Therapeutic dendrimers

Patent metadata

Field	Value
Publication number	US-10314920-B2
Application number	US-201815899892-A
Country	US
Kind code	B2
Filing date	Feb 20, 2018
Priority date	Feb 22, 2017
Publication date	Jun 11, 2019
Grant date	Jun 11, 2019

Abstract

Disclosed are dendrimers of formula (I):

and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions comprising the dendrimer of formula (I) and methods of using the same for treating cancer.

First claim

The invention claimed is:

1. A dendrimer of formula (IV):

or a pharmaceutically acceptable salt thereof,
wherein
Y is PEG 1800-2400 or H;
Q is H or L-AA, in which L-AA has the structure:

and
A is —N(CH 3 ),
provided that if the sum of PEG 1800-2400 and L-AA is less than 64, the remaining Q and Y moieties are H, and provided that at least one Q is L-AA.

2. A dendrimer of formula (V):

or a pharmaceutically acceptable salt thereof, wherein
Y is PEG 1800-2400 or H;
Q is H or L-AA, wherein L-AA has the structure:

A is —N(CH 3 ),
provided that if the sum of PEG 1800-2400 and L-AA is less than 64, the remaining Q and Y moieties are H, and provided that at least one Q is L-AA.

3. The dendrimer of claim 1 or 2 , or a pharmaceutically acceptable salt thereof, wherein the sum of PEG 1800-2400 and L-AA is an integer between 50 and 64.

4. The dendrimer of claim 3 , or a pharmaceutically acceptable salt thereof, wherein the sum of PEG 1800-2400 and L-AA is an integer between 58 and 64.

5. The dendrimer of claim 1 or 2 , or a pharmaceutically acceptable salt thereof, wherein the dendrimer has between 25 and 32 PEG 1800-2400 .

6. The dendrimer of claim 5 , or a pharmaceutically acceptable salt thereof, wherein the dendrimer has between 29 and 32 PEG 1800-2400 .

7. The dendrimer of claim 1 or 2 , or a pharmaceutically acceptable salt thereof, wherein the dendrimer has between 25 and 32 L-AA.

8. The dendrimer of claim 7 , or a pharmaceutically acceptable salt thereof, wherein the dendrimer has between 29 and 32 L-AA.

9. The dendrimer of claim 1 or 2 , or a pharmaceutically acceptable salt thereof, wherein the dendrimer has between 0 and 14 hydrogens at the Q and/or Y positions.

10. The dendrimer of claim 9 , or a pharmaceutically acceptable salt thereof, wherein the dendrimer has between 0 and 6 hydrogens at the Q and/or Y positions.

11. The dendrimer of claim 1 or 2 , or a pharmaceutically acceptable salt thereof, wherein the PEG has an average molecular weight of between about 2000 and 2200 Da.

12. The dendrimer of claim 1 or 2 , or a pharmaceutically acceptable salt thereof, wherein the PEG has a PDI of between about 1.00 and 1.10.

13. The dendrimer of claim 12 , or a pharmaceutically acceptable salt thereof, wherein the PEG has a PDI of about 1.05.

14. The dendrimer of claim 1 or 2 , or a pharmaceutically acceptable salt thereof, wherein the dendrimer has a molecular weight of between about 90 and 120 kDa.

15. The dendrimer of claim 14 , or a pharmaceutically acceptable salt thereof, wherein the dendrimer has a molecular weight of between about 103 and 107 kDa.

16. A pharmaceutical composition comprising a dendrimer of claim 1 or 2 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, carrier or diluent.

Assignees

• Astrazeneca Ab

Inventors

• Ashford Marianne Bernice
• Grant Iain
• Hennessy Edward John
• Mccoull William
• Giannis Michael
• Kelly Brian
• Owen David
• Secrist John Paul

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/60

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

• C08G69/40

  Polyamides containing oxygen in the form of ether groups (C08G69/12, C08G69/32 take precedence) · CPC title

• C08G83/003 Primary

  Dendrimers · CPC title

• A61K31/451 Primary

  having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine · CPC title