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.