Bisphosphonate conjugates and methods of making and using the same
AssigneeMBC Research, Inc.
InventorsNelly Padioukova, Sergey Mikhailov, H.B.F. Dixon, Grigorii Tzeitline
Life of this patent
Estimating the term…
Abstract
The present invention is directed to particular bisphosphonate compounds, and in particular, to bisphosphonate conjugates that are useful in the treatment of soft tissues surrounding bone and bone-related diseases, such as bone cancer and osteoporosis.
Claims24
A composition useful in treating or preventing bone infection or bone cancer, comprising:
- (a) an effective amount of bisphosphonate conjugate having the structure:
- 7
- where:
- X=O, S or N;
- Y=residue of anti-cancer or antibiotic compound.
- R1=H;
- R2=R3, OR3, NR3, SR3
- R3=H, alkyl, aryl, cycloalkyl, heteroaryl, NH2.
- (b) and a pharmaceutically-acceptable excipient.
A composition useful in treating or preventing bone infection or bone cancer, comprising:
- (a) an effective amount of bisphosphonate conjugate having the structure:
- 8
- where:
- X=O, S or N;
- Z=O, S, N
- Y=residue of anti-cancer or antibiotic compound;
- R1=H;
- R2=R3, OR3, NR3, SR3;
- R3=H, alkyl, aryl, cycloalkyl, heteroaryl, NH2;
- and
- (b) a pharmaceutically-acceptable excipient.
A bisphosphonate conjugate capable of releasing an anticancer or antibiotic component upon binding to bone tissue, having the structure:
- 9
- where:
- X=O, S or N;
- Y=residue of anti-cancer or antibiotic compound;
- R1=H;
- R2=R3, OR3, NR3, SR3;
- and
- R3=H, alkyl, aryl, cycloalkyl, heteroaryl, NH2.
A bisphosphonate conjugate capable of releasing an anticancer or antibiotic component upon binding to bone tissue, having the structure:
- 10
- where:
- X=O, S or N;
- Z=O, S, N
- Y=residue of anti-cancer or antibiotic compound;
- R1=H;
- R2=R3, OR3, NR3, SR3, and R3=H, alkyl, aryl, cycloalkyl, heteroaryl, NH2.
A bisphosphonate conjugate useful in treating or preventing disorders of abnormal calcium and phosphate metabolism, comprising, a pharmaceutically-acceptable salt or esters thereof, characterized in that they have the general structure:
- O═P(OH)2—C(R1,R2)—P(O)(OH)—X—Y
- where X=O,S,N atom, Y=residue of organic compound
- and where
- R1=H,alkyl, aryl, cycloalkyl, heteroyl, NH2;
- R2=OR3,NR3,R3,SR3;
- and
- R3=H,alkyl, aryl, cycloalkyl, heteroyl, NH2.
A bisphosphonate conjugate capable of releasing an antibiotic or cytotoxic component upon binding with bone tissue, such conjugates useful in treating or preventing bone infection or bone cancer, comprising a pharmaceutically-acceptable salt and esters thereof, characterized in that they have the general structure:
- O═P(OH)2—C(R1,R2)—P(O)(OH)—X—Y
- where X=O, S, N atom, Y=a residue of a cytotoxic compound;
- and where
- R1=H,alkyl, aryl, cycloalkyl, heteroyl, NH2;
- R2=H,OR3,NR3,R3,SR3;
- and
- R3=H, alkyl, aryl, cycloalkyl, heteroyl, NH2.
A vitamin-containing bisphosphonate conjugate useful in treating and preventing disorders of abnormal calcium and phosphate metabolism, comprising a pharmaceutically-acceptable salt, and esters thereof, having the structure:
- [O═P(OH)2]2—C(R1,R2);
- where
- R1=OH,H;
- R2=(CH2)n—X;
- n=1-10;
- X=a vitamin residue or its phosphorylated derivative;
- and
- R1=Y-X;
- [O═P(OH2]2—C(R11R2) where
- Y=N,O,S atom;
- X=vitamin residue or its phosphorylated derivative;
- and
- R2=H,alkyl,aryl,heteroyl and their functional derivatives.
Dependencies are inferred from the claim text.