Substituted arylamine derivatives and methods of use

Abstract

Selected compounds are effective for prophylaxis and treatment of diseases, such as angiogenesis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

1 . Compound of Formula IV  
       
         
           
           
               
               
           
         
       
       wherein R 2  is selected from unsubstituted or substituted phenyl, and 
 9-10 membered bicyclic and 11-14 membered tricyclic unsaturated or partially unsaturated heterocyclyl,  
 wherein substituted R 2  is optionally substituted with one or more substituents selected from halo, C 1-6 -alkyl, optionally substituted C 3-6 -cycloalkyl, optionally substituted phenyl, optionally substituted phenyl-C 1-C   4 -alkylenyl, C 1-2 -haloalkoxy, optionally substituted phenyloxy, optionally substituted 4-6 membered heterocyclyl-C 1 -C 6 -alkyl, optionally substituted 4-6 membered heterocyclyl-C 2 -C 4 -alkenyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyloxy, optionally substituted 4-6 membered heterocyclyl-C 1-4 -alkoxy, optionally substituted 4-6 membered heterocyclylsulfonyl, optionally substituted 4-6 membered heterocyclylamino, optionally substituted 4-6 membered heterocyclylcarbonyl, optionally substituted 4-6 membered heterocyclyl-C 1-4 -alkylcarbonyl, optionally substituted 4-6 membered heterocyclylcarbonyl-C 1-4 -alkyl, optionally substituted 4-6 membered heterocyclyl-C 1-4 -alkylcarbonylamino, optionally substituted 4-6 membered heterocyclyl-oxycarbonylamino, C 1-2 -haloalkyl, C 1-4 -aminoalkyl, nitro, amino, C 1-3 -alkylsulfonylamino, hydroxy, cyano, aminosulfonyl, C 1-2 -alkylsulfonyl, halosulfonyl, C 1-4 -alkylcarbonyl, amino-C 1-4 -alkylcarbonyl, alkylcarbonyl, C 1-3 -alkylamino-C 1-4 -alkylcarbonyl, C 1-3 -alkylamino-C 1-4 -alkylcarbonylamino, C 1-4 -alkoxycarbonyl-C 1-4 -alkyl, C 1-3 -alkylamino-C 1-3 -alkyl, C 1-3 -alkylamino-C 1-3 -alkoxy, C 1-3 -alkylamino-C 1-3 -alkoxy-C 1-3 -alkoxy, C 1-4 -alkoxycarbonyl, C 1-4 -alkoxycarbonylamino-C 1-4 -alkyl, C 1-3 -alkylsulfonylamino-C 1-3 -alkoxy, C 1-4 -hydroxyalkyl,  
                     
 and C 1-4 -alkoxy;  
 wherein R e  and R f  are independently selected from H and C 1-2 -haloalkyl;  
 wherein R g  is selected from H, C 1-3 -alkyl, optionally substituted phenyl-C 1-3 -alkyl, 4-6 membered heterocyclyl, and optionally substituted 4-6 membered heterocyclyl-C 1 -C 3 -alkyl, C 1-3 -alkoxy-C 1-2 -alkyl and C 1-3 -alkoxy-C 1-3 -alkoxy-C 1-3 -alkyl; and  
 wherein R 8  is one or more substituents independently selected from halo, amino, nitro, hydroxy, C 1-6 -alkyl, C 1-6 -haloalkyl, C 1-6 -alkoxy, C 1-6 -haloalkoxy, C 1-6 -aminoalkyl, C 1-6 -hydroxyalkyl, optionally substituted phenyl, optionally substituted heterocyclyl, optionally substituted heterocyclyl-C 1-6 -alkoxy, aminosulfonyl, C 3-6 -cycloalkyl, C 1-6 -alkylamino, C 1-6 -alkylamino-C 1-6 -alkyl, optionally substituted heterocyclyl-C 1-6 -alkylamino, optionally substituted heterocyclyl-C 1-6 -alkyl, C 1-6 -alkylamino-C 2-4 -alkynyl, C 1-6 -alkylamino-C 1-6 -alkoxy, C 1-6 -alkylamino-C 1-6 -alkoxy-C 1-6 -alkoxy, and optionally substituted heterocyclyl-C 2-4 -alkynyl;  
 and a pharmaceutically acceptable salt thereof;  
 provided R 2  is not 3-trifluoromethylphenyl when R 8  is 4-hydroxy or 3-hydroxy.  
 
