Stable and water soluble amino acid phosphomonoester amidates of AZT were synthesized and shown to have potent anti-HIV-1 activity. Intracellular and cell extract metabolism studies revealed that these compounds are likely to be enzymatically converted to the corresponding monophosphates. In addition, we have shown that the half life and tissue distribution of a phosphoramidate of AZT is 5 and 10-fold greater, respectively, than AZT.
Bibliographical noteFunding Information:
We wish to thank Dr. R.F.Schinazi, Dr. W. G. Rice, Dr. Y. Pommier and Dr. J.-L. Imbach for their help and suggestions throughout this study. This study was partially supported by grants CA61908 (C.R.W.) from the National Institutes of Health. E.J.M. was supported by the National Institute of Health Pharmacological Sciences Training grant GM07994.