| Effect of C7 Modifications on Benzothiadiazine-1,1-dioxide Derivatives on Their Inhibitory Activity and Selectivity toward Aldose Reductase. | |
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MedLine Citation:
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PMID: 23136050 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The development and progression of chronic complications in diabetic patients, such as retinopathy, nephropathy, neuropathy, cataracts, and stroke, are related to the activation and/or overexpression of aldose reductase (ALR2), which is a member of the aldo-keto reductase superfamily. A structure-activity relationship study focused on the C7 position of 1,2,4-benzothiadiazine-1,1-dioxide derivatives was pursued in an attempt to discover ALR2 inhibitors with enhanced potency and selectivity. These studies led to a series of new C7-substituted compounds, which were evaluated for their inhibitory activity against ALR2; they exhibited IC(50) values in the range of 2.80-45.13 nM. Two compounds with a C7-dimethylcarbamoyl and a C7-diethylcarbamoyl substituent, respectively, were found to be the most active and presented excellent selectivity for ALR2 over aldehyde reductase (ALR1). The structure-activity relationship analyses and molecular modeling studies presented herein highlight the importance of hydrophobic and bulky groups at the C7 position for inhibitory activity and selectivity toward ALR2. |
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Authors:
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Shuzhen Zhang; Xin Chen; Shagufta Parveen; Saghir Hussain; Yanchun Yang; Chaojun Jing; Changjin Zhu |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-7 |
Journal Detail:
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Title: ChemMedChem Volume: - ISSN: 1860-7187 ISO Abbreviation: ChemMedChem Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101259013 Medline TA: ChemMedChem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Affiliation:
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Department of Applied Chemistry, Beijing Institute of Technology, Zhongguancun South Street, 100081 Beijing (China). |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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