Inhibitors of raf kinases

Abstract

Provided herein are inhibitors of receptor tyrosine kinase effector, RAF, pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.

1 .- 54 . (canceled) 
     
     
         55 . A compound, or pharmaceutically acceptable salt or solvate thereof, selected from the group consisting of:
 (3S)-N-[4-methyl-3-[2-methyl-6-(morpholin-4-yl)pyridin-4-yl]phenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   4-[2-methyl-5-[(3S)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carbonylamino]phenyl]-6-(morpholin-4-yl)pyridine-2-carboxamide;   N-methyl-4-[2-methyl-5-[(3S)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carbonylamino]phenyl]-6-(morpholin-4-yl)pyridine-2-carboxamide;   N-(2-hydroxyethyl)-4-[2-methyl-5-[(3S)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carbonylamino]phenyl]-6-(morpholin-4-yl)pyridine-2-carboxamide;   N-[(2R)-2-hydroxypropyl]-4-[2-methyl-5-[(3S)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carbonylamino]phenyl]-6-(morpholin-4-yl)pyridine-2-carboxamide;   N-[(2R)-1-hydroxypropan-2-yl]-4-[2-methyl-5-[(3S)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carbonylamino]phenyl]-6-(morpholin-4-yl)pyridine-2-carboxamide;   N-[(2S)-2-hydroxypropyl]-4-[2-methyl-5-[(3S)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carbonylamino]phenyl]-6-(morpholin-4-yl)pyridine-2-carboxamide;   N-[(2S)-1-hydroxypropan-2-yl]-4-[2-methyl-5-[(3S)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carbonylamino]phenyl]-6-(morpholin-4-yl)pyridine-2-carboxamide;   N-(2-hydroxy-2-methylpropyl)-4-[2-methyl-5-[(3S)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carbonylamino]phenyl]-6-(morpholin-4-yl)pyridine-2-carboxamide;   (3S)-N-[3-[2-(3-hydroxy-3-methylbut-1-yn-1-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-(3-[2-[(3R)-3-hydroxybut-1-yn-1-yl]-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-(3-[2-[(3R)-3-hydroxybutyl]-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-(3-[2-[(1R,2S)-2-(hydroxymethyl)cyclopropyl]-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[4-methyl-3-[2-(1-methyl-1,2,3-triazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[4-methyl-3-[2-(morpholin-4-yl)-6-(1,3-thiazol-5-yl)pyridin-4-yl]phenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[4-methyl-3-[2-(3-methylimidazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-(3-[2-[(1E,3R)-3-hydroxybut-1-en-1-yl]-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   N-(2-hydroxyethyl)-N-methyl-4-[2-methyl-5-[(3S)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carbonylamino]phenyl]-6-(morpholin-4-yl)pyridine-2-carboxamide;   N, N-dimethyl-4-[2-methyl-5-[(3S)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carbonylamino]phenyl]-6-(morpholin-4-yl)pyridine-2-carboxamide;   (3S)-N-[3-[2-(3-hydroxyazetidine-1-carbonyl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2-(3-hydroxy-3-methylazetidine-1-carbonyl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[4-methyl-3-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-(3-[2-[(1E)-3-hydroxyprop-1-en-1-yl]-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2-(3-hydroxypropyl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2-methoxy-6-(morpholin-4-yl)-[2,4-bipyridin]-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2-(2-hydroxy-1,3-oxazol-5-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2-(2-hydroxypropan-2-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[4-methyl-3-[2-(morpholin-4-yl)-6-(piperidin-3-yl)pyridin-4-yl]phenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-(2-[[(2R)-2-hydroxypropyl](methyl)amino]-6-(morpholin-4-yl)pyridin-4-yl)-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2-hydroxy-6-(morpholin-4-yl)-[2,4-bipyridin]-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[4-methyl-3-[1′-methyl-6-(morpholin-4-yl)-3′,6′-dihydro-2′H-[2,4′-bipyridin]-4-yl]phenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2-(2-hydroxyethyl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[4-methyl-3-[2-(morpholin-4-yl)-6-(1H-pyrazol-4-yl)pyridin-4-yl]phenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-(4-methyl-3-(2-morpholino-6-(pyrrolidin-3-yl)pyridin-4-yl)phenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[4-methyl-3-[2-(1-methyl-2,5-dihydropyrrol-3-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[4-methyl-3-[2-(1-methylpyrazol-3-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2-(1,3-dimethylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-(4-methyl-3-(2-(1-methylpyrrolidin-3-yl)-6-morpholinopyridin-4-yl)phenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (S)-N-(4-methyl-3-(2-(1-methylpiperidin-4-yl)-6-morpholinopyridin-4-yl)phenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2′-amino-6-(morpholin-4-yl)-[2,4′-bipyridin]-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-(3-[2-[1-(difluoromethyl)pyrazol-4-yl]-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[4-methyl-3-[2-(morpholin-4-yl)-6-(1,3-thiazol-4-yl)pyridin-4-yl]phenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2-(2-amino-3H-imidazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2-(5-amino-1-methylpyrazol-3-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2-(2-aminopyrimidin-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2′-(difluoromethyl)-6-(morpholin-4-yl)-[2,4′-bipyridin]-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[4-methyl-3-[2-(3-methyl-1H-pyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2-(1,5-dimethylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[4-methyl-3-[2-(2-methylpyrazol-3-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2-(2,5-dimethylpyrazol-3-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2-(3,5-dimethyl-1H-pyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2-(1,5-dimethylpyrazol-3-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2-(1H-imidazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-{4-methyl-3-[2-(1-methylimidazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-{3-[2-(3-aminobut-1-yn-1-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl}-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[4-methyl-3-[2-(morpholin-4-yl)-6-(trifluoromethyl)pyridin-4-yl]phenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-{3-[2-(difluoromethyl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl}-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-(3-(2-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-(3-{2-[2-(2-hydroxyethyl)pyrazol-3-yl]-6-(morpholin-4-yl)pyridin-4-yl}-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-[3-[2-(hydroxymethyl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-{4-methyl-3-[2-(4-methyl-1,2,4-triazol-3-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (2S)-N-{4-methyl-3-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-2-(trifluoromethyl)morpholine-4-carboxamide;   (2R)-N-{4-methyl-3-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-2-(trifluoromethyl)morpholine-4-carboxamide;   (3R)-N-{4-methyl-3-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(trifluoromethoxy)pyrrolidine-1-carboxamide;   (2R)-N-{4-methyl-3-[2-(2-methylpyrazol-3-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-2-(trifluoromethyl)morpholine-4-carboxamide;   N-{4-methyl-3-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(trifluoromethyl)-2,5-dihydropyrrole-1-carboxamide;   (2S)-N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-2-(trifluoromethyl)morpholine-4-carboxamide;   (2R)-N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-2-(trifluoromethyl)morpholine-4-carboxamide;   N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(trifluoromethyl)-2,5-dihydropyrrole-1-carboxamide;   (3S)-N-{2-fluoro-4-methyl-5-[2-methyl-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-{5-[2-cyclopropyl-6-(morpholin-4-yl)pyridin-4-yl]-2-fluoro-4-methylphenyl}-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-{5-[2-ethyl-6-(morpholin-4-yl)pyridin-4-yl]-2-fluoro-4-methylphenyl}-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   N-{2-fluoro-4-methyl-5-[2-(2-methylpyrazol-3-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(trifluoromethyl)-2,5-dihydropyrrole-1-carboxamide;   (3S)-N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   (3R)-N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(trifluoromethyl)pyrrolidine-1-carboxamide;   (3S)-N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(trifluoromethyl)pyrrolidine-1-carboxamide;   N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(2,2,2-trifluoroethyl)-2,5-dihydropyrrole-1-carboxamide;   (3S)-N-{3-[2-(1-ethylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl}-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide;   N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(1,1,2,2,2-pentafluoroethyl)-2,5-dihydropyrrole-1-carboxamide;   (3R)-N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(1,1,2,2,2-pentafluoroethyl)pyrrolidine-1-carboxamide;   (3S)-N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(1,1,2,2,2-pentafluoroethyl)pyrrolidine-1-carboxamide;   (3S)-3-tert-butyl-N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}pyrrolidine-1-carboxamide;   (3R)-3-tert-butyl-N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}pyrrolidine-1-carboxamide;   (3R)-3-(1,1-difluoroethyl)-N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}pyrrolidine-1-carboxamide; and   N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(2-fluoropropan-2-yl)pyrrolidine-1-carboxamide.   
     
