US2003004193A1PendingUtilityA1

1-Heterocycle substituted diarylamines

46
Priority: Jan 13, 1999Filed: Jul 23, 2002Published: Jan 2, 2003
Est. expiryJan 13, 2019(expired)· nominal 20-yr term from priority
Inventors:Stephen Douglas BarrettAlexander James BridgesHaile TecleLu Zhang
A61P 37/02A61P 9/00A61P 9/08A61P 9/04A61P 9/10A61P 31/18A61P 3/10A61P 35/00A61P 31/12A61P 29/00A61P 25/28A61P 1/16A61P 19/02A61P 17/06C07D 249/14C07D 263/10C07D 231/46C07D 257/04C07D 291/04C07D 231/20C07D 285/08C07D 275/03C07D 249/06A61K 45/06C07D 271/07C07D 249/12
46
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Claims

Abstract

1-Heterocycle substituted diarylamines, methods of making and using them, and compositions containing them.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A compound of formula (I):  
       
         
           
           
               
               
           
         
       
       W is one of the following formulae (i)-(xiii):  
       
         
           
           
               
               
           
         
         X 1  is O, S, or NR F ;  
         X 2  is OH, SH, or NHR E ;  
         each of R E  and R F  is H or C 1-4  alkyl;  
         each of R 1  and R 2  is independently selected from H, F, NO 2 , Br and Cl; R 1  can also be SO 2 NR G R H , or R 1  and R 2  together with the benzene ring to which they are attached constitute an indole, isoindole, benzofuran, benzothiophene, indazole, benzimidazole, or benzthioazole;  
         R 3  is H or F;  
         each of R G , R H , and R 4  is independently selected from H, Cl and CH 3 ;  
         R 5  is H or C 3-4  alkyl; and  
         wherein each hydrocarbon radical above is optionally substituted with between 1 and 3 substituents independently selected from halo, hydroxyl, amino, (amino)sulfonyl, and NO 2 ; and  
         wherein each heterocyclic radical above is optionally substituted with between 1 and 3 substituents independently selected from halo, C 3-4  alkyl, C 3-6  cycloalkyl, C 3-4  alkenyl, C 3-4  alkynyl, phenyl, hydroxyl, amino, (amino)sulfonyl, and NO 2 , wherein each substituent alkyl, cycloalkyl, alkenyl, alkynyl or phenyl is in turn optionally substituted with between 1 and 2 substituents independently selected from halo, C 1-2  alkyl, hydroxyl, amino, and NO 2 ;  
         or a pharmaceutically acceptable salt or C 1-8  ester thereof.  
       
     
     
         2 . A compound of  claim 1 , wherein R 1  is bromo or chloro.  
     
     
         3 . A compound of  claim 1 , wherein R 2  is fluoro.  
     
     
         4 . A compound of  claim 1 , wherein R 3  is H.  
     
     
         5 . A compound of  claim 4 , wherein each of R 2  and R 3  is H.  
     
     
         6 . A compound of  claim 1 , wherein each of R 2  and R 3  is fluoro.  
     
     
         7 . A compound of  claim 6 , wherein R 1  is bromo.  
     
     
         8 . A compound of  claim 6 , wherein R 1  is fluoro.  
     
     
         9 . A compound of  claim 1 , wherein R 2  is nitro.  
     
     
         10 . A compound of  claim 8 , wherein R 3  is H.  
     
     
         11 . A compound of  claim 1 , wherein R 4  is chloro.  
     
     
         12 . A compound of  claim 1 , wherein R 4  is methyl.  
     
     
         13 . A compound of  claim 1 , wherein R 5  is H.  
     
     
         14 . A compound of  claim 1 , wherein R 5  is CH 3 .  
     
     
         15 . A compound of  claim 1 , wherein X 1  is O or S.  
     
     
         16 . A compound of  claim 1 , wherein X 1  is NH or NCH 3 .  
     
     
         17 . A compound of  claim 1 , wherein X 2  is OH, SH, or NH 2 .  
     
     
         18 . A compound of  claim 1 , wherein X 2  is NHCH 3  or OH.  
     
     
         19 . A pharmaceutical composition comprising a compound of  claim 1  and a pharmaceutically-acceptable carrier.  
     
