Document Detail

Effect of C7 Modifications on Benzothiadiazine-1,1-dioxide Derivatives on Their Inhibitory Activity and Selectivity toward Aldose Reductase.
MedLine Citation:
PMID:  23136050     Owner:  NLM     Status:  Publisher    
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.
Shuzhen Zhang; Xin Chen; Shagufta Parveen; Saghir Hussain; Yanchun Yang; Chaojun Jing; Changjin Zhu
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-7
Journal Detail:
Title:  ChemMedChem     Volume:  -     ISSN:  1860-7187     ISO Abbreviation:  ChemMedChem     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101259013     Medline TA:  ChemMedChem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Department of Applied Chemistry, Beijing Institute of Technology, Zhongguancun South Street, 100081 Beijing (China).
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