Application of phosphoramidate ProTide technology significantly improves antiviral potency of carbocyclic adenosine derivatives

C McGuigan, A Hassan-Abdallah…

Index: McGuigan, Christopher; Hassan-Abdallah, Alshaimaa; Srinivasan, Sheila; Wang, Yikang; Siddiqui, Adam; Daluge, Susan M.; Gudmundsson, Kristjan S.; Zhou, Huiqiang; McLean, Ed W.; Peckham, Jennifer P.; Burnette, Thimysta C.; Marr, Harry; Hazen, Richard; Condreay, Lynn D.; Johnson, Lance; Balzarini, Jan Journal of Medicinal Chemistry, 2006 , vol. 49, # 24 p. 7215 - 7226

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Citation Number: 33

Abstract

We report the application of phosphoramidate pronucleotide (ProTide) technology to the antiviral agent carbocyclic l-d4A (l-Cd4A). The phenyl methyl alaninyl parent ProTide of l- Cd4A was prepared by Grignard-mediated phosphorochloridate reaction and resulted in a compound with significantly improved anti-HIV (2600-fold) and HBV activity. We describe modifications of the aryl, ester, and amino acid regions of the ProTide and how these ...