新型神经降压素（8-13）模拟物的合成及生物学研究

Synthesis and biological studies of novel neurotensin(8-13) mimetics.

作者信息

Hong Feng, Zaidi Javid, Cusack Bernadette, Richelson Elliott

机构信息

Neuropsychopharmarcology Research, Mayo Clinic Jacksonville, 4500 San Pablo Road, FL 32224, USA.

出版信息

Bioorg Med Chem. 2002 Dec;10(12):3849-58. doi: 10.1016/s0968-0896(02)00342-5.

DOI:10.1016/s0968-0896(02)00342-5

PMID:12413837

Abstract

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.

摘要

新型神经降压素（NT）（8 - 13）（精氨酸（8）-精氨酸（9）-脯氨酸（10）-酪氨酸（11）-异亮氨酸（12）-亮氨酸（13））模拟物3、4是通过采用天然神经降压素（8 - 13）的所有内在官能团并使用取代吲哚作为模板来模拟NT（8 - 13）的药效团而设计的。对NT受体1亚型的生物学研究表明，3对大鼠和人神经降压素受体的结合亲和力分别为55和580 nM。作为比较，还合成了化合物5和6。3、4与5、6之间的结合差异表明了羧基在实现更高效NT（8 - 13）模拟物方面的重要性。