Prodrugs of etoposide and etoposide analogs
AssigneeNobex Corporation
InventorsNnochiri Ekwuribe, Christopher H. Price, Tatyana A. Dyakonov
Life of this patent
Estimating the term…
Abstract
The present invention provides amphiphilic prodrugs comprising a therapeutic compound conjugated to an PEG-oligomer/polymer and methods for using said prodrugs to enable oral drug delivery and/or delivery of drugs across the blood brain barrier into the central nervous system.
Claims105
A prodrug comprising:
- (a) at least one therapeutic compound;
- and
- (b) one or more PEG polymers and/or oligomers, each joined to a bonding site on the therapeutic compound by a hydrolyzable bond, said PEG polymers and/or oligomers each:
- (i) comprising a straight or branched PEG segment consisting of 2 to 25 polyethylene glycol units;
- and
- (ii) comprising a salt-forming moiety.
A prodrug comprising a therapeutic compound joined by hydrolysable bond(s) to one or more PEG oligomer(s) selected from the group consisting of:
- wherein n is from 1 to 7, m is from 2 to 25, and R is hydrogen or a lower alkyl;
- wherein n is from 1 to 6, p is from 2 to 8, m is from 2 to 25, and R is hydrogen or a lower alkyl;
- wherein n is from 1 to 6, m and r are each independently from 2 to 25, and R is hydrogen or a lower alkyl;
- wherein n is from 1 to 6, p is from 2 to 8, m is from 2 to 25 and R is hydrogen or lower alkyl;
- wherein n is from 1 to 6, p is from 2 to 25, m is from 2 to 8, R is hydrogen or lower alkyl, and X is a negative ion;
- wherein n is from 1 to 6, p is from 2 to 8, m is from 2 to 25, and R1 and R2 are each independently lower alkyl;
- wherein n is from 1 to 6, p is from 2 to 8 and m is from 2 to 25;
- wherein n is from 1 to 5, m is from 2 to 25, X− is a negative ion, and wherein R1 and R2 are each independently hydrogen or lower alkyl;
- and
- wherein n is from 1 to 6, m is from 2 to 25 and X− is a negative ion.
A prodrug comprising a therapeutic compound joined by hydrolyzable bond(s) to one or more PEG oligomer(s) having the formula:
- wherein n and p are each independently from 1 to 6, m is from 2 to 25 and X+ is a positive ion.
An epipodophyllotoxin prodrug in salt form comprising:
- (a) an epipodophyllotoxin;
- (b) an oligomer joined to a bonding site on the epipodophyllotoxin by a hydrolyzable bond, said oligomer comprising:
- (i) a straight or branched PEG segment consisting of 2 to 25 polyethylene glycol units;
- and
- (ii) a salt forming moiety;
- and
- (c) a positive or negative ion associated with the salt forming moiety to provide the epipodophyllotoxin prodrug in salt form.
A epipodophyllotoxin prodrug in salt form comprising:
- (a) an epipodophyllotoxin;
- (b) an oligomer joined to a bonding site on the epipodophyllotoxin by a hydrolyzable bond, wherein the oligomer is:
- wherein n is from 1 to 6, p is from 2 to 8, m is from 2 to 25, R is hydrogen or lower alkyl, and X− is a negative ion.
An epipodophyllotoxin prodrug in salt form comprising:
- (a) an epipodophyllotoxin;
- (b) an oligomer joined to a bonding site on the epipodophyllotoxin by a hydrolyzable bond, wherein the oligomer is:
- wherein n is from 1 to 5, m is from 2 to 25, X− is a negative ion, and wherein R1 and R2 are each independently hydrogen or lower alkyl.
An epipodophyllotoxin prodrug in salt form comprising:
- (a) an epipodophyllotoxin;
- (b) an oligomer joined to a bonding site on the epipodophyllotoxin by a hydrolyzable bond, wherein the oligomer is:
- wherein n is from 1 to 6, m is from 2 to 25 and X− is a negative ion.
An etoposide prodrug comprising:
- (a) an etoposide;
- (b) an oligomer joined to a bonding site on the etoposide by a hydrolyzable bond, said oligomer comprising a straight or branched PEG segment consisting of 2 to 25 polyethylene glycol units.
An etoposide prodrug comprising:
- (a) an etoposide;
- and
- (b) an oligomer joined to a bonding site on the etoposide by a hydrolyzable bond, said oligomer comprising a straight or branched PEG segment consisting of 1 to 25 polyethylene glycol units.
An etoposide prodrug comprising:
- (a) an etoposide therapeutic compound selected from the group consisting of etoposide and an etoposide analog which retains some or all of the therapeutic activity of etoposide;
- and
- (b) an oligomer joined to a bonding site on the etoposide therapeutic compound by a hydrolyzable bond, said oligomer comprising a straight or branched PEG segment consisting of 1 to 25 polyethylene glycol units.
An etoposide prodrug comprising an etoposide coupled at each of the three hydroxy bonding sites of the etoposide to an oligomer having the following structure:
An etoposide prodrug comprising an etoposide coupled at each of the three hydroxy bonding sites of the etoposide to an oligomer having the following structure:
An etoposide prodrug comprising an etoposide coupled at each of the three hydroxy bonding sites of the etoposide to an oligomer having the following structure:
Dependencies are inferred from the claim text.