Metabolites of the Janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
View Patent ↗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.
1. 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-I-yl)-3-(3-oxocyclopentyl) propanenitrile,
or a pharmaceutically acceptable salt thereof;
which is substantially isolated.
2. A composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.
3. The composition of claim 2 which is suitable for oral administration.
4. A method of treating a disease in a patient, wherein said disease is associated with Janus kinase activity, comprising administering to said patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said disease is allograft rejection or graft versus host disease.
5. A composition according to claim 2 , containing at least about 50% by weight of said compound or said salt.
6. A composition according to claim 2 , containing at least about 90% by weight of said compound or said salt.
7. A composition according to claim 2 , containing at least about 95% by weight of said compound or said salt.
8. A composition according to claim 2 , containing at least about 99% by weight of said compound or said salt.
9. A compound according to claim 1 , which is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(3-hydroxycyclopentyl)propanenitrile, or a pharmaceutically acceptable salt thereof.
10. A compound according to claim 1 , which is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(2-hydroxycyclopentyl)propanenitrile, or a pharmaceutically acceptable salt thereof.
11. A compound according to claim 1 , which is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(3-oxocyclopentyl)propanenitrile, or a pharmaceutically acceptable salt thereof.