Amino-thio-acrylonitriles as MEK inhibitors

Abstract

This invention relates generally to amino-thio-acrylonitriles of formula Ia or Ib: as MEK inhibitors, pharmaceutical compositions containing the same, and methods of using the same as for treatment and prevention of inflammatory disorders or as an anticancer radiosensitizing agent.

What is claimed is:  
     
         1 . A compound of formula Ia or Ib:  
       
         
           
           
               
               
           
         
         or stereoisomer or pharmaceutically acceptable salt form thereof, wherein;  
         R 1  is phenyl, naphthyl, 2,3-dihydroindol-5-yl or a 5-6 membered heteroaryl ring with 1-4 heteroatoms selected from N, NH, O, and S, and R 1  is substituted with 0-2 R a ;  
         R a  is selected from H, Cl, F, Br, I, C 1-4  alkyl, C 1-4  alkoxy, OH, CH 2 OH, NH 2 , (C 1-3  alkyl)NH, (C 1-3  alkyl) 2 N, (H 2 NCH 2 C(O))NH, (H 2 NCH(CH 3 )C(O))NH, (CH 3 NHCH 2 C(O))NH, ((CH 3 ) 2 NCH 2 C(O))NH, CF 3 , OCF 3 , CN, NO 2 , C(O)NH 2 , and CH 3 C(O)NH;  
         Y is selected from phenyl substituted with 0-5 R b , naphthyl substituted with 0-5 R b , and CHR 3 ;  
         R b  is selected from H, Cl, F, Br, I, C 1-4  alkyl, OH, C 1-4  alkoxy, CH 2 OH, CH(OH)CH 3 , CF 3 , OCF 3 , —CN, NO 2 , NH 2 , (C 1-3  alkyl)NH, (C 1-3  alkyl) 2 N, and C(O)O—C 1-4  alkoxy;  
         R 2  is selected from H, R 2a , C(O)R 2a , CH(OH)R 2a , CH 2 R 2a , OR 2a , SR 2a , and NHR 2a ;  
         R 2a  is selected from phenyl, naphthyl, and a 5-6 membered heteroaryl ring with 1-4 heteroatoms selected from N, NH, O, and S, and R 2a  is substituted with 0-5 R b ;  
         R 3  is phenyl substituted with 0-2 R c  or naphthyl substituted with 0-2 R c ; and,  
         R c  is selected from H, Cl, F, Br, I, C 1-4  alkyl, OH, C 1-4  alkoxy, CH 2 OH, CH(OH)CH 3 , CF 3 , OCF 3 , —CN, NO 2 , NH 2 , (C 1-3  alkyl)NH, (C 1-3  alkyl) 2 N, and C(O)O-C 1-4  alkoxy.  
       
     
     
         2 . A compound of  claim 1 , wherein: 
 R 1  is phenyl or a 5-6 membered heteroaryl ring with 1-2 heteroatoms selected from N, NH, O, and S, and R 1  is substituted with 0-2 Ra;    R a  is selected from H, Cl, F, C 1-4  alkyl, C 1-4  alkoxy, OH, CH 2 OH, NH 2 , (C 1-3  alkyl)NH, (C 1-3  alkyl) 2 N, (H 2 NCH 2 C(O))NH, (H 2 NCH(CH 3 )C(O))NH, (CH 3 NHCH 2 C(O))NH, ((CH 3 ) 2 NCH 2 C(O))NH, and CH 3 C(O)NH;    Y is selected from phenyl substituted with 0-5 R b , naphthyl substituted with 0-5 R b , and CHR 3 ;    R b  is selected from H, Cl, F, Br, C 1-4  alkyl, OH, C 1-4  alkoxy, CH 2 OH, CH(OH)CH 3 , CF 3 , —CN, NO 2 , NH 2 , and (C 1-3  alkyl)NH, (C 1-3  alkyl) 2 N;    R 2  is selected from H, R 2a , C(O)R 2a , CH(OH)R 2a , CH 2 R 2a , and OR 2a ;    R 2a  is selected from phenyl, naphthyl, and a 5-6 membered heteroaryl ring with 1-4 heteroatoms selected from N, NH, O, and S, and R 2a  is substituted with 0-5 R b ;    R 3  is phenyl substituted with 0-2 R c  or naphthyl substituted with 0-2 R c ; and,    R c  is selected from H, Cl, F, Br, I, C 1-4  alkyl, OH, C 1-4  alkoxy, CH 2 OH, CH(OH)CH 3 , CF 3 , —CN, NO 2 , NH 2 , (C 1-3  alkyl)NH, and (C 1-3  alkyl) 2 N.    
     
