Twenty-six 5-azacytidine analogues have been synthesized, including 4-amino- 6-alkyl-1-pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H)-ones 1a-j, 6-amino-4-alkyl/aryl-1- pyranosyl/ribofuranosyl-1,3,5-triazin-2(1H)-ones 2a-f and 4-amino-6-alkyl-1,3,5-triazin-2- yl-1-thio-pyranosides/ribofuranosides 3a-j. The antiproliferative activities of these synthetic analogues were investigated in human leukemia HL-60 cells. Ribofuranosyl S-nucleoside 3a, a bioisostere of 5-azacytidine, had a similar antiproliferative ability as that of the latter. Introduction of a methyl at the 6 position of 5-azacytidine and/or replacement of the ribofuranosyl moiety with pyranosyl sugars or disaccharides significantly decreased the antiproliferative activities of the 5-azacytidine derivatives. Several compounds with the replacement of pyranosyl sugars enhanced all-trans retinoic acid-induced differentiation ability in human leukemia HL-60 cells.