Document Detail


Synthesis and structure-activity relationship of 4-substituted benzoic acids and their inhibitory effect on the biosynthesis of fatty acids and sterols.
MedLine Citation:
PMID:  15818566     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The synthesis of 4-[3-(substituted phenyl)-2-oxo-5-oxazolidinyl]methoxybenzoic acids and their inhibitory effects on the biosynthesis of fatty acids and sterols is described. IC50 values in vitro were 10(-6) and 10(-5) M, respectively. Though the in vitro inhibitory activity of all these compounds toward sterol biosynthesis was inferior to that of pravastatin, several compounds had a stronger reducing effect in Sprague-Dawley (SD) rat on both, cholesterol (TC) and triglyceride (TG), than pravastatin and bezafibrate. The potent compounds were present at high concentrations in rat liver. The enantiomers of the potent racemic compounds (4-[3-(4-bromo-2-fluorophenyl)-2-oxo-5-oxazolidinyl]methoxybenzoic acid) were prepared and their activity was examined in vivo and in vitro. In vivo, each enantiomer possessed more activity than the racemic compound. Further, in Watanabe hereditable hyperlipidemic (WHHL) rabbit, optically active (R)-4-[3-(4-bromo-2-fluorophenyl)-2-oxo-5-oxazolidinyl]methoxybenzoic acid also potently reduced the effect of both TC and TG on serum levels, compared with pravastatin and bezafibrate.
Authors:
Tomoyasu Ohno; Kazuo Ogawa; Shingo Yano; Masakazu Fukushima; Norihiko Suzuki; Tetsuji Asao
Related Documents :
12737406 - Synthesis and antimicrobial activities of some isocoumarin and dihydroisocoumarin deriv...
20573426 - Synthesis and preliminary bioactivity assays of 3,4-dichloro-5-(omega-hydroxyalkylamino...
2930626 - Quinazoline antifolates inhibiting thymidylate synthase: computer modelling of the n10 ...
10863796 - Benzimidazoles as nmda glycine-site antagonists: study on the structural requirements i...
134866 - A sensitive automated procedure for the determination of glucuronic acid.
23994306 - One-step production of biodiesel from rice bran oil catalyzed by chlorosulfonic acid mo...
Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article    
Journal Detail:
Title:  Archiv der Pharmazie     Volume:  338     ISSN:  0365-6233     ISO Abbreviation:  Arch. Pharm. (Weinheim)     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-05-09     Completed Date:  2005-07-11     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0330167     Medline TA:  Arch Pharm (Weinheim)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  147-58     Citation Subset:  IM    
Affiliation:
Hanno Research Center, Taiho Pharmaceutical Co. Ltd., Hanno, Japan. tom-ohno@taiho.co.jp
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Benzoic Acids / chemical synthesis*,  pharmacology*
Chemistry, Physical
Cholesterol / biosynthesis
Depression, Chemical
Fatty Acids / biosynthesis*
Liver / drug effects,  metabolism
Male
Physicochemical Phenomena
Rabbits
Rats
Rats, Sprague-Dawley
Sterols / biosynthesis*
Structure-Activity Relationship
Triglycerides / blood
Chemical
Reg. No./Substance:
0/Benzoic Acids; 0/Fatty Acids; 0/Sterols; 0/Triglycerides; 57-88-5/Cholesterol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Reduction of Cr(VI) by immobilized cells of Desulfovibrio vulgaris NCIMB 8303 and Microbacterium sp....
Next Document:  Using the diphosphanyl radical as a potential spin label: effect of motion on the EPR spectrum of an...