     
         3 . A compound according to  claim 2 , wherein: 
 R 1  is phenyl or a 5-6 membered heteroaryl ring with 1-2 heteroatoms selected from N, NH, O, and S, and R 1  is substituted with 0-2 R a ;    R a  is selected from H, OH, and NH 2 ;    Y is selected from phenyl substituted with 0-2 R b , naphthyl substituted with 0-2 R b , and CHR 3 ;    R b  is selected from H, Cl, F, Br, C 1-4  alkyl, OH, C 1-4  alkoxy, CH 2 OH, CH(OH)CH 3 , CF 3 , —CN, NO 2 , NH 2 , and (C 1-3  alkyl)NH, (C 1-3  alkyl) 2 N;    R 2  is selected from H, R 2a , C(O)R 2a , CH(OH)R 2a , CH 2 R 2a , and OR 2a ;    R 2a  is selected from phenyl, naphthyl, and a 5-6 membered heteroaryl ring with 1-4 heteroatoms selected from N, NH, O, and S, and R 2a  is substituted with 0-5 R b ;    R 3  is phenyl substituted with 0-2 R c  or naphthyl substituted with 0-2 R c ; and,    R c  is selected from H, Cl, F, Br, I, C 1-4  alkyl, OH, C 1-4  alkoxy, CH 2 OH, CH(OH)CH 3,  CF 3 , —CN, NO 2 , NH 2 , (C 1-3  alkyl)NH, and (C 1-3  alkyl) 2 N.    
     
     
         4 . A compound according to  claim 1 , wherein the compound is selected from: 
 E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-4-chloro-2-methyl-β-phenylbenzenepropanenitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(2,4-dinitrophenyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(4-carbomethoxyphenyl)hydroxymethyl]benzeneacetonitrile    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(4-nitrophenyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(pentafluorophenyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-2-methyl-3-[(4-;yridyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-2-methyl-3-[(phenyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-2-methyl-3-[4-pyridyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(2-hydroxyphenyl)thio]methylene]-3-[(4-cyanophenyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(3nitrophenyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-2methyl-3-[(pentafluorophenyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(2-hydroxyphenyl)thio]methylene]-3-[(4-pyridyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(2-trifluoromethylphenyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(4-aminophenyl)thio]methylene]-3-[(4-pyridyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(4-hydroxyphenyl)thio]methylene]-3-[(4-pyridyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(3-cyanophenyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(4-aminophenyl)thio]methylene]-3-[(4-cyanophenyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino(phenylthio)methylene]-3-[(4-cyanophenyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino(phenylthio)methylene]-3-[(4-pyridyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(4-aminophenyl)thio]methylene]-2-bromobenzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(2,4-dimethylphenyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(phenyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(2-thienyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-4-chloro-β-phenylbenzenepropanenitrile;    E- and Z-α-[amino[(2-thienyl)thio]methylene]-3-[(phenyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(2,4-diaminophenyl)thio]methylene]-1-naphthyleneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-2-methyl-β-(4-pyridyl)benzenepropanenitrile;    E- and Z-α-[amino[(4-aminophenyl)thio]methylene]-3-(benzyl)benzeneacetonitrile;    E- and Z-α-[amino[(2-naphthyl)thio]methylene]-1-naphthyleneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-3-(benzoyl)benzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-β-(1-methyl-2-pyrrolyl)benzenepropanenitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-3-phenoxybenzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-2-bromobenzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(2-furanyl)hydroxymethyl]benzeneacetonitrile;    E- and z-α-[amino[(2-thienyl)thio]methylene]-3-[(2,3,4,5,6-pentafluorophenyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(3-methyl-2-pyridyl)hydroxymethyl]benzeneacetonitrile;    E- and Z-α-[amino[(4-aminophenyl)thio]methylene]-2-methylbenzeneacetonitrile;    E- and Z-α-[amino[(4-aminophenyl)thio]methylene]-4-(1,1-dimethylethyl)benzeneacetonitrile;    E- and Z-α-[amino[(4-aminophenyl)thio]methylene]-1-naphthyleneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-3-(trifluoromethyl)benzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-1-naphthyleneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-2-(trifluoromethyl)benzeneacetonitrile;    E- and Z-α-[amino[(4-aminophenyl)thio]methylene]-4-methylbenzeneacetonitrile;    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-2-methylbenzeneacetonitrile;    E- and Z-α-[amino[(2-fluorophenyl)thio]methylene]-1-naphthyleneacetonitrile; and,    E- and Z-α-[amino[(2-aminophenyl)thio]methylene]-3-phenyl benzeneacetonitrile;    or a pharmaceutically acceptable salt form thereof.    
     
