| New cathepsin D inhibitor library utilizing hydroxyethyl isosteres with cyclic tertiary amines. | |
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MedLine Citation:
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PMID: 22830497 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The design and synthesis of hydroxyethylamine isosteres as inhibitors of cathepsin D based on SAR data have been accomplished. A library of 96 of these hydroxyethylamine isosteres are described and many have proven to be very potent inhibitors of human cathepsin D activity as measured using a fluorometric assay technique, via peptide substrate Ac-Glu-Glu(Edans)-Lys-Pro-Ile-Cys-Phe-Phe-Arg-Leu-Gly-Lys(Methyl Red)-Glu-NH(2). Compounds showing strongest inhibition of cathepsin D activity were those that contain a hydroxyethyl-N'-2- or N'-(4-chlorophenyl)piperazine moiety (IC(50) values range from 0.55 to 8.5 nM), with N'-(2-pyrimidyl)piperizine (IC(50) values range from 0.5 to 21.6 nM), with N-N'- L-piperazinocolinamide (IC(50) values range from 0.001 - 0.25 nM), or N-N'-L-piperazinocolin-N-methylamide (IC(50) values range from 0.015 - 7.3 nM). |
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Authors:
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Rose M McConnell; Kalyani Inapudi; Naveen Kadasala; Karthika Yarlagadda; Priya Velusamy; Matthew S McConnell; Adam Green; Carol Trana; Kelley Sayyar; James S McConnell |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Medicinal chemistry (Shāriqah (United Arab Emirates)) Volume: 8 ISSN: 1875-6638 ISO Abbreviation: Med Chem Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-10-24 Completed Date: 2013-04-04 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 101240303 Medline TA: Med Chem Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1146-54 Citation Subset: IM |
Affiliation:
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Department of Chemistry, Western Illinois University, Macomb, IL 61455, USA. RM-McConnell@wiu.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amines
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chemistry*,
pharmacology* Cathepsin D / antagonists & inhibitors* Humans Inhibitory Concentration 50 Liver / enzymology Protease Inhibitors / chemistry*, pharmacology* Small Molecule Libraries / chemistry*, pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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3R15 CA086933-04/CA/NCI NIH HHS; 3R15CA086933-04A2S1/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amines; 0/Protease Inhibitors; 0/Small Molecule Libraries; EC 3.4.23.5/Cathepsin D |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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