| Progresses in the pursuit of aldose reductase inhibitors: The structure-based lead optimization step. | |
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MedLine Citation:
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PMID: 22436396 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Aldose reductase (ALR2) is a crucial enzyme in the development of the major complications of diabetes mellitus. Very recently it has been demonstrated that the ARL2 inhibitor, fidarestat, significantly prevents inflammatory signals (TNF-α, LPS) that cause cancer (colon, breast, prostate and lung), metastasis, asthma, and other inflammatory diseases. Currently, fidarestat is in phase III clinical trial for diabetic neuropathy and was found to be safe. Thus the finding of novel, potent ARL2 inhibitors is today more than in the past in great demand as they can pave the way for a novel therapeutic approach for a number of diseases besides the diabetes. Herein, starting from the virtual screening-derived ALR2 inhibitor S12728 (1), a rational receptor-based lead optimization has been undertaken. The design and synthetic efforts here reported led to the discovery of several new compounds endowed with low micromolar/submicromolar activities. |
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Authors:
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Anna Ramunno; Sandro Cosconati; Stefania Sartini; Vita Maglio; Sara Angiuoli; Valeria La Pietra; Salvatore Di Maro; Mariateresa Giustiniano; Concettina La Motta; Federico Da Settimo; Luciana Marinelli; Ettore Novellino |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-3-5 |
Journal Detail:
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Title: European journal of medicinal chemistry Volume: - ISSN: 1768-3254 ISO Abbreviation: - Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-3-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0420510 Medline TA: Eur J Med Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Elsevier Masson SAS. All rights reserved. |
Affiliation:
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Dipartimento di Scienze Farmaceutiche, Università di Salerno, Via Ponte Don Melillo 11c, 84084 Fisciano, Italy. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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