Author/Authors :
Richard G. Wilde، نويسنده , , Jeffrey T. Billheimer، نويسنده , , Sandie J. Germain، نويسنده , , Elizabeth A. Hausner، نويسنده , , Paul C. Meunier، نويسنده , , Deborah A. Munzer، نويسنده , , Janet K. Stoltenborg، نويسنده , , Peter J. Gillies، نويسنده , , Deborah L. Burcham، نويسنده , , Shiew-Mai Huang، نويسنده , , John D. Klaczkiewicz، نويسنده , , Soo S. Ko، نويسنده , , Ruth R. Wexler، نويسنده ,
Abstract :
Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesterol esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.
Keywords :
thioaldehyde , Cycloaddition , Atherosclerosis , acyl-CoA:cholesterol acyltransferase
