BASE-MODIFIED NUCLEOSIDES RELATED TO 2-CHLORO-2'-DEOXYADENOSINE

Abstract

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 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 la 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.