Tricyclic protein kinase inhibitors

Abstract

This invention provides compounds of formula 1, having the structure which are useful as inhibitors of protein tyrosine kinase and are antiproliferative agents.

1 . A compound of formula 1 having the structure:  
     
       
         
         
             
             
         
       
     
     wherein: 
 Ar is cycloalkyl of 3 to 7 carbon atoms, which may be optionally substituted with one or more alkyl of 1 to 6 carbon atoms; or  
 Ar is a pyridinyl, pyrimidinyl, or phenyl ring; wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally mono-, di-, or tri-substituted with substituent(s) independently selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, benzoyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalkyl of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 3-9 carbon atoms, N,N-dialkylaminoalkoxy of 4-10 carbon atoms, mercapto, methylmercapto and benzoylamino; or  
 Ar is a bicyclic aryl or bicyclic heteroaryl ring system of 8 to 12 atoms where the bicyclic heteroaryl ring may contain 1 to 4 heteroatoms selected from N, O, and S wherein the bicyclic aryl or bicyclic heteroaryl ring may be optionally mono-di-, tri, or tetra-substituted with substituent(s) independently selected from the group consisting of halogen, oxo, thiocarbonyl, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalkyl of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 3-9 carbon atoms, N,N-dialkylaminoalkoxy of 4-10 carbon atoms, mercapto, methylmercapto, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, and benzoylamino; or  
 Ar is the radical:  
                     
 A′ is a pyridinyl, pyrimidinyl, or phenyl ring; wherein the pyridinyl, pyrimidinyl, or phenyl ring may be optionally mono- or di-substituted with a substituent(s) independently selected from the group consisting of alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halogen, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalkyl of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 3-9 carbon atoms, N,N-dialkylaminoalkoxy of 4-10 carbon atoms, mercapto, methylmercapto, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, and benzoylamino;  
 T is substituted on A′ at carbon and is —NH(CH 2 ) m —, —O(CH 2 ) m —, —S(CH 2 ) m —, —NR(CH 2 ) m —, —(CH 2 ) m —, —(CH 2 ) m NH—, —(CH 2 ) m O—, —(CH 2 ) m S—, —SO(CH 2 ) m —, —SO 2 (CH 2 ) m —, —CO(CH 2 ) m —, —(CH 2 ) m CO—, —(CH 2 ) m SO—, —(CH 2 ) m SO 2 — or —(CH 2 ) m NR—;  
 L is a phenyl ring that is optionally substituted with one, two, or three substituent(s) independently selected from the group consisting of alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halogen, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalkyl of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 3-9 carbon atoms, N,N-dialkylaminoalkoxy of 4-10 carbon atoms, mercapto, methylmercapto, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, and benzoylamino; or  
 L is a 5- or 6-membered heteroaryl ring where the heteroaryl ring contains 1 to 3 heteroatoms selected from N, O, and S and where the heteroaryl ring may be optionally mono- or di-substituted with substituent(s) selected from the group consisting of halogen, oxo, thiocarbonyl, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, phenylamino, benzylamino, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, carboxyalkyl of 2-7 carbon atoms, carboalkoxyalkyl of 3-8 carbon atoms, aminoalkyl of 1-5 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-10 carbon atoms, N-alkylaminoalkoxy of 3-9 carbon atoms, N,N-dialkylaminoalkoxy of 4-10 carbon atoms, mercapto, methylmercapto, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, and benzoylamino;  
 m is 0-3;  
 n is 0-1;  
 X is NH, O, S, or NR;  
 R is alkyl of 1-6 carbon atoms;  
 Y and Z are both carbon or N; the ring structure of formula 1 then being a fused 5,6,6 or 6,6,6 tricycle; or one of Y and Z is N, O or S, and the other is a bond between the two end rings; the ring structure of formula 1 then being a fused 5,5, 6 or 6,5,6 tricycle; or one of Y or Z is N with the other being carbon; the ring structure of formula 1 then being a fused 5,6,6 or 6,6,6 tricycle;  
                     
