Base-Modified Nucleosides Related to 2-Chloro-2′-deoxyadenosine

Derivatives of 2-chloro-2′-deoxyadenosine ( 1a ) containing secondary 6-NH₂ groups ( 5a-c ) or a 8-Br substituent ( 9 ) were synthesized. They were tested together with ring-modified congeners containing a pyrrolo2,3-b]pyridine, pyrrolo3,2-c]pyridine, or pyrazolo3,4-d]pyrimidine ring system as inhibitors of various leukemic cell lines. Only the 8-Br derivatives 9 showed inhibitory activity, whereas the base-modified congeners were not active. Compound 1a was protonated at a pK_a = 1.4 (2′-deoxyadenosine at pK_a = 3.8). Protonation occurred at N(7) and not at N(1) as observed for dA.