Abstract The synthesis of 2′-deoxy and 2′,3′-dideoxy derivatives of 1-s-D-ribofuranosyl-1,3,4,7-tetrahydro-2H-1,3-diazepin-2-one (2) was undertaken in order to find new cytidine deaminase (CDA) inhibitors and potential adjuvants in anticancer chemotherapy. Replacement of ribose by a 2-deoxyribose moiety led to compound 9 that appeared slightly more potent than 2 (Ki = 2.5 × 10−8 M). Remarkably, the corresponding α-2′-deoxynucleoside 10 acted as a very potent inhibitor of human placenta CDA, with a Ki = 7.5 × 10−8 M. Attempt to synthesize the 2′,3′-dideoxy derivative of 2 led to N-[4,5-dihydroxy-1-(2-oxo-2,3,4,7-tetrahydro[1,3] diazepin-1-yl)-pentyl]-2,2,2-trifluoroacetamide (13), which is devoid of CDA inhibitory activity.