CYCLOBUTANE AND METHYLCYCLOBUTANE DERIVATIVES AS JANUS KINASE INHIBITORS
The present invention relates to cyclobutane and methylcyclobutane derivatives, as well as their salts, compositions, and methods of use, which are Janus kinase (JAK) inhibitors useful in the treatment of JAK-associated diseases including, for example, inflammatory and autoimmune disorders, as well as cancer and myeloproliferative disorders.
1 . A compound which is 3-cyclobutyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof.
2 . The compound of claim 1 which is (R)-3-cyclobutyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof.
3 . The compound of claim 1 which is (S)-3-cyclobutyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof.
4 . A compound which is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(3-methylcyclobutyl)propanenitrile, or a pharmaceutically acceptable salt thereof.
5 . The compound of claim 4 which is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-((trans)-3-methylcyclobutyl)propanenitrile, or a pharmaceutically acceptable salt thereof.
6 . The compound of claim 5 which is (3R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-((trans)-3-methylcyclobutyl)propanenitrile, or a pharmaceutically acceptable salt thereof.
7 . The compound of claim 5 which is (3S)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-((trans)-3-methylcyclobutyl)propanenitrile, or a pharmaceutically acceptable salt thereof.
8 . The compound of claim 4 which is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-((cis)-3-methylcyclobutyl)propanenitrile, or a pharmaceutically acceptable salt thereof.
9 . The compound of claim 8 which is (3R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-((cis)-3-methylcyclobutyl)propanenitrile, or a pharmaceutically acceptable salt thereof.
10 . The compound of claim 8 which is (3S)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-((cis)-3-methylcyclobutyl)propanenitrile, or a pharmaceutically acceptable salt thereof.
11 . The phosphoric acid salt of the compounds of claim 1 or 4 .
12 . A composition comprising the compound of claim 1 or 4 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.
13 . A method of treating an autoimmune disease in a patient comprising administering to said patient a therapeutically effective amount of a compound of claim 1 or 4 , or a pharmaceutically acceptable salt thereof.
14 . A method of treating cancer in a patient comprising administering to said patient a therapeutically effective amount of a compound of any one of claim 1 or 4 , or a pharmaceutically acceptable salt thereof.
15 . A method of treating a myeloproliferative disorder in a patient comprising administering to said patient a therapeutically effective amount of a compound of claim 1 or 4 , or a pharmaceutically acceptable salt thereof.
16 . A method of treating an inflammatory disease in a patient comprising administering to said patient a therapeutically effective amount of a compound of any one of claim 1 or 4 , or a pharmaceutically acceptable salt thereof.
17 . A method of treating organ transplant rejection in a patient comprising administering to said patient a therapeutically effective amount of a compound of any one of claim 1 or 4 , or a pharmaceutically acceptable salt thereof.
18 . A method of treating dry eye in a patient comprising administering to said patient a therapeutically effective amount of a compound of any one of claim 1 or 4 , or a pharmaceutically acceptable salt thereof.