     
         20 . A compound of  claim 1 , having a structure: [5-fluoro-2-(1H-tetrazol-5-yl)-phenyl]-(4-iodo-2-methyl-phenyl)-amine; [2,3-difluoro-6-(1H-tetrazol-5-yl)-phenyl]-(4-iodo-2-methyl-phenyl)-amine; (4-iodo-2-methyl-phenyl)-[2,3,4-trifluoro-6-(1H-tetrazol-5-yl)-phenyl]-amine; [4-bromo-2,3-difluoro-6-(1H-tetrazol -5-yl)-phenyl]-(4-iodo-2-methyl-phenyl)-amine; [5-fluoro4-nitro-2-(1H-tetrazol -5-yl)-phenyl]-(4-iodo-2-methyl-phenyl)-amine; [2-(4,4-dimethyl-4,5-dihydro-oxazol -2-yl)-5-fluoro-phenyl]-(4-iodo-2-methyl-phenyl)-amine; [6-(4,4-dimethyl -4,5-dihydro-oxazol-2-yl)-2,3-difluoro-phenyl]-(4-iodo-2-methyl-phenyl)-amine; [6-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-2,3,4-trifluoro-phenyl]-(4-iodo-2-methyl-phenyl)-amine; [4-bromo-6-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-2,3-difluoro-phenyl]-(4-iodo-2-methyl-phenyl)-amine; [2-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-5-fluoro -4-nitro-phenyl]-(4-iodo-2-methyl-phenyl)-amine; 5-[4-fluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-[1,3,4]thiadiazol-2-ol; 5-[3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-[1,3,4]thiadiazol-2-ol; 5-[3,4,5-trifluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-[1,3,4]thiadiazol-2-ol; 5-[5-bromo-3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-[1,3,4]thiadiazol-2-ol; 5-[4-fluoro-2-(4-iodo -2-methyl-phenylamino) -5-nitro-phenyl]-[1,3,4]thiadiazol-2-ol; 5-[4-fluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-[1,3,4]oxadiazol-2-ol; 5-[3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-[1,3,4]oxadiazol-2-ol; 5-[3,4,5-trifluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-[1,3,4]oxadiazol-2-ol; 5-[5-bromo-3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-[1,3,4]oxadiazol-2-ol; 5-[4-fluoro-2-(4-iodo -2-methyl-phenylamino) -5-nitro-phenyl]-[1,3,4]oxadiazol-2-ol; 5-[4-fluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-4H-[1,2,4]triazol-3-ol; 5-[3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-4H-[1,2,4]triazol-3-ol; 5-[3,4,5-trifluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-4H-[1,2,4]triazol-3-ol; 5-[5-bromo-3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]4H-[1,2,4]triazol-3-ol; or 5-[4-fluoro-2-(4-iodo -2-methyl-phenylamino)-5-nitro-phenyl]4H-[1,2,4]triazol-3-ol.  
     
     
         21 . A compound of  claim 1 , having a structure: 5-[4-fluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-[1,3,4]thiadiazol-2-ylamine; 5-[3,4-Difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-[1,3,4]thiadiazol -2-ylamine; 5-[3,4,5-Trifluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-[1,3,4]thiadiazol-2-ylamine; 5-[5-bromo-3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-[1,3,4]thiadiazol-2-ylamine; 5-[4-fluoro-2-(4-iodo -2-methyl-phenylamino) -5-nitro-phenyl]-[1,3,4]thiadiazol-2-ylamine; 5-[4-Fluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-[1,3,4]oxadiazol-2-ylamine; 5-[3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-[1,3,4]oxadiazol-2-ylamine; 5-[3,4,5-trifluoro -2-(4-iodo-2-methyl-phenylamino)-phenyl]-[1,3,4]oxadiazol-2-ylamine; 5-[5-bromo-3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-[1,3,4]oxadiazol-2-ylamine; 5-[4-fluoro-2-(4-iodo-2-methyl-phenylamino)-5-nitro-phenyl]-[1,3,4]oxadiazol -2-ylamine; 5-[4-fluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-4H-[1,2,4]triazol -3-ylamine; 5-[3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-4H-[1,2,4]triazol-3-ylamine; 5-[3,4,5-trifluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-4H-[1,2,4]triazol-3-ylamine; 5-[5-bromo-3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-4H-[1,2,4]triazol-3-ylamine; 5-[4-fluoro-2-(4-iodo -2-methyl-phenylamino) -5-nitro-phenyl]-4H-[1,2,4]triazol-3-ylamine; 5-[4-fluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-[1,3,4]thiadiazole-2-thiol; 5-[3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-[1,3,4]thiadiazole-2-thiol; 5-[3,4,5-trifluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-[1,3,4]thiadiazole-2-thiol; 5-[5-bromo -3,4-difluoro -2-(4-iodo-2-methyl-phenylamino)-phenyl]-[1,3,4]thiadiazole-2-thiol; 5-[4-fluoro -2-(4-iodo-2-methyl-phenylamino)-5-nitro-phenyl]-[1,3,4]thiadiazole-2-thiol; 5-[4-fluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-[1,3,4]oxadiazole-2-thiol; 5-[3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-[1,3,4]oxadiazole-2-thiol; 5-[3,4,5-trifluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-[1,3,4]oxadiazole-2-thiol; 5-[5-bromo-3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-[1,3,4]oxadiazole-2-thiol; 5-[4-fluoro-2-(4-iodo-2-methyl-phenylamino) -5-nitro-phenyl]-[1,3,4]oxadiazole-2-thiol; 5-[4-fluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]4H-[1,2,4]triazole-3-thiol; 5-[3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-4H-[1,2,4]triazole-3-thiol; 5-[3,4,5-trifluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]4H-[1,2,4]triazole-3-thiol; 5-[5-bromo-3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-4H-[1,2,4]triazole-3-thiol; or 5-[4-fluoro-2-(4-iodo -2-methyl-phenylamino)-5-nitro-phenyl]4H-[1,2,4]triazole-3-thiol.  
     
