d'Atri G, Gomarasca P, Resnati G, Tronconi G, Scolastico C, Sirtori C R
J Med Chem. 1984 Dec;27(12):1621-9. doi: 10.1021/jm00378a016.
New compounds were synthesized by changing the substituents of a trisubstituted pyrimidine, i.e., [[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]thio] acetic acid, a potent hypolipidemic agent, impaired, however, by a marked hepatomegaly-inducing effect. The structural variations led to the subsidence (14b, i.e., 4-chloro-2-(dimethylamino)-6-[(2,3-dimethylphenyl)amino]pyrimidine) or to the reduction (18b, [[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]amino] acetic acid) of said untoward effect but still maintained the hypolipidemic effect that, although markedly decreased, still proves significant for serum cholesterol and triglycerides (18b) or for serum triglycerides only (14b).
通过改变三取代嘧啶的取代基合成了新化合物,即[[4-氯-6-[(2,3-二甲基苯基)氨基]-2-嘧啶基]硫代]乙酸,一种有效的降血脂剂,但因显著的肝肿大诱导作用而受到损害。结构变化导致上述不良作用的减轻(14b,即4-氯-2-(二甲基氨基)-6-[(2,3-二甲基苯基)氨基]嘧啶)或降低(18b,[[4-氯-6-[(2,3-二甲基苯基)氨基]-2-嘧啶基]氨基]乙酸),但仍保持降血脂作用,尽管该作用显著降低,但对血清胆固醇和甘油三酯(18b)或仅对血清甘油三酯(14b)仍具有显著意义。