Vince R, Turakhia R H, Shannon W M, Arnett G
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis 55455.
J Med Chem. 1987 Nov;30(11):2026-30. doi: 10.1021/jm00394a017.
(+/-)-(1 alpha,2 beta,3 alpha,5 alpha)-3-[(2,5-Diamino-6-chloro-4- pyrimidinyl)amino]-5-(hydroxymethyl)-1,2-cyclopentanediol (7) was synthesized from 2-amino-4,6-dichloropyrimidine and the carbocyclic xylofuranosylamine (+/-)-(1 alpha,2 beta,3 alpha,5 alpha)-3-amino-5-(hydroxymethyl)-1,2-cyclopentanediol (2) by subsequent preparation of the 5-[(4-chlorophenyl)azo] derivative of the resulting pyrimidine and reduction of the azo moiety with zinc and acetic acid. The carbocyclic analogue of 2-amino-4-chloropurine xylofuranoside (8) and the corresponding 8-azapurine 11 were prepared from 7. The carbocyclic analogues xylofuranosylguanine (9), xylofuranosyl-2,6-diaminopurine (10), xylofuranosyl-8-azaguanine (13), and xylofuranosyl-8-aza-2,6-diaminopurine (14) were prepared from 8 and 11. Compounds 9 and 13 were active against herpes simplex virus (types 1 and 2), with 9 being the more potent against both viruses. Analogue 9 also exhibited potent activity against human cytomegalovirus and varicella-zoster virus.
(±)-(1α,2β,3α,5α)-3-[(2,5-二氨基-6-氯-4-嘧啶基)氨基]-5-(羟甲基)-1,2-环戊二醇(7)由2-氨基-4,6-二氯嘧啶与碳环木糖呋喃胺(±)-(1α,2β,3α,5α)-3-氨基-5-(羟甲基)-1,2-环戊二醇(2)合成，方法是先制备所得嘧啶的5-[(4-氯苯基)偶氮]衍生物，然后用锌和乙酸还原偶氮部分。2-氨基-4-氯嘌呤木糖呋喃糖苷(8)的碳环类似物和相应的8-氮杂嘌呤11由7制备。碳环类似物木糖呋喃基鸟嘌呤(9)、木糖呋喃基-2,6-二氨基嘌呤(10)、木糖呋喃基-8-氮杂鸟嘌呤(13)和木糖呋喃基-8-氮杂-2,6-二氨基嘌呤(14)由8和11制备。化合物9和13对单纯疱疹病毒(1型和2型)有活性，其中9对两种病毒的活性更强。类似物9对人巨细胞病毒和水痘带状疱疹病毒也表现出强效活性。
