Rosowsky A, Forsch R
J Med Chem. 1982 Dec;25(12):1454-9. doi: 10.1021/jm00354a013.
N-[[[(2,4-Diaminopteridin-6-yl)methyl]amino]benzyl]-L-glutamic acid ("deoxoaminopterin", 1), a new aminopterin analogue containing a CH2 group in the side chain in place of the amide C = O, was synthesized by condensation of 2,4-diamino-6-(bromomethyl)pteridine with diethyl N-(p-aminobenzyl)-L-glutamate, followed by saponification with a stoichiometric amount of barium hydroxide in 50% ethanol. The apparent importance of the amide C = O group as a structural determinant of biological activity was indicated by the finding that 1 has 10- to 20-fold lower affinity for bacterial and mammalian dihydrofolate reductase than aminopterin, is not toxic to L1210 murine leukemia cells in culture at a concentration of up to 1.0 microM, and shows no antitumor effect in L1210 leukemic mice at doses as high as 240 mg/kg (q3d X 3).
N-[[[(2,4-二氨基蝶啶-6-基)甲基]氨基]苄基]-L-谷氨酸（“脱氧氨基蝶呤”，1）是一种新的氨基蝶呤类似物，其侧链中的酰胺羰基被亚甲基取代，通过2,4-二氨基-6-(溴甲基)蝶啶与N-(对氨基苄基)-L-谷氨酸二乙酯缩合，然后在50%乙醇中用化学计量的氢氧化钡皂化合成。酰胺羰基作为生物活性结构决定因素的明显重要性体现在以下发现中：1对细菌和哺乳动物二氢叶酸还原酶的亲和力比对氨基蝶呤低10至20倍，在浓度高达1.0微摩尔时对培养中的L1210小鼠白血病细胞无毒，并且在剂量高达240毫克/千克（每3天一次，共3次）时对L1210白血病小鼠没有抗肿瘤作用。
