Lin S C, Holmes G P, Dunn D L, Skinner C G
J Med Chem. 1979 Jun;22(6):741-3. doi: 10.1021/jm00192a024.
A series of 6-substituted and 6,7-disubstituted pyrimido[4,5-b][1,4]oxazines (8-oxadihydropteridines) was synthesized through the condensation of an alpha-halo ketone and 2,5-diamino-4,6-pyrimidinediol. The resulting 8-oxadihydropteridines were assayed as potential antifolates in a dihydrofolate reductase enzyme system. The 2-amino-4-hydroxyoxa-dihydropteridines were found to possess greater biological activity than the corresponding 2,4-diamino compounds. The pteroic acid homeostere 2-amino-4-hydroxy-6-phenethyl-8-oxadihydropteridine was the most potent of the compounds tested.
通过α-卤代酮与2,5-二氨基-4,6-嘧啶二醇的缩合反应，合成了一系列6-取代和6,7-二取代的嘧啶并[4,5-b][1,4]恶嗪（8-氧代二氢蝶啶）。在二氢叶酸还原酶系统中，对所得的8-氧代二氢蝶啶作为潜在的抗叶酸剂进行了测定。发现2-氨基-4-羟基氧代二氢蝶啶比相应的2,4-二氨基化合物具有更高的生物活性。在测试的化合物中，蝶酸同型物2-氨基-4-羟基-6-苯乙基-8-氧代二氢蝶啶活性最强。
