Metabolites of the janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile

Patent metadata

Field	Value
Publication number	US-10463667-B2
Application number	US-201715496824-A
Country	US
Kind code	B2
Filing date	Apr 25, 2017
Priority date	Jun 13, 2007
Publication date	Nov 5, 2019
Grant date	Nov 5, 2019

Abstract

The present invention provides active metabolites of 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases including, for example, immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases.

First claim

What is claimed is:

1. A method of treating a disease selected from allograft rejection and graft versus host disease in a patient in need thereof, comprising administering to the patient a pharmaceutical composition comprising a compound selected from:
3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(3-hydroxycyclopentyl)propanenitrile;
3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(2-hydroxycyclopentyl)propanenitrile; and
3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(3-oxycyclopentyl)propanenitrile,
or a pharmaceutically acceptable salt thereof,
and a pharmaceutically acceptable carrier.

2. The method of claim 1 , wherein the disease is graft versus host disease.

3. The method of claim 2 , wherein about 5 to about 1000 mg of the compound, or pharmaceutically acceptable salt thereof, is administered to the patient.

4. The method of claim 2 , further comprising administering to the patient at least one additional therapeutic agent.

5. The method of claim 4 , wherein the therapeutic agent is administered to a patient simultaneously or sequentially.

6. The method of claim 4 , wherein said therapeutic agent is an immunosuppressant.

7. The method of claim 4 , wherein said therapeutic agent is a steroid.

8. The method of claim 4 , wherein said therapeutic agent is a corticosteroid.

9. The method of claim 8 , wherein said corticosteroid is dexamethasone or prednisone.

10. The method of claim 8 , wherein said corticosteroid is dexamethasone.

11. The method of claim 8 , wherein said corticosteroid is prednisone.

12. The method of claim 1 , wherein the disease is allograft rejection.

13. The method of claim 12 , wherein about 5 to about 1000 mg of the compound, or pharmaceutically acceptable salt thereof, is administered to the patient.

14. The method of claim 12 , further comprising administering to the patient at least one additional therapeutic agent.

15. The method of claim 14 , wherein the therapeutic agent is administered to a patient simultaneously or sequentially.

16. The method of claim 14 , wherein said therapeutic agent is an immunosuppressant.

17. The method of claim 14 , wherein said therapeutic agent is a steroid.

18. The method of claim 14 , wherein said therapeutic agent is a corticosteroid.

19. The method of claim 18 , wherein said corticosteroid is dexamethasone or prednisone.

20. The method of claim 18 , wherein said corticosteroid is dexamethasone.

21. The method of claim 18 , wherein said corticosteroid is prednisone.

22. The method of claim 1 , wherein the compound is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(3-hydroxycyclopentyl)propanenitrile.

23. The method of claim 1 , wherein the compound is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(2-hydroxycyclopentyl)propanenitrile.

24. The method of claim 1 , wherein the compound is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(3-oxycyclopentyl)propanenitrile.

25. The method of claim 1 , wherein the pharmaceutical composition is suitable for oral administration.

26. The method of claim 1 , wherein the pharmaceutical composition is in tablet form.

Assignees

• Incyte Corp
• Incyte Holdings Corp
• Incyte Inc

Inventors

• Rodgers James D
• Arvanitis Argyrios G
• Shi Jack Guoen
• Shepard Stacey

Classifications

• C07D487/04

  Ortho-condensed systems · CPC title

• A61K31/519 Primary

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• C12N9/99

  Enzyme inactivation by chemical treatment · CPC title