Acyl CoA:Cholesterol Acyltransferase (ACAT) Inhibitors: Synthesis and Structure-Activity Relationship Studies of a New Series of Trisubstituted Imidazoles
| Autor: | Peter J. Gillies, C. Anne Higley, Pennio Pennev, Alexander L. Johnson, Candy S. Robinson, Richard G. Wilde, Thomas P. Maduskuie, Jeffrey T. Billheimer, Ruth R. Wexler |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Stereochemistry Sterol O-acyltransferase Thio Structure-Activity Relationship In vivo Cricetinae Drug Discovery Animals Urea Structure–activity relationship IC50 chemistry.chemical_classification Mesocricetus Molecular Structure biology Anticholesteremic Agents Imidazoles In vitro Rats Cholesterol Enzyme Biochemistry chemistry Enzyme inhibitor Microsomes Liver biology.protein Molecular Medicine Sterol O-Acyltransferase |
| Zdroj: | Journal of Medicinal Chemistry. 37:3511-3522 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00047a009 |
| Popis: | A series of 4,5-diaryl-2-(substituted thio)-1H-imidazoles has been synthesized and demonstrated to be potent inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). The design, synthesis, and structure-activity relationships for this series are reported herein. One of the compounds from this series, N'-(2,4-difluorophenyl)-N-[5-[(4,5-diaryl-1H-imidazol-2- yl)thio]pentyl]-N-heptylurea (DuP 128), was selected for development as an intestinally active ACAT inhibitor. DuP 128 is a potent ACAT inhibitor in vitro and in vivo, inhibiting ACAT in rat hepatic microsomes with an IC50 = 10 nM and possessing potent antihypercholesterolemic activity in vivo. |
| Databáze: | OpenAIRE |
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