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Managing the Liabilities Arising from Structural Alerts: A Safe Philosophy for Medicinal Chemists.
MedLine Citation:
PMID:  21651480     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Bioactivation of xenobiotics can, in certain circumstances, result in the formation of reactive electrophilic species. These reactive metabolites may covalently modify proteins and macromolecules and it has been suggested that protein modification is a key initial step in provoking idiosyncratic adverse drug reactions. Understanding these bioactivation pathways is critical in order to rationally design drug candidates with a lower propensity to form reactive intermediates. Herein, we provide an overview of the importance of Structural Alerts and bioactivation pathways and describe the creation of an in-house database as a tool aimed at informing medicinal chemists about these potential liabilities.
Authors:
P J Edwards; C Sturino
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-8
Journal Detail:
Title:  Current medicinal chemistry     Volume:  -     ISSN:  1875-533X     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9440157     Medline TA:  Curr Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Boehringer Ingelheim (Canada) Limited, 2100 Cunard Street, Laval (Québec), H7S 2G5, Canada. paul.edwards@boehringer-ingelheim.com.
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