Polyunsaturated fatty acid anilides as inhibitors of acyl-coA: cholesterol acyltransferase (ACAT).
A series of polyunsaturated fatty acid anilides were synthesized and evaluated as ACAT inhibitors. Compound 24 had potent inhibitory activity against microsomal ACAT derived from U937, HepG2 and Caco-2 cell lines. Therefore, it might be expected to act as an antiarteriosclerotic and hypocholesterolemic agent. Interestingly, the ACAT inhibitory potency of 24 varied significantly depending on the source of the enzyme.
Matsuyama
N
N
R & D Facilities, Azwell Inc., Osaka, Japan.
Kosaka
T
T
Fukuhara
M
M
Soda
Y
Y
Mizuno
K
K
D000311:Adrenal Glands / Q000201:enzymology; D000813:Anilides / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002460:Cell Line; D004281:Docosahexaenoic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D015118:Eicosapentaenoic Acid / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007422:Intestines / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D011817:Rabbits; D013045:Species Specificity; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
D000813:Anilides; D000924:Anticholesteremic Agents; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; C121287:N-(2,6-diisopropylphenyl)-4,7,10,13,16,19-docosahexaenamide; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D002785:Sterol O-Acyltransferase