Synthesis of 1,1-difluoro-5-(1H-9-purinyl)-2-pentenylphosphonic acids and the related methano analogues. Remarkable effect of the nucleobases and the cyclopropane rings on inhibitory activity toward purine nucleoside phosphorylase Original Research Articl

A series of 1,1-difluoro-5-(1H-9-purinyl)-2-pentenylphosphonic acids, (E)-2a,b and (Z)-2a,b, as well as the related methano analogues (±)-3a,b and (±)-4a,b were prepared for evaluation of their PNP inhibitory activities. The cyclopopane ring and the hypoxanthine residue were found to increase the profile of inhibitory activity. The IC50 and Ki values of difluoro{(1R∗,2S∗)-2-[2-(6-oxo-6,9-dihydro-1H9-purinyl)ethyl]cyclopropyl}methylphosphonic acid (±)-3b toward PNP purified from Cellulomonas sp. were determined to be 70 nM and 8.8nM, respectively.