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  • Title: Pyridinium-1-yl bisphosphonates are potent inhibitors of farnesyl diphosphate synthase and bone resorption.
    Author: Sanders JM, Song Y, Chan JM, Zhang Y, Jennings S, Kosztowski T, Odeh S, Flessner R, Schwerdtfeger C, Kotsikorou E, Meints GA, Gómez AO, González-Pacanowska D, Raker AM, Wang H, van Beek ER, Papapoulos SE, Morita CT, Oldfield E.
    Journal: J Med Chem; 2005 Apr 21; 48(8):2957-63. PubMed ID: 15828834.
    Abstract:
    We report the design, synthesis and testing of a series of novel bisphosphonates, pyridinium-1-yl-hydroxy-bisphosphonates, based on the results of comparative molecular similarity indices analysis and pharmacophore modeling studies of farnesyl diphosphate synthase (FPPS) inhibition, human Vgamma2Vdelta2 T cell activation and bone resorption inhibition. The most potent molecules have high activity against an expressed FPPS from Leishmania major, in Dictyostelium discoideum growth inhibition, in gammadelta T cell activation and in an in vitro bone resorption assay. As such, they represent useful new leads for the discovery of new bone resorption, antiinfective and anticancer drugs.
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