Claims
- 1. A compound comprising the formula:
- 2. The compound of claim 1, wherein R1 further comprises a capping group A selected from the group consisting of hydrogen, CO2H, C1-6 alkyl moieties, dialkyl acyl urea alkyls and
- 3. The compound of claim 1, wherein Y1 and Y2 are oxygen.
- 4. The compound of claim 1, wherein R2-5, R7 and R8 are hydrogen.
- 5. The compound of claim 1, wherein X is selected from the group consisting of O, S, SO, SO2, C(Y3) and NR6, wherein Y3 is selected from the group consisting of O, S and R9, and R6 is 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.
- 6. The compound of claim 1, wherein Q is selected from the group consisting of C2-4 alkyls, cycloalkyls, aryls, aralkyl groups substituted with a member of the group consisting of NH, O, S, —CH2—C(O)—NH—, and ortho-substituted phenyls.
- 7. The compound of claim 1, wherein (p1) and (p2) are 1.
- 8. The compound of claim 1, wherein (n1) and (n2) are individually 1 or 2.
- 9. The compound of claim 8, wherein (n1) is 1 and (n2) is 2.
- 10. The compound of claim 1, wherein (m1) and (m2) are 1.
- 11. The compound of claim 1, wherein (q) is 1.
- 12. The compound of claim 1, wherein R1 comprises a polyalkylene oxide residue.
- 13. The compound of claim 12, wherein said polyalkylene oxide residue comprises polyethylene glycol.
- 14. The compound of claim 1 wherein said polymeric residue has a molecular weight of from about 2,000 to about 100,000.
- 15. The compound of claim 14, wherein said polymeric residue has a molecular weight of from about 20,000 to about 40,000.
- 16. The compound of claim 1 wherein B is a residue of a member of the group consisting of Ara-C, camptothecin, camptothecin analogs, paclitaxel, taxoteres, gemcitabine, podophyllotoxin, fluconazole, ciclopirox, amphoteracin B, nystatin, doxorubicin, daunorubicin, maytansine, vancomycin and erythromycin.
- 17. The compound of claim 1 wherein B is a residue of a member of the group consisting of anti-tumor agents; cardiovascular agents, anti-neoplastics anti-infectives, anti-fungals, anti-anxiety agents, gastrointestinal agents, central nervous system-activating agents, analgesics, fertility or contraceptive agents, anti-inflammatory agents, steroidal agents, anti-urecemic agents, cardiovascular agents, vasodilating agents and vasoconstricting agents.
- 18. A compound of claim 1, having a formula selected from the group consisting of:
- 19. A compound of claim 1, having a formula selected from the group consisting of:
- 20. A method of preparing a polymeric transport system, comprising
a) reacting a compound of formula: 36E1-4 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, substituted C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxy, phenoxy, C1-6 heteroalkoxy, 37and at least one of E1-4 includes a B moiety, wherein B is a leaving group, OH or 38wherein J1 is the same as J, or another member of the group defining J and E5 is the same as E1-4 or another member of the group defining E1-4; Y1 is O, S, or NR9; R4-5 and R7-9 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, C1-5 heteroalkyls, substituted C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxy, phenoxy, and C1-6 heteroalkoxy; (m1) and (m2) are independently zero or one; (n1), (n2), (p1), and (p2) are independently zero or a positive integer; and (Z) is an electron withdrawing group; with a compound of the formula: 39wherein
B2 is a leaving group which is capable of reacting with an unprotected amine; Y2 is O, S, or NR9;
q is independently zero or a positive integer; R2-3 are 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, substituted C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxy, phenoxy, and C1-6 heteroalkoxy, M is a heteroatom selected from either X or Q; wherein X is an electron withdrawing group and Q is a moiety containing a free electron pair positioned three to six atoms from C(═Y2); and (R1) is a polymeric residue; and b) reacting the resultant compound with a sufficient amount of a biologically active moiety having a substitutable hydroxyl or amino group.
- 21. A method of preparing a polymeric transport systems comprising
a) reacting a sufficient amount of a biologically active moiety having a substitutable hydroxyl or amino group with a compound of the formula: 40wherein B3 is a cleavable protecting group; 41E1-4 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, substituted C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxy, phenoxy, C1-6 heteroalkoxy, 42and at least one of E1-4 includes a B moiety, wherein B is a leaving group, OH, or 43wherein J1 is the same as J, or another member of the group defining J and E5 is the same as E1-4 or another member of the group defining E1-4; Y1 is O, S, or NR9; R4-5 and R7-9 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, substituted C1-6 heteroalkyls; substituted C1-6 heteroalkyls, C1-6 alkoxy, phenoxy, and C1-6 heteroalkoxy; (m1) and (m2) are independently zero or one; (n1), (n2), (p1), and (p2) are independently zero or a positive integer; and (Z) is an electron withdrawing group; with a biologically active moiety having a hydroxyl or amine group; b) deprotecting the resultant intermediate by removing B3; and c) reacting the deprotected intermediate compound with a compound of the formula 44wherein
B2 is a leaving group which is capable of reacting with an unprotected amine; Y2 is O, S, or NR9; q is independently zero or a positive integer; R2-3 are 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, substituted C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxy, phenoxy, and C1-6 heteroalkoxy; M is a heteroatom selected from either X or Q; wherein X is an electron withdrawing group and Q is a moiety containing a free electron pair positioned three to six atoms from C(═Y2); and (R1) is a polymeric residue.
- 22. A method of treating a mammal with prodrugs, comprising:
administering to a mammal in need of such treatment an effective amount of a composition of claim 1 where in B is a residue of a biologically active moiety.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. patent application Ser. No. 09/062,305 filed Apr. 17, 1998, the contents of which are incorporated herein by reference.
Continuations (2)
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10067930 |
Feb 2002 |
US |
Child |
10638031 |
Aug 2003 |
US |
Parent |
09293624 |
Apr 1999 |
US |
Child |
10067930 |
Feb 2002 |
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Continuation in Parts (1)
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Number |
Date |
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Parent |
09062305 |
Apr 1998 |
US |
Child |
09293624 |
Apr 1999 |
US |