Novel quaternary nitrogen-containing phosphonate compounds, pharmaceutical compositions, and methodsfor treating abnormal calcium and phosphate metabolism.

摘要

Disclosed are quaternary nitrogen-containing, saturated or unsaturated monocyclic and bicyclic ring-containing bisphosphonate compounds, and pharmaceutically-acceptable salts and esters thereof. These compounds, which are useful for treating or preventing disorders of calcium and phosphate metabolism, have the following general structure: cted from nil, O, S, NR1 and N+(R2)2; if no R1 is N+(R2)2, then at least one of X or Y must be N+(R2)2; (b) m and n and m+n are integers from 0 to 5; p and q and p+q are integers from 0 to 3; (c) s is an integer from 0 to 2 and when m+n=0 and X is nil, s=2; (d) each R1 is independently selected from the group consisting of nil, N+(R2)2, R9SR6, SR6, hydrogen, hydroxy; unsubstituted or substituted C1-C8 alkyl, -OR3, -CO2R3, -O2CR3, NR32, -N(R3)C(O)R3, -C(O)N(R3)2, halogen, -C(O)R3, arylalkyl, nitro, unsubstituted or substituted aryl, -OH and combinations thereof; (e) each R2 is independently selected from the group consisting of nil; substituted or unsubstituted C1-C35 alkyl, substituted or unsubstituted phenyl, benzyl, or R9SR6; (f) each R3 is independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-C8 alkyl, and R9SR6; (g) each R6 is independently selected from the group consisting of H, -C(O)R7, C(O)OR7, C(S)OR7, C(S)R7, C(O)NR72, and C(S)NR72, wherein R7 is hydrogen or substituted or unsubstituted C1-C8 alkyl; (h) R is PO3H2 or P(O)(OH)R4, wherein R4 is substituted or unsubstituted C1-C8 alkyl; and (i) R9 is substituted or unsubstituted C1-C8 alkyl.