8-Amino-3-deazaguanine (15), an analogue of both 3-deazaguanine (1) and 8-aminoguanine (6), an antitumor agent and a purine nucleoside phosphorylase (PNP) inhibitor, respectively, was synthesized from the ammonolysis of an imidazole precursor, methyl 2-(benzoylamino)-5-(cyanomethyl)-1H-imidazole-4-carboxylate (13). The requisite imidazole, methyl 2-(benzoylamino)-4-(methoxycarbonyl)-1H-imidazole-5-acetate (11), was prepared from the monoheterocyclic rearrangement of dimethyl 3-[(5-phenyl-1,2,4-oxadiazol-3-yl)amino]-2-pentenedioate (10) by NaH/DMF. Ammonolysis and subsequent dehydration of 11 provided the penultimate imidazole intermediate 13. Its deprotected (NaOMe/100 degrees C) product, methyl 2-amino-5-(cyanomethyl)-1H-imidazole-4-carboxylate (14), was also converted to 15. 8-Amino-3-deazaguanine, as its methanesulfonic acid (mesylate 7), exhibited an inhibition constant (IC50) of 9.9 microM against isolated mammalian PNP. It was a very weak inhibitor of T and B cell growth and did not enhance 2'-deoxyguanosine toxicity in the same cells. 8-Amino-3-deazaguanine mesylate was not significantly active in L1210 cells in vitro or L1210 leukemic mice. Thus, the amino group introduced in the 8-position of 3-deazaguanine enhances its PNP activity but diminishes its antitumor activity.

中文翻译：

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通过咪唑前体合成8-氨基-3-脱氮鸟嘌呤。嘌呤核苷磷酸化酶的抗肿瘤活性和抑制作用。

分别从3-脱氮鸟嘌呤（1）和8-氨基鸟嘌呤（6）的类似物8-氨基-3-脱氮鸟嘌呤（15），抗肿瘤药和嘌呤核苷磷酸化酶（PNP）抑制剂合成。咪唑前体2-（苯甲酰基氨基）-5-（氰甲基）-1H-咪唑-4-羧酸甲酯（13）。必要的咪唑2-（苯甲酰基氨基）-4-（甲氧羰基）-1H-咪唑-5-乙酸甲酯（11）由3-[（5-苯基-1,2,4-）二甲基的单杂环重排制备NaH / DMF制得的恶二唑-3-基）氨基] -2-戊二烯酸酯（10）。氨解和随后的脱水11提供了倒数第二个咪唑中间体13。其脱保护的（NaOMe / 100°C）产物2-氨基-5-（氰基甲基）-1H-咪唑-4-羧酸甲酯（14）也转化为15. 8-氨基-3-脱氮鸟嘌呤，作为其甲磺酸（甲磺酸酯7），对分离的哺乳动物PNP的抑制常数（IC50）为9.9 microM。它是T和B细胞生长的非常弱的抑制剂，在相同细胞中没有增强2'-脱氧鸟苷的毒性。8-氨基-3-脱氮鸟嘌呤甲磺酸盐在体外L1210细胞或L1210白血病小鼠中无明显活性。因此，在3-脱氮鸟嘌呤的8位引入的氨基增强了其PNP活性，但减弱了其抗肿瘤活性。