Metabolites of the janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile
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 method of treating cancer in a patient, comprising administering to said patient a therapeutically effective amount of a compound selected from the group consisting of:
3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-y1)-1H-pyrazol-1-y1)-3-(3-hydroxycyclopentyl)propanenitrile;
3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-y1)-1H-pyrazol-1-y1)-3-(2-hydroxycyclopentyl)propanenitrile; and
3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-y1)-1H-pyrazol-1-y1)-3-oxocyclopentyl)propanenitrile,
or a pharmaceutically acceptable salt thereof;
wherein said cancer is pancreatic cnacer, chronic myelogenous leukemia (CML), acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), or chronic myelomonocytic leukemia (CMML); and
wherein said treating refers to ameliorating or inhibiting the disease in a patient.
2. A method of treating myeloid metaplasia with myelofibrosis (MMM), polycythemia vera (PV), or essential thrombocythemia (ET) in a patient, comprising administering to said patient a therapeutically effective amount of a compound selected from the group consisting of:
3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-y1)- 1H-pyrazol-1-y1)-3-(3-hydroxycyclopentyl)propanenitrile;
3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-y1)-1H-pyrazol-1-y1)-3-(2-hydroxycyclopentyl)propanenitrile; and
3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-y1)-1H-pyrazol-1-y1)-3-(3oxocyclopentyppropanenitrile,
or a pharmaceutically acceptable salt thereof, wherein said treating refers to ameliorating or inhibiting the disease in a patient.
3. The method of claim 1 , wherein said cancer is chronic myelogenous leukemia (CML) or acute myelogenous leukemia (AML).
4. The method of claim 1 , wherein said cancer is acute lymphoblastic leukemia (ALL).
5. The method of claim 1 , wherein said cancer is chronic myelomonocytic leukemia (CMML).
6. The method of claim 1 , wherein said cancer is pancreatic cancer.