US 2006/0223809 A1 · Novel compounds

Abstract

The invention relates to thienopyridazinones of formula (I): wherein: R1 is C1-6 alkyl, C2-6 alkenyl or C3-6 cycloalkyl which is optionally substituted by C1-6 alkyl, each of the above being optionally substituted by one or more halogen atoms; R2 is C1-6 alkyl; R3 is a group CO-G or SO2-G where G is a 5- or 6-membered ring containing a nitrogen atom and a second heteroatom selected from oxygen and sulphur adjacent to the nitrogen, and optionally substituted by up to 3 groups selected from hydroxyl and C1-4 alkyl; Q is CR5R6 where R5 and R6 are as defined in the specification; and R4 is a 5- to 10-membered mono- or bi-cyclic aromatic ring system, containing 0 to 4 heteroatoms independently selected from nitrogen, oxygen and sulphur, the ring system being optionally substituted as described in the specification, and pharmaceutically acceptable salts and solvates thereof. Processes for their preparation, pharmaceutical compositions containing them and their use in therapy, in particular in the modulation of autoimmune disease are also described.

Claims5

Dependent claims

1-15. (canceled)

A method of effecting immunosuppression which comprises administering to a patient a therapeutically effective amount of a compound selected from the group consisting of

2-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-3-[[(4S)-4-hydroxy-2-isoxazolidinyl]carbonyl-5-methyl-7-(1-methylethyl)thieno[2,3,-d]pyridazin-4(5H)-one,
2-[(3,5-Dimethyl-1H-pyrazol-4-yl)methyl]-3-[[(4S)-4-hydroxy-2-isoxazolidinyl]carbonyl]-5-methyl-7-(2-methylpropyl)thieno[2,3-d]pyridazin-4(5H)-one,
2-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-7-ethyl-3-[[(4S)-4-hydroxy-2-isoxazolidinyl]carbonyl]-5-methyl-thieno[2,3-d]pyridazin-4(5H)-one,
7-Cyclopropyl-2[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-3-[[(4S)-4-hydroxy-2-isoxazolidinyl]carbonyl]-5-methyl-thieno[2,3-d]pyridazin-4(5H)-one,
7-Cyclopropyl-2-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-5-ethyl-3-[[(4S)-4-hydroxy-2-isoxazolidinyl]carbonyl]-thieno[2,3-d]pyridazin-4(5H)-one,
2-[(3,5-Dimethyl-1H-pyrazol-4-yl)methyl]-3-[[(4S)-4-methyl-2-isoxazolidinyl]carbonyl-5-methyl-7-(1-methylethyl)thieno[2,3,-d]pyridazin-4(5H)-one,
2-[(3,5-Dimethyl-1H-pyrazol-4-yl)methyl]-3-[[(4S)-4-hydroxy-4-methyl-2-isoxazolidinyl]carbonyl]-5-methyl-7-(2-methylpropyl)-thieno[2,3,-d]pyridazin-4(5H)-one,
2-[(3,5-Dimethyl-1H-pyrazol-40yl)methyl]-7-ethyl-3-[[(4S)-4-hydroxy-4-methyl-2-isoxazolidinyl]carbonyl]-5-methyl-thieno[2,3-d]pyridazin-4(5H)-one,
7-Cyclopropyl-2-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-3-[[(4S)-4-hydroxy-4-methyl-2-isoxazolidinyl]carbonyl]-5-methyl-thieno[2,3-d]pyridazin-4(5H)-one,
3-[[(4S)-4-hydroxyisoxazolidinyl]carbonyl-5-methyl-7-(2-methylpropyl)-2-(1H-pyrrolo[2,3-b]pyridine-3-ylmethyl)thieno[2,3,-d]pyridazin-4(5H)-one,
3-[[(4S)-4-Hydroxy-2-isoxazolidinyl]carbonyl]-5-methyl-7-(2-methylpropyl)-2-[(1,3,5-trimethylpyrazol-4-yl)methyl]-thieno[2,3,-d]pyridazin-4(5H)-one,
2-[[3,5-dimethyl-1-(2-pyridinyl)-1H-pyrazol-4-yl]methyl]-7-ethyl-3-[[(4S)-4-hydroxy-2-isoxazolidinyl]carbonyl]-5-methyl-thieno[2,3-d]pyridazin-4(5H)-one,
2-[[3,5-Dimethyl-1-(2-pyridinyl)-1H-pyrazol-4-yl]methyl]-7-ethyl-3-[[(4S)-4-hydroxy-4-methyl-2-isoxazolidinyl]carbonyl]-5-methyl-thieno[2,3-d]pyridazin-4(5H)-one,
7-Ethyl-3-{[(4S)-4-hydroxy-4-methylisoxazolidin-2-yl]carbonyl}-5-methyl-2-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)thieno[2,3-d]pyridazin-4(5H)-one,
2-[(3,5-Dimethyl-1-(2-pyridinyl)-1H-pyrazol-4-yl)methyl]-3-[[(4S)-4-hydroxy-4-methyl-2-isoxazolidinyl]carbonyl-5-methyl-7-(1-methylethyl)thieno[2,3,-d]pyridazin-4(5H)-one,
2-[(3,5-Dimethyl-1-(2-pyrimidinyl)-1H-pyrazol-4-yl)methyl]-3-[[(4S)-4-hydroxy-4-methyl-2-isoxazolidinyl]carbonyl-5-methyl-7-(1-methylethyl)thieno[2,3,-d]pyridazin-4(5H)-one,
2-[(3,5-Dimethyl-1-(2-thiazolyl)-1H-pyrazol-4-yl)methyl]-3-[[(4S)-4-hydroxy-4-methyl-2-isoxazolidinyl]carbonyl-5-methyl-7-(1-methylethyl)thieno[2,3,-d]pyridazin-4(5H)-one.

