Document Detail

Aminoacyl-tRNA synthetase inhibitors as antimicrobial agents: a patent review from 2006 till present.
MedLine Citation:
PMID:  23062029     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Aminoacyl-tRNA synthetases (aaRSs) are one of the leading targets for development of antimicrobial agents. Although these enzymes are well conserved among prokaryotes, significant divergence has occurred between prokaryotic and eukaryotic aaRSs, which can be exploited in the discovery of broad-spectrum antibacterial agents. Although several aaRS inhibitors have been reported before, they failed as a result of poor selectivity and limited cell penetration.
AREAS COVERED: This review covers January 2006 to April 2012 wherein several new analogues were claimed as aaRS inhibitors. Anacor Pharmaceuticals patented several boron-containing derivatives inhibiting the function of the editing domain of aaRSs. Two patents describe the combination of aaRS inhibitors with other antibacterial agents. Patents disclosing aaRS inhibitors for indications other than antimicrobial agents are not considered for review here.
EXPERT OPINION: Several recently disclosed leads may form the foundation for development of potent and selective bacterial aaRS inhibitors. In comparison with, for example, terbinafine and itraconazole, compound C10 (AN2690) is a very promising candidate for treatment of ungual and periungual infections with improved nail penetration and low keratin binding. In addition, Raplidyne, Inc. reported bicyclic heteroaromatic compounds as potent and selective inhibitors of bacterial MetRS. These have proven to be particularly effective for treatment of Clostridium difficile-associated diarrhea. Finally, combination of aaRS inhibitors to attenuate resistance looks as a viable strategy to expand the lifespan of existing antibiotics.
Bharat Gadakh; Arthur Van Aerschot
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2012-10-12
Journal Detail:
Title:  Expert opinion on therapeutic patents     Volume:  22     ISSN:  1744-7674     ISO Abbreviation:  Expert Opin Ther Pat     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-20     Completed Date:  2013-05-10     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  9516419     Medline TA:  Expert Opin Ther Pat     Country:  England    
Other Details:
Languages:  eng     Pagination:  1453-65     Citation Subset:  IM    
KU Leuven, Rega Institute for Medical Research, Laboratory of Medicinal Chemistry, Minderbroedersstraat 10, 3000 Leuven, Belgium.
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MeSH Terms
Amino Acyl-tRNA Synthetases / antagonists & inhibitors*,  metabolism
Anti-Bacterial Agents / chemistry,  pharmacology*,  therapeutic use
Bacteria / drug effects*,  enzymology,  growth & development
Bacterial Infections / drug therapy,  microbiology
Drug Design*
Enzyme Inhibitors / chemistry,  pharmacology*,  therapeutic use
Molecular Structure
Patents as Topic*
Protein Conformation
Structure-Activity Relationship
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Enzyme Inhibitors; EC 6.1.1.-/Amino Acyl-tRNA Synthetases

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