Claims
- 1. A polymer conjugate comprising a water soluble and non-peptidic polymer covalently attached to a protein kinase C inhibitor.
- 2. The polymer conjugate of claim 1, wherein the water soluble and non-peptidic polymer is covalently attached via a hydrolytically degradable linkage to the protein kinase C inhibitor.
- 3. The polymer conjugate of claim 2, wherein the hydrolytically degradable linkage is selected from the group consisting of carboxylate ester, phosphate ester, anhydride, acetal, ketal, acyloxyalkyl ether, imine, orthoester, and oligonucleotide.
- 4. The polymer conjugate of claim 1, wherein the polymer is selected from the group consisting of poly(alkylene glycol), poly(oxyethylated polyol), poly(olefinic alcohol), poly(vinylpyrrolidone), poly(hydroxyalkylmethacrylamide), poly(hydroxyalkylmethacrylate), poly(saccharides), poly(α-hydroxy acid), poly(vinyl alcohol), polyphosphazene, polyoxazoline, poly(N-acryloylmorpholine), and copolymers, terpolymers, and mixtures thereof.
- 5. The polymer conjugate of claim 1, wherein the polymer is poly(ethylene glycol).
- 6. The polymer conjugate of claim 1, wherein the protein kinase C inhibitor selectively inhibits the alpha, beta, or gamma protein kinase C isozyme.
- 7. The polymer conjugate of claim 1, wherein the protein kinase C inhibitor is a indolylmaleimide or indazolyl-substituted pyrroline molecule.
- 8. The polymer conjugate of claim 1, wherein the protein kinase C inhibitor is a indolylmaleimide molecule and the polymer is attached to a carbon atom of an indole ring or the nitrogen atom of the maleimide ring.
- 9. The polymer conjugate of claim 8, wherein the indolylmaleimide molecule has the structure:
- 10. The polymer conjugate of claim 9, wherein Y and R2 are hydrogen and each R is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, alkylamino, alkylaminoalkyl, dialkylaminoalkyl, trialkylaminoalkyl, aminoalkylaminoalkyl, azidoalkyl, acylaminoalkyl, acylthioalkyl, alkylsulphonylaminoalkyl, arylsulphonylaminoalkyl, mercaptoalkyl, alkylthioalkyl, alkylsuphinylalkyl, alkylsulphonylalkyl, alkylsulphonyloxyalkyl, alkylcarbonyloxyalkyl, cyanoalkyl, amidinoalkyl, isothiocyanatoalkyl, glucopyranosyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, hydroxyalkylthioalkyl, mercaptoalkylthioalkyl, arylthioalkyl, carboxyalkylthioalkyl, alkyl-S(C═NH)NH2, and alkyl-NC(═NNO2)NH2.
- 11. The polymer conjugate of claim 1, having the structure:
- 12. The polymer conjugate of claim 11, wherein POLY is poly(ethylene glycol).
- 13. The polymer conjugate of claim 11, wherein X is selected from the group consisting of —CONH—, —C(O)—, —O—(CH2)n—C(O)—O— where n is 1-10, —O—(CH2)n—C(O)—NH— wherein n is 1-10, —C(O)—O—(CH2)n—C(O)—NH— where n is 1-10, and —O—CH2—C(O)O—CH2—C(O)—NH—.
- 14. The polymer conjugate of claim 11, having the structure:
- 15. The polymer conjugate of claim 11, having the structure:
- 16. The polymer conjugate of claim 1, having the structure:
- 17. The polymer conjugate of claim 16, wherein R′ is a residue of a central core molecule selected from the group consisting of glycerol, glycerol oligomers, pentaerythritol, sorbitol, and lysine.
- 18. The polymer conjugate of claim 16, wherein each POLY is poly(ethylene glycol).
- 19. The polymer conjugate of claim 1, wherein the polymer is linear or branched.
- 20. A pharmaceutical composition, comprising:
a polymer conjugate comprising a water soluble and non-peptidic polymer covalently attached to a protein kinase C inhibitor, and a pharmaceutically acceptable carrier.
- 21. The pharmaceutical composition of claim 20, wherein the polymer is selected from the group consisting of poly(alkylene glycol), poly(oxyethylated polyol), poly(olefinic alcohol), poly(vinylpyrrolidone), poly(hydroxyalkylmethacrylamide), poly(hydroxyalkylmethacrylate), poly(saccharides), poly(α-hydroxy acid), poly(vinyl alcohol), polyphosphazene, polyoxazoline, poly(N-acryloylmorpholine), poly(acrylic acid), carboxymethyl cellulose, hyaluronic acid, hydroxypropylmethyl cellulose and copolymers, terpolymers, and mixtures thereof.
- 22. The pharmaceutical composition of claim 20, wherein the polymer is poly(ethylene glycol).
- 23. The pharmaceutical composition of claim 20, wherein the protein kinase C inhibitor selectively inhibits the alpha, beta, or gamma protein kinase C isozyme.
- 24. The pharmaceutical composition of claim 20, wherein the protein kinase C inhibitor is a indolylmaleimide or indazolyl-substituted pyrroline molecule.
- 25. The pharmaceutical composition of claim 20, wherein the protein kinase C inhibitor is a indolylmaleimide molecule and the polymer is attached to a carbon atom of either indole ring or the nitrogen atom of the maleimide ring.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of priority of Provisional Application Serial No. 60/340,535, filed Oct. 29, 2001, which is incorporated herein by reference in its entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60340535 |
Oct 2001 |
US |