1025828-97-0Relevant academic research and scientific papers
Novel aryloxyalkylthioimidazoles as inhibitors of acyl-CoA: Cholesterol-O-acyltransferase
Bani,Bormetti,Ceccarelli,Fiocchi,Gobetti,Lombroso,Magnetti,Olgiati,Palladino,Villa,Vanotti
, p. 39 - 46 (2007/10/02)
A series of aryloxyalkcylthioimidazoles have been synthesized and evaluated for their ability to interfere with the enzyme acyl-CoA (cholesterol-O-acyltransferase) (ACAT, EC 2.3.1.26). Most of the molecules possessed a good in vitro ACAT inhibitory activity with IC50 values ranging between 0.1 and 2.0 μM. Some of them, eg, 2-{5-[(4-isobutoxycarbonyl)phenoxy]pentylthio} -4,5-diphenylimidazole 13, 2- {3-[(4-isobutoxycarbonyl)phenoxy]-2-oximopropylthio} -4,5-diphenylimidazole 21, 2-{3-[(4-isobutoxycarbonyl)phenoxy]-2-hydrazonecarboxamidepropylthio}-4,5 -diphenylimidazole 26, 2-[5-(2-pyridoxy)-pentylthio]-4,5-dipilenylimidazole 40 and 2-{5-[(3,5-diterbutyl-4-hydroxy)phenylthiolpentylthio}-4,5-diphenylimidazole 42, were more potent (range of activity 10-90 nM). They were also more potent with respect to the reference CI-976. When administered orally in hyperlipemic rats, at 10 and 50 mg/kg doses, some representative compounds, like 2-{3-[(4-isobutoxycarbonyl)phenoxy]-2-hydroxypropylthio}-4,5 -diphenylimidazole 1, 13 and 26, reduced VLDL/LDL-associated cholesterol levels by 30-50% and increased HDL cholesterol levels by 15-50%. In addition, liver accumulation of esterified cholesterol was counteracted (50-80% reduction) and liver ACAT ex vivo activity was decreased by 70-85%. Finally, the good efficacy displayed in an endogenous model of hypertriglyceridemia strongly supports the hypothesis of a good systemic availability, which constitutes one of the principal properties of a valuable ACAT inhibitor.
8-Substituted purine derivatives: a new class of lipid-lowering agents
Vanotti, E.,Bani, M.,Favara, D.,Gobetti, M.,Lombroso, M.,et al.
, p. 287 - 294 (2007/10/02)
A series of purine derivatives have been prepared and their in vivo abilities to lower plasma total cholesterol and triglyceride levels, and to elevate high density lipoprotein (HDL) cholesterol levels in hyperlipemic rats have been tested.Some compounds, among which 8-propylthio>adenosine 31, 8--2-oxopropylthio>adenosine 33 and 8--2-hydrazonecarboxamidepropylthio>adenosine 36 appear to be the most interesting, have been found to have both the desired profile of activity and no hepatotoxicity, when administered po at 50, 100 or 300 mg/kg.Compounds 31, 33 and 36, orally tested at the same doses in the 15-d test, lower triglyceride and VLDL/LDL (very low density lipoprotein / low density lipoprotein) cholesterol levels by 10-33percent and 13-46percent, respectively, and increase HDL-associated cholesterol levels by 10-32percent.These molecules have been chosen for further pharmacological and toxicological evaluations. adenosine / purine / cholesterol / triglyceride / hypolipemic agent
