PYRROLO[2,3-D]PYRIMIDINE UREA COMPOUNDS AS JAK INHIBITORS
The present invention provides pyrrolo{2,3-d}pyrimidine compounds, their use as Janus Kinase (JAK) inhibitors, pharmaceutical compositions containing this compounds, and methods for the preparation of these compounds.
1 . A compound of formula I:
or a pharmaceutically acceptable salt thereof wherein R 1 is H or —C 1-4 alkyl; and R 2 is a thiadiazole group optionally substituted with —OH or —OCH 3 .
2 . A compound of claim 1 which is a compound of formula IA
or a pharmaceutically acceptable salt thereof.
3 . A compound of claim 1 wherein R 1 is methyl.
4 . A compound of claim 1 wherein R 2 is 1,3,4-thiadiazol-2-yl.
5 . A compound of claim 1 wherein R 2 is 3-methoxy-1,2,4-thiadiazol-5-yl.
6 . A compound of claim 1 which is (3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-N-(1,3,4-thiadiazol-2-yl)piperidine-1-carboxamide.
7 . A compound of claim 1 which is (3R,4R)-N-(3-methoxy-1,2,4-thiadiazol-5-yl)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidine-1-carboxamide.
8 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
9 . A method for treating allergic reactions, allergic dermatitis, atopic dermatitis, eczema, or pruritus in a mammal comprising administering to a mammal in need a therapeutically effective amount of a compound of claim 1 .
10 . The method of claim 9 wherein the therapeutically effective amount is from 0.01 mg/kg of body weight/day to 100 mg/kg of body weight/day.
11 . The method of claim 9 wherein the therapeutically effective amount is from 0.1 mg/kg of body weight/day to 10 mg/kg of body weight/day.
12 . The method of claim 9 wherein the therapeutically effective amount is from 0.2 mg/kg of body weight/day to 1.5 mg/kg of body weight/day.
13 . The method of claim 9 wherein the mammal comprises a companion animals.
14 . The method of claim 3 wherein the companion animals is a dog.
15 . The method of claim 9 wherein the mammal comprises livestock.
16 . The method of claim 9 wherein the compound of formula 1 is administered orally, parenterally, or topically.
17 . A method for treating neurodegenerative diseases, keratoconjunctivitis, chronic respiratory diseases, autoimmune diseases, inflammatory bowel disease, neoplasia and arthritic conditions in a mammal comprising administering to a mammal in need a therapeutically effective amount of a compound of claim 1 .