Temozolomide compounds, polymers prepared therefrom, and method of treating a disease

Patent metadata

Field	Value
Publication number	US-12338244-B2
Application number	US-202418408929-A
Country	US
Kind code	B2
Filing date	Jan 10, 2024
Priority date	Sep 22, 2016
Publication date	Jun 24, 2025
Grant date	Jun 24, 2025

Abstract

A temozolomide compound according to formula (I)is described, wherein R1, L1, and X are defined herein. The temozolomide compound can be used to prepare polymers comprising temozolomide. Additionally, the polymers comprising temozolomide can be particularly useful in the treatment of certain diseases.

First claim

The invention claimed is:

1. A polymer comprising repeating units comprising temozolomide derived from a temozolomide compound, wherein the repeating units comprising temozolomide are of formula (IV):

wherein
R 4 is independently at each occurrence a hydrogen or a C 1-6 alkyl group;
Y is independently at each occurrence —O— or —NH—;
L 3 is independently at each occurrence a divalent C 1-12 alkylene group, di(C 1-12 ) alkylene disulfide group, C 1-12 alkylene ester group, C 6-20 arylene group, or C 1-20 alkylene oxide group;
Z is independently at each occurrence a disulfide group or an amide group;
L 1 is independently at each occurrence a divalent C 1-12 alkylene group, di(C 1-12 alkylene) disulfide group, C 1-12 alkylene ester group, C 6-20 arylene group, C 1-20 alkylene oxide group, or C 1-12 alkylene sulfide group;
X is independently at each occurrence —O— or —NH—; and
p is independently at each occurrence 0 or 1.

2. The polymer of claim 1 , further comprising repeating units of formula (II)

wherein
R 2 is a hydrogen or a C 1-6 alkyl group;
V is —O— or —NH—; and
R 3 is a zwitterionic group, a poly (C 1-6 alkylene oxide) group, a hydroxy-substituted C 1-6 alkyl group, or a C 1-12 alkyl group.

3. The polymer of claim 1 , further comprising repeating units of formula (III)

wherein
R 2 is a hydrogen or a C 1-6 alkyl group; and
R 6 is a C 6-20 aryl group.

4. The polymer of claim 1 , wherein
X is —O—; and
L 1 is a divalent C 1-6 alkylene group.

5. The polymer of claim 2 , wherein in formula (II), R 3 is a zwitterion having the structure -L 2 -A-B—C;
wherein
L 2 is a divalent C 1-12 alkylene group, C 6-20 arylene group, or C 1-20 alkylene oxide group;
A is a center of permanent positive charge or a center of permanent negative charge;
B is a divalent group comprising a C 1-12 alkylene group, a C 6-30 arylene or heteroarylene group, or a C 1-20 alkylene oxide group; and
C is a center of permanent positive charge or a center of permanent negative charge, provided that the zwitterion has an overall net charge of zero.

6. The polymer of claim 2 , wherein in formula (II), R 3 is a zwitterionic group of the formula

7. The polymer of claim 2 , wherein the polymer is a copolymer comprising repeating units of formula (II) and (IV), wherein
in each occurrence of the repeating units of formula (II),
R 2 is a methyl group
V is —O—; and

R 3 is a phosphorylcholine group having the structure

and
in each occurrence of the repeating units of formula (IV),
R 4 is a methyl group;
Y is —O—;
p is 0;
L 1 is a divalent di(C 1-6 alkylene) disulfide group; and
X is —O—.

8. The polymer of claim 2 , wherein the polymer is a copolymer comprising repeating units of formula (II) and (IV), wherein
in each occurrence of the repeating units of formula (II),
R 2 is a methyl group;

V is —O—; and
R 3 is a phosphorylcholine group having the structure

and
in each occurrence of the repeating units of formula (IV),
R 4 is a methyl group;
Y is —O—;
p is 1;
L 3 is a divalent C 1-12 alkylene group;
Z is a disulfide group;
L 1 is a divalent C 1-6 alkylene group; and
X is —O—.

9. The polymer of claim 1 , wherein the polymer comprises 1 to 100 mole percent of repeating units comprising temozolomide based on the total repeating units of the polymer.

10. The polymer of claim 1 , wherein the polymer comprises 10 to 55 mole percent of repeating units comprising temozolomide based on the total repeating units of the polymer.

Assignees

• Univ Massachusetts

Inventors

• Emrick Todd
• Skinner Matthew
• Ward Sarah M
• Saha Banishree

Classifications

• C08F220/365

  containing further carboxylic moieties · CPC title

• A61K47/58

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin · CPC title

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• C08G65/32

  Polymers modified by chemical after-treatment · CPC title

• A61K47/545

  Heterocyclic compounds (A61K47/558 takes precedence) · CPC title