Document Detail


Self-organizing molecular field analysis of NSAIDs: Assessment of pharmacokinetic and physicochemical properties using 3D-QSPkR approach.
MedLine Citation:
PMID:  22521372     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Non-steroidal anti-inflammatory drug (NSAID) induced gastrointestinal toxicity has attracted greater attention over the years. The development of NSAIDs having safer therapeutic profile depends on the better understanding of their mechanisms, physicochemical and pharmacokinetic properties. The present investigation is aimed at in silico three dimensional quantitative structure-pharmacokinetic relationship (3D-QSPkR) assessment of a group of NSAIDs using self-organizing molecular field analysis (SOMFA) approach. Two different statistically validated models for dissociation constant (pK(a)) and volume of distribution (V(d)) were obtained from SOMFA studies of 22 clinically active NSAIDs having diversity in structure. 3D-QSPkR models delivered useful information about the contribution of shape and electrostatic potential on pK(a) and V(d). The study illustrated the significance of structural variables in molecular architecture of NSAIDs especially etodolac for further optimization of ADMET properties with improved therapeutic profile.
Authors:
Honey; Suresh Thareja; Manoj Kumar; V R Sinha
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-29
Journal Detail:
Title:  European journal of medicinal chemistry     Volume:  -     ISSN:  1768-3254     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-4-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0420510     Medline TA:  Eur J Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Masson SAS. All rights reserved.
Affiliation:
Pharmaceutics Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Sector-14, Chandigarh 160014, India.
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