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    
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.
Tomoyasu Ohno; Kazuo Ogawa; Shingo Yano; Masakazu Fukushima; Norihiko Suzuki; Tetsuji Asao
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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    
Hanno Research Center, Taiho Pharmaceutical Co. Ltd., Hanno, Japan.
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MeSH Terms
Benzoic Acids / chemical synthesis*,  pharmacology*
Chemistry, Physical
Cholesterol / biosynthesis
Depression, Chemical
Fatty Acids / biosynthesis*
Liver / drug effects,  metabolism
Physicochemical Phenomena
Rats, Sprague-Dawley
Sterols / biosynthesis*
Structure-Activity Relationship
Triglycerides / blood
Reg. No./Substance:
0/Benzoic Acids; 0/Fatty Acids; 0/Sterols; 0/Triglycerides; 57-88-5/Cholesterol

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