Delarue S, Girault S, Dali Ali F, Maes L, Grellier P, Sergheraert C
UMR CNRS 8525, Institut de Biologie et Institut Pasteur de Lille, Faculté de Pharmacie, Université de Lille II, France.
Chem Pharm Bull (Tokyo). 2001 Aug;49(8):933-7. doi: 10.1248/cpb.49.933.
Amodiaquine (AQ) is an antimalarial which is effective against chloroquino-resistant strains of Plasmodium falciparum but whose clinical use is severely restricted because of associated hepatotoxicity and agranulocytosis. "One-pot" synthesis of formamidines likely to be transformed into AQ derivatives is reported. Compared with AQ, the new compounds were devoid of in vitro cytotoxicity upon human embryonic lung cells and mouse peritoneal macrophages. One showed a potent in vivo activity in mice infected with P berghei. Transformation of this compound by reductive amination led to a new type of AQ derivatives that displayed an in vitro activity similar to that of AQ but did not lead to toxic quinone-imines.
阿莫地喹（AQ）是一种抗疟药，对恶性疟原虫的氯喹耐药菌株有效，但由于其相关的肝毒性和粒细胞缺乏症，其临床应用受到严重限制。本文报道了可能转化为AQ衍生物的甲脒的“一锅法”合成。与AQ相比，新化合物对人胚肺细胞和小鼠腹腔巨噬细胞无体外细胞毒性。其中一种化合物在感染伯氏疟原虫的小鼠中显示出强大的体内活性。通过还原胺化将该化合物转化，得到了一种新型的AQ衍生物，其体外活性与AQ相似，但不会产生有毒的醌亚胺。