     
         5 . A compound according to  claim 1 , wherein the compound is selected from: 
 E-α-[amino[(2-aminophenyl)thio]methylene]-4-chloro-2-methyl-β-phenylbenzenepropanenitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-3-[(2,4-dinitrophenyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-3-[(4-carbomethoxyphenyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-3-[(4-nitrophenyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-3-[(pentafluorophenyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-2-methyl-3-[(4-pyridyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-2-methyl-3-[(phenyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-2-methyl-3-[(4-pyridyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(2-hydroxyphenyl)thio]methylene]-3-[(4-cyanophenyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-3-[(3-nitrophenyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-2-methyl-3-[(pentafluorophenyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(2-hydroxyphenyl)thio]methylene]-3-[(4-pyridyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-3-[(2-trifluoromethylphenyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(4-aminophenyl)thio]methylene]-3-[(4-pyridyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(4-hydroxyphenyl)thio]methylene]-3-[(4-pyridyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-3-[(3-cyanophenyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(4-aminophenyl)thio]methylene]-3-[(4-cyanophenyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino(phenylthio)methylene]-3-[(4-cyanophenyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino(phenylthio)methylene]-3-[(4-pyridyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(4-aminophenyl)thio]methylene]-2-bromobenzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-3-[(2,4-dimethylphenyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-3-[(phenyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-3-[(2-thienyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-4-chloro-β-phenylbenzenepropanenitrile;    E-α-[amino[(2-thienyl)thio]methylene]-3-[(phenyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(2,4-diaminophenyl)thio]methylene]-1-naphthyleneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-2-methyl-β-(4-pyridyl)benzenepropanenitrile;    E-α-[amino[(4-aminophenyl)thio]methylene]-3-(benzyl)benzeneacetonitrile;    E-α-[amino[(2-naphthyl)thio]methylene]-1-naphthyleneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-3-(benzoyl)benzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-β-(1-methyl-2-pyrrolyl)benzenepropanenitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-3-phenoxybenzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-2-bromobenzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-3-[(2-furanyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(2-thienyl)thio]methylene]-3-[(2,3,4,5,6pentafluorophenyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-3-[(3-methyl-2-pyridyl)hydroxymethyl]benzeneacetonitrile;    E-α-[amino[(4-aminophenyl)thio]methylene]-2-methylbenzeneacetonitrile;    E-α-[amino[(4-aminophenyl)thio]methylene]-4-(1,1-dimethylethyl)benzeneacetonitrile;    E-α-[amino[(4-aminophenyl)thio]methylene]-1-naphthyleneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-3-(trifluoromethyl)benzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-1-naphthyleneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-2-(trifluoromethyl)benzeneacetonitrile;    E-α-[amino[(4-aminophenyl)thio]methylene]-4-methylbenzeneacetonitrile;    E-α-[amino[(2-aminophenyl)thio]methylene]-2-methylbenzeneacetonitrile;    E-α-[amino[(2-fluorophenyl)thio]methylene]-1-naphthyleneacetonitrile; and,    E-α-[amino[(2-aminophenyl)thio]methylene]-3-phenyl benzeneacetonitrile; or a pharmaceutically acceptable salt form thereof.    
     
