Pyrrolopyrimidine and pyrrolopyridine derivatives
The present invention relates to pyrrolopyrimidine compounds according to Formula I and their use in the prophylaxis and/or treatment of pain, inflammatory conditions, cardiovascular diseases, neurodegenerative diseases, neurological diseases, complications of type I diabetes, cancer and/or fibrotic diseases. In a particular aspect, the present compounds are ASK inhibitors, particularly ASK1 inhibitors. The present invention also provides methods for the production of a compound of the invention, pharmaceutical compositions comprising a compound of the invention, the use of the compounds in the prophylaxis and/or treatment of pain, inflammatory conditions, cardiovascular diseases, neurodegenerative diseases, neurological diseases, complications of type I diabetes, cancer and/or fibrotic diseases.
1. A compound according to Formula I:
wherein
R 1 is H, CH 3 , F or Cl;
X is N, CH or C—CN; and
R 2 is CH 3 or halogen;
or a pharmaceutically acceptable salt, or a solvate, or a pharmaceutically acceptable salt of a solvate thereof.
2. The compound, or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 1 is F.
3. The compound, or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 2 is CH 3 .
4. The compound, or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein X is CH.
5. The compound, or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein X is C—CN.
6. The compound, or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein X is N.
7. The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is:
2-amino-5-fluoro-N-[1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidyl]pyridine-4-carboxamide, 2-amino-5-methyl-N-[1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidyl]pyridine-4-carboxamide, 2-amino-5-chloro-N-[1-(5-methyl-7H-pyrrolo[2,3-d] pyrimidin-4-yl)-4-piperidyl]-pyridine-4-carboxamide, 2-amino-N-[1-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidyl] pyridine-4-carboxamide, 2-amino-N-[1-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidyl]-5-fluoro-pyridine-4-carboxamide, 2-amino-N-[1-(5-cyano-3-methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperidyl]-5-fluoro-pyridine-4-carboxamide, or 2-amino-N-[1-(3-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)-4-piperidyl]-5-fluoro-pyridine-4-carboxamide.
8. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof according to claim 1 , and a pharmaceutically acceptable carrier.
9. A method for treatment of pain, inflammatory conditions, arthritis, rheumatoid arthritis, osteoarthritis, liver fibrosis, pulmonary fibrosis, steatohepatitis, and/or NASH comprising administering an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 1 to an individual in need thereof.
10. A process for preparing a compound of formula I or a pharmaceutically acceptable salt, or a solvate, or a pharmaceutically acceptable salt of a solvate thereof, according to claim 1 , which comprises:
(a) reacting a compound of formula II:
wherein X and R 2 are as defined in claim 1 , with a compound of formula III:
or a protected derivative thereof, wherein R 1 is as defined in claim 1 ;
(b) deprotecting a protected derivative of a compound of formula I;
(c) interconverting a compound of formula I or protected derivative thereof to a further compound of formula I or protected derivative thereof; and
(d) optionally forming a pharmaceutically acceptable salt of a compound of formula I.
11. A method for treatment of pain, inflammatory conditions, arthritis, rheumatoid arthritis, osteoarthritis, liver fibrosis, pulmonary fibrosis, steatohepatitis, and/or NASH comprising administering a pharmaceutical composition according to claim 8 to an individual in need thereof.
12. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt thereof according to claim 7 , and a pharmaceutically acceptable carrier.
13. A method for treatment of pain, inflammatory conditions, arthritis, rheumatoid arthritis, osteoarthritis, liver fibrosis, pulmonary fibrosis, steatohepatitis, and/or NASH comprising administering an effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 7 to an individual in need thereof.
14. A method for treatment of pain, inflammatory conditions, arthritis, rheumatoid arthritis, osteoarthritis, liver fibrosis, pulmonary fibrosis, steatohepatitis, and/or NASH comprising administering a pharmaceutical composition according to claim 12 to an individual in need thereof.