FKBP12-binding domain analogues of FK506 are potent, nonimmunosuppressive neurotrophic agents in vitro and promote recovery in a mouse model of Parkinson's disease

被引：40

作者：

Hamilton, GS

Huang, W

Connolly, MA

Ross, DT

Guo, H

Valentine, HL

Suzdak, PD

Steiner, JP

机构：

[1] Guilford Pharmaceuticals, Inc., Dept. of Research, Baltimore, MD 21224

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1997年 / 7卷 / 13期

关键词：

D O I：

10.1016/S0960-894X(97)00304-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of simple N-(glyoxyl)pipecolate esters were synthesized as mimics of the FKBP12-binding domain portion of FK506. Compounds which were effective inhibitors of the prolyl isomerase activity of FKBP12 were extraordinarily potent neurotrophic agents in vitro, and were effective in a mouse model of Parkinson's Disease. These results suggest that FKBP12 ligands have therapeutic utility in neurodegenerative diseases. (C) 1997 Elsevier Science Ltd.

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页码：1785 / 1790

页数：6

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