Synthesis and biological studies of novel neurotensin(8-13) mimetics
Synthesis and biological studies of novel neurotensin(8-13) mimetics
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DOI：
10.1016/s0968-0896(02)00342-5
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发表时间：
2002-12-01
影响因子：
3.5
通讯作者：
Richelson, E
中科院分区：
文献类型：
--
作者：
Feng, HJ;Zaidi, J;Richelson, E
采用天然神经降压素（8- 13）的全部功能基团，以取代吲哚为模板模拟NT（8 - 13）的药效团，设计了新的NT（8-13）（Arg（8）-Arg（9）-Pro（10）-Tyr（11）-Ile（12）-Leu（13））模拟物3，4。对NT受体亚型1的生物学研究表明，3对大鼠和人神经降压素受体分别具有55和580 nM的结合亲和力。还合成了化合物5和6。3、4和5、6之间的结合差异证明了羧基在获得更高效力的NT（8-13）模拟物中的重要性。(C)2002爱思唯尔科技有限公司版权所有。
Novel neurotensin (NT) (8-13) (Arg(8)-Arg(9)-Pro(10)-Tyr(11)-Ile(12)-Leu(13)) mimetics 3, 4 were designed by adopting all intrinsic functional groups of the native neurotensin(8-13) and using a substituted indole as a template to mimic the pharmacophore of NT(8-13). Biological studies at subtype 1 of the NT receptor showed that 3 has a 55 and 580 nM binding affinity at rat and human neurotensin receptors, respectively, As a comparison. compounds 5 and 6 were also synthesized. The binding difference between 3, 4 and 5, 6 argues the importance of the carboxylic group in achieving higher potency NT(8-13) mimetics. (C) 2002 Elsevier Science Ltd. All rights reserved.