     
         6 . A compound according to  claim 1 , wherein the compound is selected from: 
 Z-α-[amino[(2-aminophenyl)thio]methylene]-4-chloro-2-methyl-β-phenylbenzenepropanenitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(2,4-dinitrophenyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(4-carbomethoxyphenyl)hydroxymethyl]benzeneacetonitrile    Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(4-nitrophenyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(pentafluorophenyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-2-methyl-3-[(4-pyridyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-2-methyl-3-[(phenyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-2-methyl-3-[(4-pyridyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(2-hydroxyphenyl)thio]methylene]-3-[(4-cyanophenyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(3-nitrophenyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-2-methyl-3-[(pentafluorophenyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(2-hydroxyphenyl)thio]methylene]-3-[(4-pyridyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(2-trifluoromethylphenyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(4-aminophenyl)thio]methylene]-3-[(4-pyridyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(4-hydroxyphenyl)thio]methylene]-3-[(4-pyridyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(3-cyanophenyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(4-aminophenyl)thio]methylene]-3-[(4-cyanophenyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino(phenylthio)methylene]-3-[(4-cyanophenyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino(phenylthio)methylene]-3-[(4-pyridyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(4-aminophenyl)thio]methylene]-2-bromobenzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(2,4-dimethylphenyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(phenyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(2-thienyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-4-chloro-β-phenylbenzenepropanenitrile;    Z-α-[amino[(2-thienyl)thio]methylene]-3-[(phenyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(2,4-diaminophenyl)thio]methylene]-1-naphthyleneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-2-methyl-β-(4-pyridyl)benzenepropanenitrile;    Z-α-[amino[(4-aminophenyl)thio]methylene]3-(benzyl)benzeneacetonitrile;    Z-α-[amino[(2-naphthyl)thio]methylene]-1-naphthyleneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-3-(benzoyl)benzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-β-(1-methyl-2-pyrrolyl)benzenepropanenitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-3-phenoxybenzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-2-bromobenzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(2-furanyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(2-thienyl)thio]methylene]-3-[(2,3,4,5,6-pentafluorophenyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-3-[(3-methyl-2-pyridyl)hydroxymethyl]benzeneacetonitrile;    Z-α-[amino[(4-aminophenyl)thio]methylene]-2-methylbenzeneacetonitrile;    Z-α-[amino[(4-aminophenyl)thio]methylene]-4-(1,1-dimethylethyl)benzeneacetonitrile;    Z-α-[amino[(4-aminophenyl)thio]methylene]-1-naphthyleneacetonitrile;.    Z-α-[amino[(2-aminophenyl)thio]methylene]-3-(trifluoromethyl)benzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-1-naphthyleneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-2-(trifluoromethyl)benzeneacetonitrile;    Z-α-[amino[(4-aminophenyl)thio]methylene]-4-methylbenzeneacetonitrile;    Z-α-[amino[(2-aminophenyl)thio]methylene]-2-methylbenzeneacetonitrile;    Z-α-[amino[(2-fluorophenyl)thio]methylene]-1-naphthyleneacetonitrile; and,    Z-α-[amino[(2-aminophenyl)thio]methylene]-3-phenyl benzeneacetonitrile;    or a pharmaceutically acceptable salt form thereof.    
     
     
         7 . A pharmaceutical composition, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of  claim 1  or a pharmaceutically acceptable salt form thereof.  
     
     
         8 . A method for treating or preventing a disorder related to MEK, comprising: administering to a patient in need thereof a therapeutically effective amount of a compound of  claim 1  or a pharmaceutically acceptable salt form thereof.  
     
     
         9 . A method of treating a condition or disease wherein the disease or condition is referred to as theumatoid arthritis, osteoarthritis, periodontitis, gingivitis, corneal ulceration, solid tumor growth and tumor invasion by secondary metastases, neovascular glaucoma, multiple sclerosis, or psoriasis in a mammal, comprising: administering to the mammal in need of such treatment a therapeutically effective amount of a compound of  claim 1  or a pharmaceutically acceptable salt form thereof.  
     
     
         10 . A method of treating a condition or disease wherein the disease or condition is referred to as fever, cardiovascular effects, hemorrhage, coagulation, cachexia, anorexia, alcoholism, acute phase response, acute infection, shock, graft versus host reaction, autoimmune disease or HIV infection in a mammal comprising administering to the mammal in need of such treatment a therapeutically effective amount of a compound of  claim 1  or a pharmaceutically acceptable salt form thereof.