Substituted (1,2-Diarylethyl)amide Acyl-CoA:Cholesterol Acyltransferase Inhibitors: Effect of Polar Groups on in Vitro and in Vivo Activity
| Autor: | Dugar Sundeep, Robert E. Burrier, Brian G. Salisbury, Wayne Vaccaro, Joel G. Berger, Harry R. Davis, Timothy Kogan, John W. Clader, Martin S. Domalski |
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| Rok vydání: | 1995 |
| Předmět: |
Male
medicine.drug_class Stereochemistry Sterol O-acyltransferase Carboxamide Structure-Activity Relationship chemistry.chemical_compound In vivo Cricetinae Drug Discovery medicine Animals Moiety Mesocricetus biology Chemistry Anticholesteremic Agents Amides In vitro Biochemistry Enzyme inhibitor Microsomes Liver Microsome Cholesteryl ester biology.protein Molecular Medicine Sterol O-Acyltransferase |
| Zdroj: | Journal of Medicinal Chemistry. 38:1600-1607 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | Substituted (1,2-diarylethyl)amides have been prepared and evaluated for their ability to inhibit microsomal acyl-CoA:cholesterol acyltransferase activity in vitro and to lower hepatic cholesteryl ester content in vivo in a cholesterol-fed hamster. Simple unsubstituted (diarylethyl)amides were potent inhibitors in vitro but showed poor activity in vivo. Introduction of polar groups at specific locations on the diarylethylamine moiety decreased in vitro activity but increased in vivo activity. Both effects were highly structure dependent, suggesting specific interactions which were mediating activity in each model. Optimization of these opposing effects led to compounds which were potent in both models. |
| Databáze: | OpenAIRE |
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