-hydroxy-3-[I-131]iodobenzylguanidine, the radio-iodinated analogues were prepared at no-carrier-added levels from their respective tin precursors. The radiochemical yields generally were in the range of 70-90% except for 3-amino-5- [I-131]iodobenzylguanidine for which a radiochemical yield of about 40% was obtained. While the silicon precursor N-1,N-2-bis(tert-butyloxycarbonyl)-N-1-(4-nitro-3-trimethylsilylbenzyl)guanidine did not yield 3-[I-131]iodo-4-nitrobenzylguanidine, its deprotected derivative, N-1-(4-nitro-3-trimethylsilylbenzyl)guanidine was radioiodinated in a modest yield of 20% providing 3-[I-131]iodo-4-nitrobenzylguanidine. Exchange radioiodination of 3-iodo-4-nitrobenzylguanidine gave 3-[I-131]iodo-4-nitrobenzylguanidine in 80% radiochemical yield. No-carrier-added [I-131]NHIBG was prepared from its silicon precursor N-1-hydroxy-N-3-(3-trimethylsilylbenzyl)guanidine in 85% radiochemical yield.