     
     
         2 - 20 . (canceled)  
     
     
         21  A compound selected from: 
 6-amino-2,2-dimethyl-4H-benzo[1,4]oxazin-3-one;    3-(4-Boc-piperazin-1-ylmethyl)-5-trifluoromethyl-phenylamine;    3-(4-methyl-piperazin-1-ylmethyl)-4-pentafluoroethyl-phenylamine;    (3-amino-5-trifluoromethyl-phenyl)-(4-Boc-piperazin-1-yl)-methanone;    7-amino-2-(4-methoxybenzyl)-4,4-dimethyl-3,4-dihydro-2H-isoquinolin-1-one;    1-(7-amino-4,4-dimethyl-3,4-dihydro-1H-isoquinolin-2-yl)-ethanone;    4-tert-butyl-3-(1-Boc-pyrrolidin-3-ylmethoxy)-phenylamine;    4-tert-butyl-3-(1-Boc-azetidin-3-ylmethoxy)-phenylamine;    3,3-dimethyl-1-(1-methyl-piperidin-4-yl)-2,3-dihydro-1H-indol-6-ylamine;    {3-[3-amino-5-(trifluoromethyl)phenyl]propynyl}dimethylamine;    5-(1-methyl-(1,2,5,6-tetrahydropyrid-4-yl))-3-(trifluoro-methyl)phenylamine;    3,9,9-trimethyl-2,3,4,4a,9,9a-hexahydro-1H-3-aza-fluoren-6-ylamine;    3-(3-amino-5-trifluoromethyl-phenoxymethyl)-azetidine-1-carboxylic acid benzyl ester;    1-(1-methyl-4-piperidyl)indoline-6-ylamine;    1-acetyl-6-amino-3,3-dimethylindoline;    2-methyl-5-[1-methyl-1-(4-aminophenyl)-ethyl]-[1,3,4]oxadiazole;    4,4-dimethyl-1,2,3,4-tetrahydro-quinolin-7-ylamine;    1-ethyl-4,4-dimethyl-1,2,3,4-tetrahydro-quinolin-7-ylamine;    4-methyl-6-[2-(1-methylpyrrolidin-2-yl)-ethyl]-pyrimidin-2-ylamine; and    4-(1,1-dimethyl-2-pyrrolidin-1-yl-ethyl-phenylamine.    
     
     
         22 . A compound selected from: 
 1-[2-(2-tert-butyl-5-nitrophenoxy)-ethyl]-piperidine;    3,3-dimethyl-1-(1-methylpiperidin-4-ylmethyl)-6-nitro-2,3-dihydro-1H-indole;    1-(4,4-dimethyl-7-nitro-3,4-dihydro-1H-isoquinolin-2-yl)-ethanone;    4,4-dimethyl-7-nitro-1,2,3,4-tetrahydro-isoquinoline;    3,3-Dimethyl-1-(1-Boc-piperidin-4-ylmethyl)-6-nitro-2,3-dihydro-1H-indole;    1-[2-(tert-butyl)-5-nitrophenyl]-4-methylpiperazine;    1-(3,3-dimethyl-6-nitro-2,3-dihydro-indol-1-yl)ethanone;    2-methyl-5-[1-methyl-1-(4-nitrophenyl)-ethyl]-[1,3,4]oxadiazole;    5-[1-methyl-1-(4-nitrophenyl)-ethyl]-1H-pyrazole;    4-[1-methyl-1-(4-nitrophenyl)-ethyl]-pyrimidine;    4,4-dimethyl-7-nitro-1,2,3,4-tetrahydro-quinoline;    1-ethyl-4,4-dimethyl-7-nitro-1,2,3,4-tetrahydro-quinoline;    7-nitro-4-spiro-1′-cyclopropane-1,2,3,4-tetrahydroisoquinoline; and    3-(2-chloro-5-nitro-phenoxymethyl)-azetidine-1-carboxylic acid tert-butyl ester.