 A and D are each, independently, carbon, N, O, or S;  
 B is carbon or N;  
 the dashed line indicates an optional double bond;  
 R 1 , R 2 , R 3 , and R 4  are each, independently, not present, hydrogen, halogen, hydroxy, amino, hydroxyamino, trifluoromethyl, trifluoromethoxy, mercapto, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, alkynyloxy of 2-106 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, mercaptoalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, cycloalkoxy of 3-8 carbon atoms, alkylthio of 1-6 carbon atoms, cycloalkylthio of 3-8 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulfonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, cyano, nitro, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, alkenoyl of 3-7 carbon atoms, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, phenoxy, phenyl, thiophenoxy, benzyl, alkylamino of 1-6 carbon atoms, alkanoyloxy of 2-7 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, dialkylamino of 2 to 12 carbon atoms, alkanoyloxymethyl group of 2-7 carbon atoms, alkenoyloxymethyl group of 2-7 carbon atoms, alkynoyloxymethyl group of 2-7 carbon atoms, azido, benzoyl, carboxyalkyl of 2-7 carbons, carboalkoxyalkyl of 3-8 carbon atoms,  
                     
 R 5  is independently hydrogen, alkyl of 1-6 carbon atoms, aminoalkyl of 1-6 carbon atoms, N-alkylaminoalkyl of 2-9 carbon atoms, N,N-dialkylaminoalkyl of 3-12 carbon atoms, N-cycloalkylaminoalkyl of 4-12 carbon atoms, N-cycloalkyl-N-alkylaminoalkyl of 5-18 carbon atoms, N,N-dicycloalkylaminoalkyl of 7-18 carbon atoms, morpholino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, piperidino-N-alkyl wherein the alkyl group is 1-6 carbon atoms, N-alkyl-piperazino-N-alkyl wherein either alkyl group is 1-6 carbon atoms, azacycloalkyl-N-alkyl of 3-11 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, alkoxyalkyl of 2-8 carbon atoms, or phenyl;  
 V is (CH 2 ) m , O, S, or NR 6 ;  
 R 7  is NR 6 R 6 , OR 6 , J, N(R 6 ) 3   + , or NR 6 (OR 6 );  
 M is NR 6 , O, S, N—[(C(R 6 ) 2 ) p NR 6 R 6 ], or N—[(C(R 6 ) 2 ) p —OR 6 ];  
 W is NR 6 , O, S, or is a bond;  
 Het is a heterocycle selected from the group consisting of morpholine, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S,S-dioxide, piperidine, pyrrolidine, aziridine, pyridine, imidazole, 1,2,3-triazole, 1,2,4-triazole, thiazole, thiazolidine, tetrazole, piperazine, furan, thiophene, tetrahydrothiophene, tetrahydrofuran, dioxane, 1,3-dioxolane pyrrole, and tetrahydropyran; wherein the heterocycle is optionally mono- or di-substituted on carbon or nitrogen with R 6 ; optionally mono- or di-substituted on carbon with hydroxy, —N(R 6 ) 2 , or —OR 6 ; optionally mono or di-substituted on carbon with the mono-valent radicals —(C(R 6 ) 2 ) s OR 6  or —[(C(R 6 ) 2 ) s N(R 6 ) 2 ]; or optionally mono or di-substituted on a saturated carbon with divalent radicals ═O or —O(C(R 6 ) 2 ) s O—;  
 Ph is a phenyl ring optionally mono-, di- or tri-substituted with halogen, alkyl of 1-6 carbon atoms, trifluoromethyl, nitro, cyano, azido, halomethyl, carboxyl, alkoxycarbonyl, alkylthio, mercapto, mercaptomethyl, —N(R 6 ) 2 , —OR 6 , —(C(R 6 ) 2 ) s OR 6 , —[(C(R 6 ) 2 ) s N(R 6 ) 2 ], or —(C(R 6 ) 2 ) k Het;  
 R 6  is hydrogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 1-6 carbon atoms, alkanoyl of 2-7 carbon atoms, carbamoylalkyl of 2-7 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, hydroxycycloalkyl of 3-6 carbon atoms, or carboxyalkyl of 2-7 carbon atoms; or  
 R 6  is phenyl optionally mono-, di-, or tri-substituted with substituent(s) independently selected from halogen, alkoxy of 1-6 carbon atoms, trifluoromethyl, amino, alkylamino of 1-3 carbon atoms, dialkylamino of 2-6 carbon atoms, nitro, cyano, azido, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, carboxyl, alkoxycarbonyl of 2-7 carbon atoms, phenoxy, phenyl, thiophenoxy, benzoyl, benzyl, phenylamino, benzylamino; alkanoylamino of 1-6 carbon atoms or alkyl of 1-6 carbon atoms;  
 R 8  and R 9  are each, independently, —[(C(R 6 ) 2 ) r NR 6 R 6 ], and —[(C(R 6 ) 2 ) r  OR 6 ];  
 J is independently hydrogen, chlorine, fluorine, or bromine;  
 g=1-6;  
 k=0-4;  
 p=2-4;  
 q=0-4;  
 r=1-4;  
 s=1-6;  
 or a pharmaceutically acceptable salt thereof;  
                     at least one of the bonds between A and B or B and D must be a double bond, with the other being a single bond;    at least one of A, B, and D are not carbon;    only one of A, B, or D can be O or S;    when A, B, or D is O or S, the adjacent atoms must be carbon;    
 provided that when R 5  is bound to a nitrogen atom, the resulting structures do not include —N—C—N— or —O—C—N— radicals; and when R 5  is bound to an oxygen atom, the resulting structures do not include an —N—C—O— radical;  
 provided that when R 6  is alkenyl of 2-7 carbon atoms or alkynyl of 2-7 carbon atoms, the alkenyl or alkynyl moieties are bound to a nitrogen or oxygen atom through a saturated carbon atom in the alkenyl or alkynyl chain;  
 provided that when V is NR 6  and R 7  is NR 6 R 6 , N(R 6 ) 3   + , or NR 6 (OR 6 ), then g=2-6;  
 provided that when M is O or S and R 7  is OR 6 , then p=1-4;  
 provided that when V is NR 6 , O, S, then k=2-4;  
 provided that when V is O or S and M or W is O or S, then k=1-4  
 provided that when W is not a bond with Het bonded through a nitrogen atom then q=2-4; and  
 finally provided when W is a bond with Het bonded through a nitrogen atom and V is O or NR 6  or S, then k=2-4.  
 
