Document Detail

Recent advances in the medicinal chemistry of alpha-aminoboronic acids, amine-carboxyboranes and their derivatives.
MedLine Citation:
PMID:  15544560     Owner:  NLM     Status:  MEDLINE    
This article describes recent developments in the synthesis and biological activity of alpha-aminoboronic acids, amine-carboxyboranes and their derivatives as potential therapeutic agents. alpha-Amino acid analogues are of considerable interest as inhibitors of enzymes involved in amino acid and peptide metabolism. In particular, alpha-amino alkylphosphonic acids and alpha-amino alkylboronic acids, in which the carboxyl group of amino acids is replaced by a phosphonic acid or boronic acid function, respectively, constitute a unique class of amino acid mimics from which a number of potent enzyme inhibitors have been synthesized. The inhibitory activity mainly stems from the fact that the tetrahedral phosphonic moiety or the tetrahedral adduct of electrophilic boronic acid is a good mimic of the putative tetrahedral transition state or intermediate encountered in the enzymatic hydrolysis or formation of peptides. Since the peptide hydrolysis and formation invariably involves the tetrahedral high energy species in the course of the reaction, these amino acid mimics serve as a general key element for inhibitors of a broad spectrum of proteases and peptide ligases. Serine protease inhibitors provide promising compounds having a P site binding moiety and a boronic acid chelating moiety. The compounds have been shown to have high inhibitory activity.
Valery M Dembitsky; Abed Al Aziz Quntar; Morris Srebnik
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Mini reviews in medicinal chemistry     Volume:  4     ISSN:  1389-5575     ISO Abbreviation:  Mini Rev Med Chem     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-11-16     Completed Date:  2005-02-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  101094212     Medline TA:  Mini Rev Med Chem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1001-18     Citation Subset:  IM    
Department of Medicinal Chemistry and Natural Products, School of Pharmacy, P.O. Box 12065, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
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MeSH Terms
Boranes / chemistry*,  pharmacology*
Boronic Acids / chemistry*,  pharmacology*
Enzyme Inhibitors / chemistry,  pharmacology
Serine Endopeptidases / metabolism
Structure-Activity Relationship
Reg. No./Substance:
0/Boranes; 0/Boronic Acids; 0/Enzyme Inhibitors; EC 3.4.21.-/Serine Endopeptidases

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