     
         56 . The compound, or pharmaceutically acceptable salt or solvate thereof, of  claim 55  having the structure of:
 (3S)-N-[3-[2-(1H-imidazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide. 
 
     
     
         57 . The compound, or pharmaceutically acceptable salt or solvate thereof, of  claim 55  having the structure of:
 N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(trifluoromethyl)-2,5-dihydropyrrole-1-carboxamide. 
 
     
     
         58 . The compound, or pharmaceutically acceptable salt or solvate thereof, of  claim 55  having the structure of:
 (3S)-N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide. 
 
     
     
         59 . The compound, or pharmaceutically acceptable salt or solvate thereof, of  claim 55  having the structure of:
 N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(2,2,2-trifluoroethyl)-2,5-dihydropyrrole-1-carboxamide. 
 
     
     
         60 . The compound, or pharmaceutically acceptable salt or solvate thereof, of  claim 55  having the structure of:
 N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(2-fluoropropan-2-yl)pyrrolidine-1-carboxamide. 
 
     
     
         61 . A pharmaceutical composition comprising a compound, or pharmaceutically acceptable salt or solvate thereof, as described in  claim 55  and a pharmaceutically acceptable excipient. 
     
     
         62 . The pharmaceutical composition comprising a compound, or pharmaceutically acceptable salt or solvate thereof, as described in  claim 61  and a pharmaceutically acceptable excipient, wherein the compound is (3S)-N-[3-[2-(1H-imidazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]-4-methylphenyl]-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide. 
     
     
         63 . The pharmaceutical composition comprising a compound, or pharmaceutically acceptable salt or solvate thereof, as described in  claim 61  and a pharmaceutically acceptable excipient, wherein the compound is N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(trifluoromethyl)-2,5-dihydropyrrole-1-carboxamide 
     
     
         64 . The pharmaceutical composition comprising a compound, or pharmaceutically acceptable salt or solvate thereof, as described in  claim 61  and a pharmaceutically acceptable excipient, wherein the compound is (3S)-N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide. 
     
     
         65 . The pharmaceutical composition comprising a compound, or pharmaceutically acceptable salt or solvate thereof, as described in  claim 61  and a pharmaceutically acceptable excipient, wherein the compound is N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(2,2,2-trifluoroethyl)-2,5-dihydropyrrole-1-carboxamide. 
     
     
         66 . The pharmaceutical composition comprising a compound, or pharmaceutically acceptable salt or solvate thereof, as described in  claim 61  and a pharmaceutically acceptable excipient, wherein the compound is N-{2-fluoro-4-methyl-5-[2-(1-methylpyrazol-4-yl)-6-(morpholin-4-yl)pyridin-4-yl]phenyl}-3-(2-fluoropropan-2-yl)pyrrolidine-1-carboxamide.