Design and synthesis of the 3′‐aminocarbonylamino, aminothiocarbonylamino and N ‐(Hydroxy)guanidinyl derivatives of thymidine as potential anti‐HIV agents

The 3′‐substituted‐3′‐deoxythymidines 3a (urea), 3b (thiourea) and 3c [ N ‐(hydroxy)guanidinyl)] were designed based on the known structure‐activity correlations for the active anti‐HIV agent, 3′‐azido‐3′‐deoxythymidine (AZT). Hydrolysis of 3′‐cyanamido‐3′‐deoxythymidine ( 2 ) with ammonium hydroxide in the presence of hydrogen peroxide afforded the 3′‐urea analogue 3a , whereas reaction with hydrogen sulfide in methanol gave the 3′‐thiourea derivative 3b. The 3′‐[ N ‐(hydroxy)guanidinyl] compound 3c was synthesized by reaction of the 3′‐cyanamide 2 with hydroxylamine.