Novel compounds

Abstract

The invention relates to thienopyridazinones of formula (I): wherein: R 1 is C 1-6 alkyl, C 2-6 alkenyl or C 3-6 cycloalkyl which is optionally substituted by C 1-6 alkyl, each of the above being optionally substituted by one or more halogen atoms; R 2 is C 1-6 alkyl; R 3 is a group CO-G or SO 2 -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 C 1-4 alkyl; Q is CR 5 R 6 where R 5 and R 6 are as defined in the specification; and R 4 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.

1 - 15 . (canceled)  
     
     
         16 . 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.    
     
     
         17 . The method of  claim 16 , wherein the method includes treatment of allograft rejection.  
     
     
         18 . 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.    
     
     
         19 . The method of  claim 18 , wherein the airways disease is asthma or COPD.