Drug compound and purification methods thereof

Patent metadata

Field	Value
Publication number	US-10519190-B2
Application number	US-201816053354-A
Country	US
Kind code	B2
Filing date	Aug 2, 2018
Priority date	Aug 3, 2017
Publication date	Dec 31, 2019
Grant date	Dec 31, 2019

Abstract

The invention provides a method of preparing a lyophilized pharmaceutical composition containing a compound described herein or a pharmaceutically-acceptable salt thereof. The process comprises dissolving the compound in a solvent comprising dimethylsulfoxide and optionally one or more co-solvents to form a solution, and then removing the solvent and any co-solvents by a freeze-drying process. Also provided by the invention are lyophilized pharmaceutical compositions and their use in medicine and in particular in the treatment of cancer.

First claim

What is claimed is:

1. A composition comprising:
a) a compound of the formula:

or a pharmaceutically acceptable salt thereof,
wherein the composition comprises at least 95% of the compound of Formula (1); and
b) a nucleotide-based compound that is not a compound of Formula (1), wherein the nucleotide-based compound is a compound of formula (2):

or a pharmaceutically acceptable salt thereof,
wherein:
R 1 is 4-amino-2H-1λ 2 ,3,5-triazin-2-one or a carbamide, each of which is independently substituted or unsubstituted;
each R 2 and R 3 is independently alkyl, which is substituted or unsubstituted; or hydrogen; and
R 4 is an acyl group, which is independently substituted or unsubstituted, or hydrogen.

2. The composition of claim 1 , wherein R 1 is a carbamide that is substituted.

3. The composition of claim 1 , wherein R 2 is H and R 3 is methyl substituted with methoxy.

4. The composition of claim 1 , wherein R 4 is hydrogen.

5. The composition of claim 1 , wherein R 4 is an acyl group.

6. The composition of claim 1 , wherein the compound of formula (2) is

7. The composition of claim 1 , wherein the compound of formula (2) is

8. The composition of claim 1 , wherein the compound of formula (2) is

9. The composition of claim 1 , wherein the compound of formula (2) is

10. A composition comprising:
a) a compound of the formula:

or a pharmaceutically acceptable salt thereof,
wherein the composition comprises at least 95% of the compound of Formula (1); and
b) a nucleotide-based compound that is not a compound of Formula (1), wherein the nucleotide-based compound is a compound of formula (3):

or a pharmaceutically acceptable salt thereof, wherein R 1 is heteroaryl or a carbamide, each of which is independently substituted or unsubstituted.

11. The composition of claim 10 , wherein R 1 is heteroaryl.

12. The composition of claim 11 , wherein R 1 is 4-amino-2H-1λ 2 ,3,5-triazin-2-one.

13. The composition of claim 10 , wherein R 1 is a carbamide that is substituted.

14. The composition of claim 10 , wherein the compound of formula (3) is

15. The composition of claim 10 , wherein the compound of formula (3) is

16. A composition comprising:
a) a compound of the formula:

or a pharmaceutically acceptable salt thereof,
wherein the composition comprises at least 95% of the compound of Formula (1); and
b) a nucleotide-based compound that is not a compound of Formula (1), wherein the nucleotide-based compound is a compound of formula (4):

or a pharmaceutically acceptable salt thereof, wherein R 1 is heteroaryl, which is substituted or unsubstituted; and R 5 is hydroxy or a nucleotide.

17. The composition of claim 16 , wherein R 1 is heteroaryl that is substituted.

18. The composition of claim 17 , wherein R 1 is 4-amino-2H-1λ 2 ,3,5-triazin-2-one.

19. The composition of claim 17 , wherein R 1 is 2-amino-9λ 2 -purin-6(1H)-one.

20. The composition of claim 16 , wherein R 5 is hydroxy.

21. The composition of claim 16 , wherein R 5 is a nucleotide.

22. The composition of claim 21 , wherein the nucleotide has the formula:

23. The composition of claim 16 , wherein the compound of formula (4) is

24. The composition of claim 16 , wherein the compound of formula (4) is

Assignees

• Otsuka Pharma Co Ltd

Inventors

• Joshi-Hangal Rajashree
• Davar Nipun
• Priebe Stephen R

Classifications

• A61K31/7084 Primary

  Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide · CPC title

• F26B5/06

  the process involving freezing · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07H19/173

  with 2-deoxyribosyl as the saccharide radical · CPC title

• A61K9/19

  lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} · CPC title