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

Derivatives of 2‐chloro‐2′‐deoxyadenosine ( 1a ) containing secondary 6‐NH 2 groups ( 5a‐c ) or a 8‐Br substituent ( 9 ) were synthesized. They were tested together with ring‐modified congeners containing a pyrrolo[2,3‐ b ]pyridine, pyrrolo[3,2‐ c ]pyridine, or pyrazolo[3,4‐ 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 p K a = 1.4 (2′‐deoxyadenosine at p K a = 3.8). Protonation occurred at N(7) and not at N(1) as observed for dA.