High-molecular weight conjugate of podophyllotoxins
AssigneeNippon Kayaku Kabushiki Kaisha
InventorsMasayuki Kitagawa, Keizou Ishikawa, Keiichirou Yamamoto, Kazutoshi Takashio, Masao Shibata
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Abstract
A novel podophyllotoxin derivative, which is capable of releasing a drug without depending on biological enzymes and can be expected to have an effective therapeutic effect and is soluble in water has been demanded. A polymer having a polyethyleneglycol structural unit and two or more succinic monoamide structural units, particularly a polymer conjugate of a podophyllotoxin in which a carboxylic acid group of polyethyleneglycol/polyaspartic acid copolymer and a hydroxyl group of podophyllotoxin and linked via an ester bond is provided.
Claims5
A high-molecular weight conjugate of podophyllotoxins, represented by formula (I):
- wherein R1 represents a hydrogen atom or a (C1-C6) alkyl group;
- R2 represents a linking group;
- R3 represents a hydrogen atom or a (C1-C6) acyl group;
- R4 represents the residue of a hydroxyl group of the podophyllotoxins;
- R5 represents a group selected from the group consisting of a (C1-C30) alkoxy group, a (C7-C30) aralkyloxy group, a (C1-C30) alkylamino group, a di(C1-C30) alkylamino group, an amino acid with a protected carboxyl group, and —N(R6)CONH(R7) wherein R6 and R7, which may be identical or different, each represent a (C3-C6) cyclic alkyl group or a (C1- C5) alkyl group optionally substituted with a tertiary amino group;
- t represents an integer from 5 to 11,500;
- d, e, f, g, h, i and j each independently represent an integer from 0 to 200, provided that d+e represents an integer from 1 to 200, and d+e+f+g+h+i+j represents an integer from 3 to 200, and that the respective constituent units of polyaspartic acid are bound in any order.
A high-molecular weight conjugate of podophyllotoxins, obtained by ester-bonding a carboxylic acid group of a polymer having a polyethylene glycol moiety and two or more succinic acid monoamide moieties to a hydroxyl group of the podophyllotoxins using a dehydrating condensing agent in an organic solvent.
Dependencies are inferred from the claim text.