Claims
- 1. A compound of the formula: wherein:R31 is a linear or branched polymer residue; Y10 and Y11 are independently O, S, or NR40; X2 is O, S or NR41; R32, R33, R34, R35, R37, R38, R39, R40, R41, R50 and R51 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls and substituted C1-6 heteroalkyls, a, b and e are each independently a positive integer. L is an amino acid residue or a bifunctional linker; wherein Y12 and Y13 are independently O, S,or NR41; Z is selected from the group consisting of a bond, a moiety that is actively transported into a target cell, a hydrophobic moiety, and combinations thereof; D1 and D2 are independently selected from the group consisting of OH, a residue of a hydroxyl-containing moiety, a residue of an amine-containing moiety and a leaving group; and Y1 and Y2 are independently selected positive integers.
- 2. The compound of claim 1, wherein R1 is O—(CH2CH2O)x or O—(CH(CH3)CH2O)x, wherein x is from about 10 to about 2,300.
- 3. The compound of claim 1 wherein L is selected from the group consisting of: whereinX5 is O, S, or N R43; Y15 is O, S, or NR44; R43, R44 and R54-R58 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls and substituted C1-6 heteroalkyls; and g is a positive integer.
- 4. The compound of claim 1 wherein D1 and D2 are residue of an active biological agent, an anticancer prodrug, a detectable tag, and combinations thereof.
- 5. A method of preparing a polymeric conjugate, comprising reacting a compound of formula (XII) whereinR31 is a linear or branched polymer residue; Y10 and Y11 are independently O, S, or NR40; L is an amino acid residue or a bifunctional linker; R32, R33, R34, R35, R37, R38, and R40 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls and substituted C1-6 heteroalkyls; a and b are each independently a positive integer, and B is a leaving group; with a compound of the formula (XIII) whereinX2 is O, S, or NR41; R39, R41, R50 and R51 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls and substituted C1-6 heteroalkyls; wherein Y12 and Y13 are independently O, S, or NR41; Z is selected from the group consisting of a bond, a moiety that is actively transported into a target cell, a hydrophobic moiety, and combinations thereof; D1 and D2 are independently selected from the group consisting of OH, a residue of a hydroxyl, a residue of an amine-containing moiety and a leaving group; e is a positive integer; and y1 and y2 are independently selected positive integers; under conditions sufficient to cause a substitution reaction in which the compound of formula (X) is formed, and isolating the polymer conjugate of formula (X).
- 6. A method of treating mammals with polymeric conjugates, comprising administering an effective amount of the compound of claim 1.
- 7. The compound of claim 3 wherein g is 1 or 2.
- 8. The compound of claim 2, wherein R31 is a polymer having a weight average molecular weight ranging from about 2,000 to about 100,000.
- 9. The compound of claim 2, wherein R31 is a polymer having a weight average molecular weight of from about 5,000 to about 50,000.
- 10. The compound of claim 2, wherein R31 is a polymer having a weight average molecular weight of from about 20,000 to about 40,000.
- 11. The compound of claim 1, having the formula:
- 12. The compound of claim 1, wherein Y11 and Y12 are both.
- 13. The compound of claim 1, wherein R32-R35, R37-R40, R50, and R51 are each hydrogen.
- 14. The compound of claim 1, wherein a and b are each 1.
- 15. The compound of claim 1, wherein y1 and y2 are both or 1.
CROSS-REFERENCE TO RELATED APPLICATION
This application is a continuation-in-part of U.S. patent application Ser. No. 09/293,557 filed Apr. 15, 1999, now U.S. Pat. No. 6,251,382 which claims the benefit of priority from U.S. Patent Provisional Application Serial No. 60/082,105 filed Apr. 17, 1998, the contents of each of which are incorporated herein by reference.
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Oct 1999 |
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Provisional Applications (1)
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Number |
Date |
Country |
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60/082105 |
Apr 1998 |
US |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
09/293557 |
Apr 1999 |
US |
Child |
09/888072 |
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US |