Ohnuma Satoshi, Muraoka Masami, Ioriya Katsuhisa, Ohashi Naohito
Research Division, Sumitomo Pharmaceuticals Co. Ltd, 1-98 Kasugade Naka 3-chome, Konohana-ku, Osaka 554-0022, Japan.
Bioorg Med Chem Lett. 2004 Mar 8;14(5):1309-11. doi: 10.1016/j.bmcl.2003.12.045.
The synthesis and structure-activity relationships of N-phenyl-N'-[3-(4-phenylnaphthylidinoyl)]urea derivatives 3 as a novel structural class of potent ACAT inhibitors is described. A 3-methoxy group substituted on the naphthylidinone 4-phenyl ring, together with a 1-N-(n)butyl substitution, SM-32504 (3m), gave a potent ACAT inhibitor, in vitro, respectively. The most potent compound, SM-32504 (3m), decreased the serum cholesterol level significantly in a high fat and high cholesterol-fed mouse model.
描述了作为新型强效ACAT抑制剂结构类别的N-苯基-N'-[3-(4-苯基萘啶甲酰基)]脲衍生物3的合成及其构效关系。在萘啶酮的4-苯基环上取代一个3-甲氧基，再加上1-N-(正)丁基取代，即SM-32504(3m)，分别在体外产生了一种强效ACAT抑制剂。最有效的化合物SM-32504(3m)在高脂肪和高胆固醇喂养的小鼠模型中显著降低了血清胆固醇水平。
