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Structure-activity relationship of human glutaminyl cyclase inhibitors having an N-(5-methyl-1H-imidazol-1-yl)propyl thiourea template.

Abstract：

:In an effort to design inhibitors of human glutaminyl cyclase (QC), we have synthesized a library of N-aryl N-(5-methyl-1H-imidazol-1-yl)propyl thioureas and investigated the contribution of the aryl region of these compounds to their structure-activity relationships as cyclase inhibitors. Our design was guided by the proposed binding mode of the preferred substrate for the cyclase. In this series, compound 52 was identified as the most potent QC inhibitor with an IC50 value of 58 nM, which was two-fold more potent than the previously reported lead 2. Compound 52 is a most promising candidate for future evaluation to monitor its ability to reduce the formation of pGlu-Aβ and Aβ plaques in cells and transgenic animals.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Tran PT,Hoang VH,Thorat SA,Kim SE,Ann J,Chang YJ,Nam DW,Song H,Mook-Jung I,Lee J,Lee J

doi

10.1016/j.bmc.2013.04.005

subject

Has Abstract

pub_date

2013-07-01 00:00:00

pages

3821-30

issue

13

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(13)00322-2

journal_volume

21

pub_type

杂志文章

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