Synthesis and evaluation of novel amidate prodrugs of PMEA and PMPA

  • Bioorg Med Chem Lett. 2001 Apr 23;11(8):1053-6. doi: 10.1016/s0960-894x(01)00128-7.
C Ballatore  1 ,  C McGuigan ,  E De Clercq ,  J Balzarini
Affiliations
  • 1. Welsh School of Pharmacy, Cardiff University, UK.
PMID: 11327587 DOI: 10.1016/s0960-894x(01)00128-7
Abstract

Some novel amidate prodrugs of PMEA and PMPA have been synthesised and tested in vitro for their biological activity. Compound 5 in particular showed greatly enhanced Antiviral potency compared with the parent nucleotide analogue. In vitro enzymatic studies and structure-activity relationships indicate that the degradation mechanism of such prodrugs may be the same as that described for the phosphoramidate triesters of nucleotide analogues.