Abstract
Mono- and diphenylpyridazine ureido derivatives, structurally related to DuP 128, were synthesized and tested for their inhibitory activity against ACAT isolated from rat liver microsomes. Several compounds displayed ACAT inhibition in the micromolar range. The amino derivatives 4a-c were also tested against hACAT-1 and hACAT-2 isoforms. They retained the same trend shown in the previous assay. Modeling studies on representative terms were performed. Significant similarities between the geometrical features of the model DuP 128 and the most active pyridazine derivatives were observed.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetyl-CoA C-Acetyltransferase / antagonists & inhibitors*
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Acetyl-CoA C-Acetyltransferase / chemistry
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Animals
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Cell Line
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Humans
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In Vitro Techniques
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Microsomes, Liver / enzymology
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Models, Molecular
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Phenylurea Compounds / chemical synthesis*
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Phenylurea Compounds / chemistry
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Phenylurea Compounds / pharmacology
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Protein Isoforms / antagonists & inhibitors
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Pyridazines / chemical synthesis*
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Pyridazines / chemistry
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Pyridazines / pharmacology
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Rats
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Sterol O-Acyltransferase / antagonists & inhibitors*
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Sterol O-Acyltransferase / chemistry
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Sterol O-Acyltransferase 2
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Structure-Activity Relationship
Substances
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Phenylurea Compounds
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Protein Isoforms
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Pyridazines
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Sterol O-Acyltransferase
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ACAT1 protein, human
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Acetyl-CoA C-Acetyltransferase