Document Detail

New cathepsin D inhibitor library utilizing hydroxyethyl isosteres with cyclic tertiary amines.
MedLine Citation:
PMID:  22830497     Owner:  NLM     Status:  MEDLINE    
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).
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:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Medicinal chemistry (Shāriqah (United Arab Emirates))     Volume:  8     ISSN:  1875-6638     ISO Abbreviation:  Med Chem     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-24     Completed Date:  2013-04-04     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  101240303     Medline TA:  Med Chem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1146-54     Citation Subset:  IM    
Department of Chemistry, Western Illinois University, Macomb, IL 61455, USA.
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MeSH Terms
Amines / chemistry*,  pharmacology*
Cathepsin D / antagonists & inhibitors*
Inhibitory Concentration 50
Liver / enzymology
Protease Inhibitors / chemistry*,  pharmacology*
Small Molecule Libraries / chemistry*,  pharmacology*
Grant Support
3R15 CA086933-04/CA/NCI NIH HHS; 3R15CA086933-04A2S1/CA/NCI NIH HHS
Reg. No./Substance:
0/Amines; 0/Protease Inhibitors; 0/Small Molecule Libraries; EC D

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