Document Detail

Design, synthesis, and biological evaluation of novel (1-thioxo-1,2,3,4-tetrahydro-β-carbolin-9-yl)acetic acids as selective inhibitors for AKR1B1.
MedLine Citation:
PMID:  22104435     Owner:  NLM     Status:  Publisher    
New substituted (1-thioxo-1,2,3,4-tetrahydro-β-carbolin-9-yl)acetic acids were designed as the inhibitor of AKR1B1 based upon the structure of rhetsinine, a minor alkaloidal component of Evodia rutaecarpa, and twenty derivatives were synthesized and evaluated. The most active compound of the series was (2-benzyl-6-methoxy-1-thioxo-1,2,3,4-tetrahydro-β-carbolin-9-yl)acetic acid (7m), which showed comparable inhibitory activity for AKR1B1 (IC(50)=0.15μM) with clinically used epalrestat (IC(50)=0.1μM). In the view of activity and selectivity, the most potent compound was (2-benzyl-6-carboxy-1-thioxo-1,2,3,4-tetrahydro-β-carbolin-9-yl)acetic acid (7t), which showed strong inhibitory effect (IC(50)=0.17μM) and very high selectivity for AKR1B1 against AKR1A1 (311:1) and AKR1B10 (253:1) compared with epalrestat.
Daisuke Minehira; Daisuke Takeda; Hirokazu Urata; Atsushi Kato; Isao Adachi; Xu Wang; Yuji Matsuya; Kenji Sugimoto; Mayuko Takemura; Satoshi Endo; Toshiyuki Matsunaga; Akira Hara; Jun Koseki; Kayo Narukawa; Shuichi Hirono; Naoki Toyooka
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-3
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  -     ISSN:  1464-3391     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Department of Hospital Pharmacy, University of Toyama, Toyama 930-0194, Japan.
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