Synthesis and antiretroviral evaluation of derivatives of zidovudine

a series of zidovudine (azt, 1) derivatives have been synthesized and their anti-hiv activity and cytotoxicity have been determined. the 5'-oh function of azt was derivatized using n, n'-carbonyldiimidazole and different amine compounds leading to their 5'-o-carbamates. in addition, two known azt derivatives 5'-o-tosylate and a tricyclic one (azt-cycl) were also obtained by a simpler procedure than those previously reported. although these azt derivatives were less toxic than azt, their reduced cytotoxicity was concomitant with an inability to inhibit hiv-1 replication, except in the case of azt-cycl, which showed an ic50 = 1 μmol l-1 without cytotoxicity with values of ccid50 ( μmol l-1) > 1000.