Acipimox (5-methylpyrazinecarboxylic acid 4-oxide) is a new lipolysis inhibitor that has a distant chemical relationship with nicotinic acid (NA). The tritiated compound (100 mg) is rapidly absorbed, peak plasma radioactivity being reached after 2 hr, with an almost total elimination unchanged in urine. A comparison of th antilipolytic activity of three doses of acipimox and three doses of NA showed acipimox to be 20 times as potent as NA. There was a correlation between intensity and duration of effect for acipimox, but not for NA. Plasma acipimox levels correlated with inhibition of lipolysis. In consideration of the very good subjective tolerability of acipimox at all doses tested, this drug may be suitable for control of lipolysis in hyperlipidemias.

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Inhibitors of the enzyme Acyl-CoA: Cholesterol Acyltransferase are regarded as potentially useful agents in the treatment of hypercholesterolemia and atherosclerosis. We report here a novel series of 2, 6-disubstituted-3-imidazolylbenzopyrane derivatives with significant in vitro ACAT inhibitory activity (IC50 range 0.05-0.5 microM). Compounds of this series such as 26 are examples of a new, structurally distinct class of potent ACAT inhibitors with high specificity for the aortic subtype of the enzyme. The structure-activity relationships of the 3-imidazolylbenzopyrane ACAT inhibitors were investigated by systematic manipulation of two regions of the parent compound 1 and the inhibitory activity resulted linked to the substituent in position 6 of the benzopyrane ring and modulated by the size of lipophilic substituents in position 2. Investigation of the mechanism of the inhibitory effect leads to the conclusion that these compounds act in a non-competitive fashion.

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