| 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. | |
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MedLine Citation:
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PMID: 22104435 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2011-11-3 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry Volume: - ISSN: 1464-3391 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9413298 Medline TA: Bioorg Med Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Hospital Pharmacy, University of Toyama, Toyama 930-0194, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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