Design and synthesis of novel inhibitors of human kynurenine aminotransferase-I

被引：14

作者：

Akladios, Fady N. ^{[1
]}

Nadvi, Naveed A. ^{[1
,2
]}

Park, Joohong ^{[2
]}

Hanrahan, Jane R. ^{[1
]}

Kapoor, Vimal ^{[3
]}

Gorrell, Mark D. ^{[2
]}

Church, W. Bret ^{[1
]}

机构：

[1] Univ Sydney, Fac Pharm A15, Sydney, NSW 2006, Australia

[2] Univ Sydney, Sydney Med Sch, Centenary Inst, Sydney, NSW 2006, Australia

[3] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 04期

关键词：

Schizophrenia; Kynurenic acid; Kynurenine; Kynurenine aminotransferase-I; Phenyl hydrazones; Indole propionic acid; HUMAN BRAIN; SCHIZOPHRENIA; PURIFICATION;

D O I：

10.1016/j.bmcl.2011.12.138

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Herein we report 6-ethoxy-6-oxo-5-(2-phenylhydrazono) hexanoic acid and 3-(2-carboxyethyl)-1H-indole- 2-carboxylic acid derivatives as synthetically accessible leads for human kynurenine aminotransferase-I (KAT-I) inhibitors. In total, 12 compounds were synthesized and their biological activities were determined using the HPLC-UV based KAT-I inhibition assay. Of the 12 compounds synthesized, 10 were found to inhibit human KAT-I and the most active compound was found to be 5-(2-(4-chlorophenyl) hydrazono)-6-ethoxy-6-oxohexanoic acid (9a) with an IC50 of 19.8 mu M. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：1579 / 1581

页数：3

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