Chamorro C, De Clercq E, Balzarini J, Camarasa M J, San-Félix A
Instituto de Química Médica (C.S.I.C.), Madrid, Spain.
Antivir Chem Chemother. 2000 Jan;11(1):61-9. doi: 10.1177/095632020001100106.
Novel analogues of the anti-HIV-1 lead compound [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]thymine]- 3'-spiro-5'-(4"-amino-1",2"-oxathiole-2',2'-dioxide) (TSAO-T) bearing different amino acids at position N-3 of thymine were prepared and evaluated as inhibitors of HIV replication. The synthesis of the target compounds was accomplished by coupling of the appropriate TSAO intermediate with a conveniently protected (L) amino acid in the presence of BOP and triethylamine, followed by deprotection of the amino acid moiety. Several TSAO derivatives, bearing at N-3 position of the thymine base an L-amino acid retaining the free carboxylic acid, acquired activity against HIV-2, in addition to their inhibitory effect on HIV-1.
制备了抗HIV-1先导化合物[1-[2',5'-双-O-(叔丁基二甲基甲硅烷基)-β-D-呋喃核糖基]胸腺嘧啶]-3'-螺-5'-(4"-氨基-1",2"-氧硫杂环戊烷-2',2'-二氧化物)(TSAO-T)的新型类似物，这些类似物在胸腺嘧啶的N-3位带有不同的氨基酸，并作为HIV复制抑制剂进行了评估。目标化合物的合成是通过在BOP和三乙胺存在下，将适当的TSAO中间体与方便保护的(L)氨基酸偶联，然后对氨基酸部分进行脱保护来完成的。几种在胸腺嘧啶碱基的N-3位带有保留游离羧酸的L-氨基酸的TSAO衍生物，除了对HIV-1有抑制作用外，还获得了抗HIV-2的活性。
