ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes
摘要:
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. Copyright (C) 1996 The DuPont Merck Pharmaceutical Company.
2,3-Dialkyl-1,3-butadienes were selectively synthesized by the copper(I) iodide-catalyzed reaction of 1,4-bis-[diethoxyphosphinyloxy]-2-butyne with alkyl Grignard reagents.
A facile method for the preparation of functionalized 2,3-disubstituted-1,3-butadienes
作者:Lishan Zhu、Reuben D. Ricke
DOI:10.1016/0040-4039(91)80633-h
日期:1991.6
Functionalized 2,3-disubstituted-1,3-butadienes were readily prepared by reacting functionalized organozinc compounds with 1,4-dichloro-2-butyne or 1,4-ditosyloxy-2-butyne mediated by Cu(I) salts.
ARAKI, SHUKI;OHMURA, MASAYUKI;BUTSUGAN, YASUO, SYNTHESIS, BRD, 1985, N 10, 963-964