Synthesis and antiviral activity of 9-alkoxypurines. 2. 9-(2,3-Dihydroxypropoxy)-, 9-(3,4-dihydroxybutoxy)-, and 9-(1,4-dihydroxybut-2-oxy)purines
作者:Stuart Bailey、Michael R. Harnden、Richard L. Jarvest、Ann Parkin、Malcolm R. Boyd
DOI:10.1021/jm00105a010
日期:1991.1
(6,7,21a,b, 38a,b,c) by heating with diethoxymethyl acetate afforded 9-alkenoxy- and 9-alkoxy-6-chloropurines (9,10,22a,b, 39a-c, 40a). These were subsequently converted to 9-(2,3-dihydroxypropoxy), 9-(3,4-dihydroxybutoxy), and 9-(1,4-dihydroxybut-2-oxy) derivatives of guanine and 2-aminopurine (13-16, 25-28, 41a-c, 42a). A 2-amino-6-methoxypurine derivative (17) was also prepared. The racemic guanine
烷氧基胺(3,5)或(R,S)-,(R)-和(S)-羟基保护的羟基烷氧基胺(20a,b,37a-c)衍生物与4,6-二氯-2的反应, 5-二甲酰胺基嘧啶(4)并将生成的6-[((烷氧基)氨基]-]和6-(烷氧基氨基)嘧啶(6,7,21a,b,38a,b,c)与二乙氧基乙酸甲酯加热环化,得到9-烯氧基-和9-烷氧基-6-氯嘌呤(9,10,22a,b,39a-c,40a)。随后将它们转化为鸟嘌呤和2-氨基嘌呤的9-(2,3-二羟基丙氧基),9-(3,4-二羟基丁氧基)和9-(1,4-二羟基丁-2-氧基)衍生物(13-16 ,25-28,41a-c,42a)。还制备了2-氨基-6-甲氧基嘌呤衍生物(17)。外消旋鸟嘌呤衍生物13对1型和2型单纯疱疹病毒(HSV-1和HSV-2)具有有效的选择性活性,但对水痘带状疱疹病毒(VZV)的活性较弱。它的抗病毒活性归因于S异构体(28),S异构体的抗HSV