14 more elements

A method of treating, or reducing the risk of, an airways disease in a patient suffering from, or at risk of, said disease, which comprises administering to the patient a therapeutically effective amount of a compound selected from the group consisting of

2-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-3-[[(4S)-4-hydroxy-2-isoxazolidinyl]carbonyl-5-methyl-7-(1-methylethyl)thieno[2,3,-d]pyridazin-4(5H)-one,
2-[(3,5-Dimethyl-1H-pyrazol-4-yl)methyl]-3-[[(4S)-4-hydroxy-2-isoxazolidinyl]carbonyl]-5-methyl-7-(2-methylpropyl)thieno[2,3-d]pyridazin-4(5H)-one,
2-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-7-ethyl-3-[[(4S)-4-hydroxy-2-isoxazolidinyl]carbonyl]-5-methyl-thieno[2,3-d]pyridazin-4(5H)-one,
7-Cycloprpyl-2[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-3-[[(4S)-4-hydroxy-2-isoxazolidinyl]carbonyl]-5-methyl-thieno[2,3-d]pyridazin-4(5H)-one,
7-Cyclopropyl-2-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-5-ethyl-3-[[(4S)-4-hydroxy-2-isoxazolidinyl]carbonyl]-thieno[2,3-d]pyridazin-4(5H)-one,
2-[(3,5-Dimethyl-1H-pyrazol-4-yl)methyl]-3-[[(4S)-4-methyl-2-isoxazolidinyl]carbonyl-5-methyl-7-(1-methylethyl)thieno[2,3,-d]pyridazin-4(5H)-one,
2-[(3,5-Dimethyl-1H-pyrazol-4-yl)methyl]-3-[[(4S)-4-hydroxy-4-methyl-2-isoxazolidinyl]carbonyl]-5-methyl-7-(2-methylpropyl)-thieno[2,3,-d]pyridazin-4(5H)-one,
2-[(3,5-Dimethyl-1H-pyrazol-40yl)methyl]-7-ethyl-3-[[(4S)-4-hydroxy-4-methyl-2-isoxazolidinyl]carbonyl]-5-methyl-thieno[2,3-d]pyridazin-4(5H)-one,
7-Cyclopropyl-2-[(3,5-dimethyl-1H-pyrazol-4-yl)methyl]-3-[[(4S)-4-hydroxy-4-methyl-2-isoxazolidinyl]carbonyl]-5-methyl-thieno[2,3-d]pyridazin-4(5H)-one,
3-[[(4S)-4-hydroxyisoxazolidinyl]carbonyl-5-methyl-7-(2-methylpropyl)-2-(1H-pyrrolo[2,3-b]pyridine-3-ylmethyl)thieno[2,3,-d]pyridazin-4(5H)-one,
3-[[(4S)-4-Hydroxy-2-isoxazolidinyl]carbonyl]-5-methyl-7-(2-methylpropyl)-2-[1,3,5-trimethylpyrazol-4-yl)methyl]-thieno[2,3,-d]pyridazin-4(5H)-one,
2-[[3,5-dimethyl-1-(2-pyridinyl)-1H-pyrazol-4-yl]methyl]-7-ethyl-3-[[(4S)-4-hydroxy-2-isoxazolidinyl]carbonyl]-5-methyl-thieno[2,3-d]pyridazin-4(5H)-one,
2-[[3,5-Dimethyl-1-(2-pyridinyl)-1H-pyrazol-4-yl]methyl]-7-ethyl-3-[[(4S)-4-hydroxy-4-methyl-2-isoxazolidinyl]carbonyl]-5-methyl-thieno[2,3-d]pyridazin-4(5H)-one,
7-Ethyl-3-{[(4S)-4-hydroxy-4-methylisoxazolidin-2-yl]carbonyl}-5-methyl-2-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)thieno[2,3-d]pyridazin-4(5H)-one,
2-[(3,5-Dimethyl-1-(2-pyridinyl)-1H-pyrazol-4-yl)methyl]-3-[[(4S)-4-hydroxy-4-methyl-2-isoxazolidinyl]carbonyl-5-methyl-7-(1-methylethyl)thieno[2,3,-d]pyridazin-4(5H)-one,
2-[(3,5-Dimethyl-1-(2-pyrimidinyl)-1H-pyrazol-4-yl)methyl]-3-[[(4S)-4-hydroxy-4-methyl-2-isoxazolidinyl]carbonyl-5-methyl-7-(1-methylethyl)thieno[2,3,-d]pyridazin-4(5H)-one,
2-[(3,5-Dimethyl-1-(2-thiazolyl)-1H-pyrazol-4-yl)methyl]-3-[[(4S)-4-hydroxy-4-methyl-2-isoxazolidinyl]carbonyl-5-methyl-7-(1-methylethyl)thieno[2,3,-d]pyridazin-4(5H)-one.

14 more elements

Dependencies are inferred from the claim text.

Facts

Application

11/447,343Filed 6 Jun 2006

Priority

SE 0300120-317 Jan 2003

Published

5 Oct 2006

Term ends

Not estimatedThe source records don’t support an estimate.

Classification32 codes

C07D 495/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents

Novel compounds

Life of this patent

Novel compounds

Life of this patent

Abstract

Claims5