     
         22 . A compound of  claim 1 , having a structure: 5-[4-fluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-isothiazol-3-ol; 5-[3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-isothiazol -3-ol; 5-[3,4,5-trifluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-isothiazol -3-ol; 5-[5-bromo-3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-isothiazol -3-ol; 5-[4-fluoro-2-(4-iodo -2-methyl-phenylamino) -5-nitro-phenyl]-isothiazol-3-ol; 5-[4-fluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-isoxazol -3-ol; 5-[3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-isoxazol -3-ol; 5-[3,4,5-trifluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-isoxazol -3-ol; 5-[5-bromo-3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-isoxazol -3-ol; 5-[4-fluoro-2-(4-iodo -2-methyl-phenylamino) -5-nitro-phenyl]-isoxazol-3-ol; 5-[4-fluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-1H-pyrazol-3-ol; 5-[3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-1H-pyrazol-3-ol; 5-[3,4,5-trifluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-1H-pyrazol-3-ol; 5-[5-bromo-3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-1H-pyrazol-3-ol; 5-[4-fluoro-2-(4-iodo-2-methyl-phenylamino)-5-nitro-phenyl]-1H-pyrazol-3-ol; 4-[4-fluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-isothiazol-3-ol; 4-[3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-isothiazol-3-ol; 4-[3,4,5-trifluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-isothiazol-3-ol; 4-[5-bromo -3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-isothiazol-3-ol; 4-[4-fluoro-2-(4-iodo-2-methyl-phenylamino)-5-nitro-phenyl]-isothiazol-3-ol; 4-[4-fluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-isoxazol-3-ol; 4-[3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-isoxazol-3-ol; 4-[3,4,5-trifluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-isoxazol-3-ol; 4-[5-bromo-3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-isoxazol-3-ol; 4-[4-fluoro-2-(4-iodo-2-methyl-phenylamino) -5-nitro-phenyl]-isoxazol-3-ol; 4-[4-fluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-1-methyl-1H-pyrazol-3-ol; 4-[3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-1-methyl-1H-pyrazol-3-ol; 1-methyl4-[3,4,5-trifluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-1H-pyrazol-3-ol; 4-[5-bromo-3,4-difluoro -2-(4-iodo-2-methyl-phenylamino)-phenyl]-1-methyl-1H-pyrazol-3-ol; or 4-[4-fluoro -2-(4-iodo-2-methyl-phenylamino)-5-nitro-phenyl]-1-methyl-1H-pyrazol-3-ol.  
     
