Replacement of 3'-CH group by nitrogen in the carbocyclic analog of thymidine

Abstract
We have prepared (4R)-4-thyminyl-D-prolinol, an analogue of 3''-deoxythymidine in which the sugar has been replaced by D-prolinol. This strongly basic secondary amine has been converted to the corresponding hydroxylamine, an analogue of either thymidine or 2''-deoxyxylofuranosylthymine. We have also synthesized a number of simple derivatives of the amine for testing in vitro activity against herpes simplex 1 (HSV-1), human immunodeficiency virus 1 (HIV-1), and a panel of human tumor cell lines. Among these compounds, the hydroxylamine 12 proved active against the human tumor cell lines of breast, colon, and lung origin, with IC50 values of 0.08, 14.02, and 6.91 .mu.M, respectively.