Systematic Study of the Physicochemical Properties of a Homologous Series of Aminobisphosphonates

Aminobisphosphonates, e. g., alendronate and neridronate, are a well known class of molecules used as drugs for various bone diseases. Although these molecules have been available for decades, a detailed understanding of their most important physicochemical properties under comparable conditions is lacking. In this study, ten aminobisphosphonates, H2N(CH2)(n)C(OH)[P(O)(OH)(2)](2), in which n = 2-5, 7-11 and 15 have been synthesized. Their aqueous solubility as a function of temperature and pH, pK(a)-values, thermal stability, IR absorptions, and NMR spectral data for both liquid (H-1, C-13, P-31-NMR) and solid state (C-13, N-15 and P-31-CPMAS NMR) were determined.