     
         23 . A compound of  claim 1 , having a structure: 5-[2-(2-amino-4-iodo-phenylamino) -4-fluoro-phenyl]-1-methyl-1H-[1,2,3]triazol-4-ol; 5-[2-(2-amino -4-iodo-phenylamino)-3,4-difluoro-phenyl]-1-methyl-1H-[1,2,3]triazol-4-ol; 5-[2-(2-amino-4-iodo-phenylamino)-3,4,5-trifluoro-phenyl]-1-methyl-1H-[1,2,3]triazol-4-ol; 5-[2-(2-amino-4-iodo-phenylamino)-5-bromo-3,4-difluoro-phenyl]-1-methyl-1H-[1,2,3]triazol-4-ol; 5-[2-(2-amino-4-iodo-phenylamino)-4-fluoro-5-nitro-phenyl]-1-methyl-1H-[1,2,3]triazol-4-ol; 5-[4-fluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-3-methyl-3H-[1,2,3]triazol-4-ol; 5-[3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-3-methyl-3H-[1,2,3]triazol4-ol; 3-methyl-5-[3,4,5-trifluoro -2-(4-iodo-2-methyl-phenylamino)-phenyl]-3H-[1,2,3]triazol-4-ol; 5-[5-bromo -3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-3-methyl-3H-[1,2,3]triazol-4-ol; 5-[4-fluoro-2-(4-iodo-2-methyl-phenylamino)-5-nitro-phenyl]-3-methyl-3H-[1,2,3]triazol-4-ol; 4-[4-fluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-2-methyl -2H-pyrazol-3-ol; 4-[3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-2-methyl-2H-pyrazol-3-ol; 2-methyl-4-[3,4,5-trifluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-2H-pyrazol-3-ol; 4-[5-bromo-3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-2-methyl-2H-pyrazol-3-ol; 4-[4-fluoro-2-(4-iodo -2-methyl-phenylamino)-5-nitro-phenyl]-2-methyl-2H-pyrazol-3-ol; 1-[4-fluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-4-methyl-1,4-dihydro-tetrazol-5-one; 1-[3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-4-methyl-1,4-dihydro-tetrazol -5-one; 1-methyl-4-[3,4,5-trifluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-1,4-dihydro-tetrazol-5-one; 1-[5-bromo-3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-4-methyl-1,4-dihydro-tetrazol-5-one; 1-[4-fluoro-2-(4-iodo-2-methyl-phenylamino) -5-nitro-phenyl]-4-methyl-1,4-dihydro-tetrazol-5-one; 1-[4-fluoro -2-(4-iodo-2-methyl-phenylamino)-phenyl]-1H-[1,2,3]triazol-4-ol; 1-[3,4-difluoro -2-(4-iodo -2-methyl-phenylamino)-phenyl]-1H-[1,2,3]triazol-4-ol; 1-[3,4,5-trifluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-1H-[1,2,3]triazol-4-ol; 1-[5-bromo -3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-1H-[1,2,3]triazol-4-ol; or 1-[4-fluoro-2-(4-iodo-2-methyl-phenylamino)-5-nitro-phenyl]-1H-[1,2,3]triazol-4-ol.  
     
     
         24 . A compound of  claim 1 , having a structure: 3-[4-fluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-2H-isoxazol-5-one; 3[3,4-difluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-2H-isoxazol-5-one; 3-[3,4,5-trifluoro-2-(4-iodo -2-methyl-phenylamino)-phenyl]-2H-isoxazol-5-one; 3-[5-bromo-3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-2H-isoxazol-5-one; 3-[4-fluoro-2-(4-iodo -2-methyl-phenylamino)-5-nitro-phenyl]-2H-isoxazol-5-one; [5-fluoro-2-(2-oxo -2,3-dihydro-2l>4_-[1,2,3,5]oxathiadiazol-4-yl)-phenyl]-(4-iodo -2-methyl-phenyl)-amine; [2,3-difluoro-6-(2-oxo-2,3-dihydro-2l>4_-[1,2,3,5]oxathiadiazol 4-yl)-phenyl]-(4-iodo-2-methyl-phenyl)-amine; (4-Iodo-2-methyl-phenyl)-[2,3,4-trifluoro -6-(2-oxo-2,3-dihydro-2l>4_-[1,2,3,5]oxathiadiazol-4-yl)-phenyl]-amine; [4-bromo -2,3-difluoro-6-(2-oxo-2,3-dihydro-2l>4_-[1,2,3,5]oxathiadiazol 4-yl)-phenyl]-(4-iodo -2-methyl-phenyl)-amine; [5-fluoro-4-nitro-2-(2-oxo-2,3-dihydro-2l>4_-[1,2,3,5]oxathiadiazol-4-yl)-phenyl]-(4-iodo-2-methyl-phenyl)-amine; 4-[4-fluoro -2-(4-iodo-2-methyl-phenylamino)-phenyl]-4H-isoxazol-5-one; 4-[3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-4H-isoxazol-5-one; 4-[3,4,5-trifluoro-2-(4-iodo-2-methyl-phenylamino)-phenyl]-4H-isoxazol-5-one; 4-[5-bromo-3,4-difluoro -2-(4-iodo-2-methyl-phenylamino)-phenyl]-4H-isoxazol-5-one; or 4-[4-fluoro-2-(4-iodo-2-methyl-phenylamino)-5-nitro-phenyl]-4H-isoxazol-5-one.  
     
