| |
[摘要]：Microscopic equil. dissocn. consts., kas, were detd. for four nitrogen-contg. bisphosphonates (N-BP): risedronate and its analogs 2-(2-aminophenyl)-1-hydroxyethylidene-1,1-bisphosphonate, NE 11807, and NE 97220. The proportion of each and of analogs 2-(3'-(N-ethyl)pyridinium)-ethylidenebisphosphonate and 2-(3-piperinidyl)-1-hydroxyethylidene-1,1-bisphosphonate, having a pos. charged nitrogen and three neg. charges on the bisphosphonate group ("carbocation analog") at pH 7.5, was calcd. When set in order of increasing potency at inhibiting farnesyl diphosphate (FDP) synthase (their intracellular target), the N-BPs are also ranked in order of decreasing mole fraction of carbocation analog. However, only a weak correlation exists between potency for inhibiting FDP synthase and potency for inhibiting Dictyostelium discoideum growth. It is concluded that, although high potency for inhibiting FDP synthase is favored when the nitrogen atom in a N-BP is uncharged, N-BPs having a pos. charged nitrogen can still be potent inhibitors of Dictyostelium growth owing to favorable interaction with a second, unidentified target. |
|
