Presentation of the β -Carboxamidophosphonate Arrangement in Substrate Structures Targeting HIV-1 PR

Novel O, O-diethyl 1-benzamido- 2,2-biscarbamoylethanephosphonates were synthesised as putative substrates to HIV-1 PR, to exploit the state of activation of the phosphonate electrophilic function in beta-carboxamidophosphonate arrangements. O, O-Diethyl 1-benzamido- 2,2- bis[(1S)-N-(1-benzyl-2-hydroxyethyl) carbamoyl]ethanephosphonate exhibited moderate anti-HIV activity in vitro (EC(50) = 53 mu M) while its depsipeptide analogue; O, O-diethyl 1-benzamido- 2,2bis[(1S)-N-(1-benzyl-2-{(2'S)-leucinyloxy} ethyl) carbamoyl] ethanephosphonate inhibited HIV-1 PR (IC(50) = 31 mu M).