N-Imidazolyl-4-chromanones, N-imidazolyl-1-tetralones, and their alcohols as hypolipemic agents raising high-density lipoproteins
作者:Paolo Cozzi、Umberto Branzoli、Pier Paolo Lovisolo、Gaetano Orsini、Germano Carganico、Antonio Pillan、Augusto Chiari
DOI:10.1021/jm00153a016
日期:1986.3
3-(1-imidazolyl)chroman-4-ones and 2-(1-imidazolyl)-1-tetralones II, some of their alcohols, and some related compounds were synthesized and tested for hypolipidemic activity. Compounds II, bearing appropriate lipophilic substituents on the phenyl ring, strongly reduced total serum cholesterol while raising high-density lipoprotein cholesterol in diet-induced hypercholesterolemic rats. 3-(1-Imidazolyl)chroman-4-ols
合成了一系列3-(1-咪唑基)苯并二氢吡喃-4-酮和2-(1-咪唑基)-1-四氢萘酮II,它们的一些醇和一些相关化合物,并测试了其降血脂活性。在饮食诱导的高胆固醇血症大鼠中,在苯环上带有适当亲脂性取代基的化合物II大大降低了血清总胆固醇,同时提高了高密度脂蛋白胆固醇。对应于II的3-(1-咪唑基)苯并吡喃-4-醇和2-(1-咪唑基)-1-四醇保留了降血脂活性,同时除去了与咪唑相邻的羰基或羟基,得到了惰性化合物。尽管许多活性化合物显着增加了肝脏的重量,但作为模型研究的一种化合物是6-氯-3-(1-咪唑基)-2,3-二氢-4H-1-苯并吡喃-4-酮(5)引起的。没有过氧化物酶体增殖。化合物5和相应的醇40,作为酮和醇系列的代表,在降血脂正常大鼠中显示出显着的降血脂活性。在胆固醇生物合成中检测到的某些化合物抑制乙酸盐的掺入,但没有抑制HMG-CoA还原酶。选择5-溴-6-羟基-2-(1-咪唑基)-3