Programmable polymeric drugs

1. A compound having the following structure (I):

or a stereoisomer, pharmaceutically acceptable salt or tautomer thereof, wherein:

M at each occurrence, independently has one of the following structures:

provided that at least one occurrence of M does not have the following structure:

L is, at each occurrence, independently a nitrogen containing linker;

L 1 , L 2 and L 3 are, at each occurrence, independently an optional alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene, heteroalkynylene or heteroatomic linker;

R 1 is, at each occurrence, independently H, alkyl or alkoxy;

R 2 and R 3 are each independently H, OH, SH, alkyl, alkoxy, alkylether, heteroalkyl, —OP(═R a )(R b )R c , Q, or L′;

R a is O or S;

R b is OH, SH, O − , S − , OR d or SR d ;

R c is OH, SH, O − , S − , OR d , OL′, SR d , alkyl, alkoxy, heteroalkyl, heteroalkoxy, alkylether, alkoxyalkylether, phosphate, thiophosphate, phosphoalkyl, thiophosphoalkyl, phosphoalkylether or thiophosphoalkylether;

R d is a counter ion;

Q has one of the following structures:

wherein x is halo;

L′ is, at each occurrence, independently a linker comprising a covalent bond to Q, an antibody or a cell surface receptor antagonist, a linker comprising a covalent bond to an antibody or a cell surface receptor antagonist, a linker comprising a covalent bond to a solid support, or a linker comprising a covalent bond to a solid support residue; and

n is an integer of one or greater.

2. The compound of claim 1 , wherein L 1 is a heteroalkylene linker.

3. The compound of claim 1 , wherein the compound has the following structure (IA):

wherein:

L 4 is, at each occurrence, independently an alkylene, alkenylene, alkynylene, heteroalkylene, heteroalkenylene or heteroalkynylene linker;

R 4 is, at each occurrence, independently OH, SH, O − , S − , OR d or SR d ;

R 5 is, at each occurrence, independently oxo, thioxo or absent; and

m is, at each occurrence, independently an integer of zero or greater.

4. The compound of claim 3 , wherein L 4 is at each occurrence, independently a heteroalkylene linker.

5. The compound of claim 4 , wherein L 4 is at each occurrence, independently an alkylene oxide linker.

6. The compound of claim 3 , wherein L 2 and L 3 are, at each occurrence, independently C 1 -C 6 alkylene, C 2 -C 6 alkenylene or C 2 -C 6 alkynylene.

7. The compound of claim 3 , wherein L 4 is, at each occurrence, independently C 1 -C 6 alkylene or C 2 -C 6 alkynylene.

8. The compound of claim 3 , wherein the compound has the following structure (ID):

wherein:

x 1 , x 2 , x 3 and x 4 are, at each occurrence, independently an integer from 0 to 6; and

y is an integer from 1 to 6.

9. The compound of claim 8 , wherein at least one occurrence of x 1 , x 2 , x 3 or x 4 is 1.

10. The compound of claim 8 , wherein x 1 , x 2 , x 3 and x 4 are each 1 at each occurrence.

11. The compound of claim 3 , wherein R 4 is, at each occurrence, independently OH, O − or OR d .

12. The compound of claim 3 , wherein R 5 is, at each occurrence, oxo.

13. The compound of claim 1 , wherein R 1 is, at each occurrence, H.

14. The compound of claim 1 , wherein R 2 and R 3 are each independently OH or —OP(═R a )(R b )R c .

15. The compound of claim 1 , wherein one of R 2 and R 3 is OH or —OP(═R a )(R b )R c , and the other of R 2 and R 3 is Q or a linker comprising a covalent bond to Q.

16. The compound of claim 1 , wherein one of R 2 and R 3 is —OP(═R a )(R b )R c or L′.

17. The compound of claim 16 , wherein R c is OL′.

18. The compound of claim 16 , wherein L′ is an antibody or a cell surface receptor antagonist or a linker to an antibody or a cell surface receptor antagonist.

19. The compound of claim 18 , wherein L′ is a linker to an antibody or a cell surface receptor antagonist, the linker comprising an alkylene oxide or phosphodiester moiety, or combinations thereof.

20. The compound of claim 19 , wherein L′ has the following structure:

wherein:

m″ and n″ are independently an integer from 1 to 10;

R e is H, an electron pair or a counter ion;

L″ is the antibody or cell surface receptor antagonist or a linkage to the antibody or cell surface receptor antagonist.

21. The compound of claim 1 , wherein the antibody or cell surface receptor antagonist is an epidermal growth factor receptor (EGFR) inhibitor, a hepatocyte growth factor receptor (HGFR) inhibitor, an insulin-like growth factor receptor (IGFR) inhibitor, a folate, or a MET inhibitor.

22. The compound of claim 1 , wherein R 2 or R 3 has one of the following structures:

23. The compound of claim 1 , wherein R 2 or R 3 has the following structure:

24. The compound of claim 3 , wherein m is, at each occurrence, independently an integer from 1 to 5.

25. The compound of claim 1 , wherein n is an integer from 1 to 10.

26. The compound of claim 1 , wherein M is, at each occurrence, independently an anti-cancer drug, and the antibody or cell surface receptor antagonist is an antibody specific for a tumor cell antigen.

27. The compound of claim 26 , wherein the tumor cell antigen is an EGFR, a HER 2, a folate receptor, CD20, or CD33.

28. A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

29. A method of treating a disease, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 , wherein each M is independently a biologically active moiety effective for treating the disease.

30. The method of claim 29 , wherein the disease is cancer, and each M is an anti-cancer drug.

31. The method of claim 30 , wherein each occurrence of M has the following structure:

32. The method of claim 29 , wherein at least one occurrence of M has one of the following structures:

33. The method of claim 29 , wherein each occurrence of M has one of the following structures:

34. The compound of claim 1 , wherein the nitrogen containing linker L is, at each occurrence, independently —NH—, —NH(CH 2 ) 4 —, or —NH(CH 2 ) 3 OCH 2 —.