Prostacyclin compounds, compositions and methods of use thereof

Patent metadata

Field	Value
Publication number	US-9255064-B2
Application number	US-201514641104-A
Country	US
Kind code	B2
Filing date	Mar 6, 2015
Priority date	Oct 25, 2013
Publication date	Feb 9, 2016
Grant date	Feb 9, 2016

Abstract

Prostacyclin compounds and compositions comprising the same are provided herein. Specifically, prostacyclin compounds comprising treprostinil covalently linked to a linear C 5 -C 18 alkyl, branched C 5 -C 18 alkyl, linear C 2 -C 18 alkenyl, branched C 3 -C 18 alkenyl, aryl, aryl-C 1 -C 18 alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide) are described. The linkage, in one embodiment, is via a carbamate, amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. Methods for treating pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension are also provided.

First claim

The invention claimed is:

1. A prostacyclin compound of Formula (II), or a pharmaceutically acceptable salt thereof:

wherein R 1 is O;
R 2 is tetradecyl, pentadecyl, hexadecyl, heptadecyl or octadecyl; and
n is an integer from 0 to 5.

2. The prostacyclin compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 0 or 1.

3. The prostacyclin compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 0.

4. The prostacyclin compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 1.

5. The prostacyclin compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is tetradecyl.

6. The prostacyclin compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is pentadecyl.

7. The prostacyclin compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is hexadecyl.

8. The prostacyclin compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is heptadecyl.

9. The prostacyclin compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is octadecyl.

10. The prostacyclin compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein n is 1.

11. The prostacyclin compound of claim 6 , or a pharmaceutically acceptable salt thereof, wherein n is 1.

12. The prostacyclin compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein n is 1.

13. The prostacyclin compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein n is 1.

14. The prostacyclin compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein n is 1.

15. A prostacyclin compound of Formula (II), or a pharmaceutically acceptable salt thereof:

wherein n is 0, R 1 is NH or O and R 2 is a linear C 5 -C 18 alkyl.

16. The prostacyclin compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 1 is NH.

17. The prostacyclin compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 1 is O.

18. The prostacyclin compound of claim 16 , or a pharmaceutically acceptable salt thereof, wherein R 2 is a heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl or octadectyl.

19. The prostacyclin compound of claim 17 , or a pharmaceutically acceptable salt thereof, wherein R 2 is a heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl or octadectyl.

Assignees

• Insmed Inc

Inventors

• Malinin Vladimir
• Perkins Walter
• Leifer Franziska
• Konicek Donna
• Li Zhili
• Plaunt Adam

Classifications

• C07C69/734 Primary

  Ethers · CPC title

• A61K9/14

  Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)} · CPC title

• C07C235/22 Primary

  having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring · CPC title

• A61K9/0073

  Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; (nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M) · CPC title

• A61K47/544

  Phospholipids · CPC title