Exploring the active site of phenylethanolamine N-methyltransferase with 3-hydroxyethyl- and 3-hydroxypropyl-7-substituted-1,2,3,4-tetrahydroisoquinolines

被引：7

作者：

Grunewald, GL

Romero, FA

Seim, MR

Criscione, KR

Deupree, JD

Spackman, CC

Bylund, DB

机构：

[1] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA

[2] Univ Nebraska, Med Ctr, Omaha, NE 68198 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 04期

关键词：

phenylethanolamine N-methyltransferase; enzyme inhibitors; tetrahydroisoquinoline; structure-based design;

D O I：

10.1016/j.bmcl.2004.12.013

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

3-Hydroxyethyl- and 3-hydroxypropyl-7-substituted-tetrahydroisoquinolines (9, 10, 16, and 17) were synthesized and evaluated for their phenylethanolamine N-methyltransferase (PNMT) inhibitory potency and affinity for the alpha(2)-adrenoceptor. Although alpha(2)-adrenoceptor affinity decreased for these compounds, selectivity was not gained over the parent 3-hydroxymethyl compounds (1, 2) due to a loss in PNMT inhibitory potency. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：1143 / 1147

页数：5

共 29 条

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