SYNTHESIS AND HYPOLIPIDEMIC ACTIVITY OF 4-SUBSTITUTED 1-ACYL-1,2,4-TRIAZOLIDINE-3,5-DIONES IN RODENTS

A series of 4-substituted 1-acyl-1,2,4-triazolidine-3,5-diones demonstrated potent activity in CF1 mice when administered intraperitoneally at 20 mg/kg/day, lowering both serum cholesterol and triglyceride levels significantly. The 4-(4-chlorophenyl)-substituted compounds demonstrated better hypolip...

Full description

Saved in:
Bibliographic Details
Published inJournal of pharmaceutical sciences Vol. 82; no. 4; pp. 408 - 415
Main Authors SIMLOT, R, IZYDORE, RA, WONG, OT, HALL, IH
Format Journal Article
LanguageEnglish
Published NEW YORK Elsevier 01.04.1993
Subjects
Animals
Chemistry
Chemistry, Medicinal
Chemistry, Multidisciplinary
Hypolipidemic Agents - chemical synthesis
Hypolipidemic Agents - chemistry
Hypolipidemic Agents - pharmacology
Life Sciences & Biomedicine
Lipids - biosynthesis
Lipids - blood
Lipoproteins - blood
Liver - enzymology
Male
Mice
Pharmacology & Pharmacy
Physical Sciences
Rats
Rats, Sprague-Dawley
Science & Technology
Structure-Activity Relationship
Triazoles - chemical synthesis
Triazoles - chemistry
Triazoles - pharmacology
PHOSPHATIDATE PHOSPHOHYDROLASE
INHIBITORS
CHOLESTEROL
DERIVATIVES
CITRATE
Online AccessGet more information

Cover

More Information
Summary:A series of 4-substituted 1-acyl-1,2,4-triazolidine-3,5-diones demonstrated potent activity in CF1 mice when administered intraperitoneally at 20 mg/kg/day, lowering both serum cholesterol and triglyceride levels significantly. The 4-(4-chlorophenyl)-substituted compounds demonstrated better hypolipidemic activity in rodents than 4-methoxy-, 4-nitro-, and 4-t-butylphenyl substitutions. Aryl and alkyl substitutions rather than benzoyl substitutions at position 4 demonstrated good hypocholesterolemic activity. Selected compounds were examined for the mode of action in rats in which serum cholesterol and triglyceride levels were reduced after administration of 20 mg/kg/day orally; tissue lipids were reduced after 14 days of administration, and bile and fecal lipids were increased by 44-250%. Serum lipoprotein levels were also modulated by the agents, with cholesterol levels in very low density lipoprotein and low density lipoprotein fractions being reduced by 2-57%. Cholesterol levels in the high density lipoprotein fraction were elevated by 94-341%. Activities of mouse hepatic enzymes were suppressed by the agents in a manner that suggested that the compounds interfere with de novo synthesis of lipids.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.2600820415