Affiliation: | a School of Pharmacy, Tokyo University of Pharmacy & Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan b Faculty of Pharmaceutical Science, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan |
Abstract: | 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. |