     
         25 . A method for treating a proliferative disease, said method comprising administering to a patient in need of such treatment a pharmaceutically-effective amount of a composition comprising a compound of  claim 1 .  
     
     
         26 . A method of  claim 25 , wherein said proliferative disease is selected from psoriasis, restenosis, autoimmune disease, and atherosclerosis.  
     
     
         27 . A method for treating cancer, said method comprising administering to a patient in need of such treatment a pharmaceutically-effective amount of a composition comprising a compound of  claim 1 .  
     
     
         28 . A method of  claim 27 , wherein said cancer is MEK-related.  
     
     
         29 . A method of  claim 27 , wherein said cancer is brain, breast, lung, ovarian, pancreatic, prostate, renal, or colorectal cancer.  
     
     
         30 . A method for treating, or ameliorating the sequelae of, a stroke, said method comprising administering to a patient in need of such treatment a pharmaceutically-effective amount of a composition comprising a compound of  claim 1 .  
     
     
         31 . A method for treating, or ameliorating the sequelae of, heart failure, said method comprising administering to a patient in need of such treatment a pharmaceutically-effective amount of a composition comprising a compound of  claim 1 .  
     
     
         32 . A method for treating or reducing the symptoms of xenograft rejection, said method comprising administering to an organ transplant, limb transplant, skin transplant, cell(s) transplant, or bone marrow transplant patient a pharmaceutically-effective amount of a composition comprising a compound of  claim 1 .  
     
     
         33 . A method for treating osteoarthritis, said method comprising administering to a patient in need of such treatment a pharmaceutically-effective amount of a composition comprising a compound of  claim 1 .  
     
     
         34 . A method for treating rheumatoid arthritis, said method comprising administering to a patient in need of such treatment a pharmaceutically-effective amount of a composition comprising a compound of  claim 1 .  
     
     
         35 . A method for treating cystic fibrosis, said method comprising administering to a patient in need of such treatment a pharmaceutically-effective amount of a composition comprising a compound of  claim 1 .  
     
     
         36 . A method for treating hepatomegaly, said method comprising administering to a patient in need of such treatment a pharmaceutically-effective amount of a composition comprising a compound of  claim 1 .  
     
     
         37 . A method for treating cardiomegaly, said method comprising administering to a patient in need of such treatment a pharmaceutically-effective amount of a composition comprising a compound of  claim 1 .  
     
     
         38 . A method for treating Alzheimer's disease, said method comprising administering to a patient in need of such treatment a pharmaceutically-effective amount of a composition comprising a compound of  claim 1 .  
     
     
         39 . A method for treating a complication of diabetes, said method comprising administering to a patient in need of such treatment a pharmaceutically-effective amount of a composition comprising a compound of  claim 1 .  
     
     
         40 . A method for treating septic shock, said method comprising administering to a patient in need of such treatment a pharmaceutically-effective amount of a composition comprising a compound of  claim 1 .  
     
     
         41 . A method for treating a viral infection, said method comprising administering to a patient in need of such treatment a pharmaceutically-effective amount of a composition comprising a compound of  claim 1 .  
     
     
         42 . A method of  claim 41 , wherein said infection is an infection of HIV.  
     
     
         43 . A method for treating cancer, said method comprising (a) administering to a patient in need of such treatment, a pharmaceutically-effective amount of a composition comprising a compound of  claim 1;  and (b) administering a therapy selected from radiation therapy and chemotherapy.  
     
     
         44 . A method of  claim 43 , wherein said chemotherapy comprises a mitotic inhibitor.  
     
     
         45 . A method of  claim 44 , wherein said mitotic inhibitor is selected from paclitaxel, docetaxel, vincristine, vinblastine, vinorelbine, and vinflunine.

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