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N-phenylpiperazine derivatives with hypocholesterolemic activity
Journal of Medicinal Chemistry
|June 1, 1985
Summary
New dioxolone compounds demonstrated significant plasma cholesterol-lowering activity in rats, with two compounds showing greater potency than clofibrate. Compound 8 (LR-19,731) is advancing to clinical trials for its hypolipemic effects.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Drug Discovery
Background:
- Dyslipidemia is a major risk factor for cardiovascular diseases.
- Novel therapeutic agents are needed to effectively manage lipid profiles.
- Piperazine derivatives have shown potential in modulating lipid metabolism.
Purpose of the Study:
- To synthesize and evaluate novel piperazine-containing compounds for hypolipemic activity.
- To identify potent cholesterol-lowering agents.
- To select lead compounds for further preclinical and clinical development.
Main Methods:
- Synthesis of 4-(4-phenyl-1-piperazinyl)-1-(4-fluorophenyl)-2-(acyloxy)-1-butanones and 4-aryl-5-[omega-(4-aryl-1-piperazinyl)alkyl]-1,3-dioxol-2-ones.
- Preliminary in vivo testing for hypolipemic activity in normal rats.
- Comparative analysis of efficacy against clofibrate.
Main Results:
- Several synthesized dioxolone derivatives exhibited significant plasma cholesterol-lowering effects.
- Two dioxolone compounds (6 and 8) demonstrated superior potency compared to clofibrate.
- Compound 8, 4-(4-Chlorophenyl)-5-[2-(4-phenyl-1-piperazinyl)ethyl]-1,3-dioxol-2-one (LR-19,731), was identified as a highly active agent.
Conclusions:
- The novel dioxolone derivatives possess promising hypolipemic properties.
- Compound 8 (LR-19,731) shows significant potential as a therapeutic agent for dyslipidemia.
- Compound 8 has been selected for progression into clinical trials.