叶酸氮杂同系物的合成。
Synthesis of aza homologues of folic acid.
作者信息
Martinelli J E, Chaykovsky M, Kisliuk R L, Gaumont Y
出版信息
J Med Chem. 1979 Jul;22(7):874-7. doi: 10.1021/jm00193a023.
Folic acid analogues containing an additional nitrogen atom between the phenyl ring and the carbonyl group of the side chain were synthesized. None of the compounds showed significant inhibitory activity against human lymphoblastic leukemia cells (CCRF-CEM) in culture or against Lactobacillus casei (ATCC 7469) growth. Against L1210 leukemia in mice, the aza homologue of folic acid, 4, and the aspartic acid analogue, 14, showed no increase in life span over control animals. These compounds were more toxic in vivo than the corresponding methotrexate analogues. Compound 4 supported the growth of Streptococcus faecium (ATCC 8043), and its tetrahydro derivative supported the growth of Pediococcus cerevisiae (ATCC 8081). These results strongly suggest that 4 can substitute for folate derivatives as cofactors for serine transhydroxymethylase, thymidylate synthetase, and dihydrofolate reductase.
合成了在苯环与侧链羰基之间含有一个额外氮原子的叶酸类似物。这些化合物在培养物中对人淋巴细胞白血病细胞（CCRF - CEM）或对干酪乳杆菌（ATCC 7469）的生长均未表现出显著的抑制活性。在小鼠L1210白血病模型中，叶酸的氮杂同系物4和天冬氨酸类似物14与对照动物相比，并未使生存期延长。这些化合物在体内比相应的甲氨蝶呤类似物毒性更大。化合物4支持粪肠球菌（ATCC 8043）的生长，其四氢衍生物支持酿酒片球菌（ATCC 8081）的生长。这些结果有力地表明，4可以替代叶酸衍生物作为丝氨酸转羟甲基酶、胸苷酸合成酶和二氢叶酸还原酶的辅因子。
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