Cholody W M, Martelli S, Konopa J
Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdansk, Poland.
J Med Chem. 1992 Jan 24;35(2):378-82. doi: 10.1021/jm00080a026.
The synthesis of 8-hydroxy and 8-methoxy analogues of some substituted 5-aminoimidazoacridinones (4) is described. The synthesis was carried out by a three-step sequence from the corresponding 1-chloro-4-nitro-9(10H)-acridinone precursors (1). The annulation of the imidazolo ring onto the aminoacridinone chromophore was accomplished by heating the required aminoacridinone (3) with formic acid or, in the case of 1-methyl derivatives, with N,N-dimethylacetamide. Potent cytotoxic activity against L1210 leukemia, as well as antitumor activity against P388 leukemia in mice, was demonstrated for the 8-hydroxy analogues. The corresponding 8-methoxy derivatives were not cytotoxic. However, in some cases, they showed significant in vivo antileukemic activity.
描述了一些取代的5-氨基咪唑并吖啶酮（4）的8-羟基和8-甲氧基类似物的合成。该合成由相应的1-氯-4-硝基-9（10H）-吖啶酮前体（1）通过三步序列进行。通过将所需的氨基吖啶酮（3）与甲酸加热，或者在1-甲基衍生物的情况下与N，N-二甲基乙酰胺加热，将咪唑环环合到氨基吖啶酮发色团上。8-羟基类似物对L1210白血病显示出强细胞毒性活性，以及对小鼠P388白血病的抗肿瘤活性。相应的8-甲氧基衍生物没有细胞毒性。然而，在某些情况下，它们显示出显著的体内抗白血病活性。