   
   
       2 . The compound of  claim 1 , having the structure  
     
       
         
         
             
             
         
       
       or a pharmaceutically acceptable salt thereof.  
     
   
   
       3 . The compound of  claim 1 , having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 X is selected from NH, sulfur or oxygen;  
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       4 . The compound of  claim 1 , having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 X is selected from NH, sulfur, or oxygen;  
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       5 . The compound of  claim 1 , having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 R 2  is hydrogen, amino, trifluoromethyl, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, mercaptoalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, cycloalkoxy of 3-8 carbon atoms, alkylthio of 1-6 carbon atoms, cycloalkylthio of 3-8 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulfonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, cyano, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, phenylamino, benzylamino, phenoxy, phenyl, thiophenoxy, benzyl, alkylamino of 1-6 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, dialkylamino of 2 to 12 carbon atoms,  
                     
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       6 . The compound of  claim 1 , having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 R 2  is hydrogen, amino, trifluoromethyl, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, mercaptoalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, cycloalkoxy of 3-8 carbon atoms, alkylthio of 1-6 carbon atoms, cycloalkylthio of 3-8 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulfonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, cyano, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, phenylamino, benzylamino, phenoxy, phenyl, thiophenoxy, benzyl, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms,  
                     
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       7 . The compound according to  claim 6  wherein R 2  is hydrogen.  
   
   
       8 . The compound of  claim 1 , having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 R 2  and R 3  are hydrogen;  
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       9 . The compound of  claim 1 , having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 R 3  is hydrogen;  
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       10 . The compound of  claim 1 , having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 R 2  is hydrogen, amino, hydroxyamino, trifluoromethyl, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, mercaptoalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, cycloalkoxy of 3-8 carbon atoms, alkylthio of 1-6 carbon atoms, cycloalkylthio of 3-8 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulfonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, cyano, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, phenoxy, phenyl, thiophenoxy, benzyl, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms,  
                     
 R 3  is hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, hydroxyalkyl of 2-6 carbon atoms; mercaptoalkyl of 2-6 carbon atoms, phenyl, benzyl,  
                     
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       11 . The compound of  claim 1 , having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 Ar is a phenyl ring which may be optionally mono-, di- or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, benzoyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2-12 carbon atoms, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, and benzoylamino; or  
 Ar is the radical:  
                     
 R 1  and R 4  are hydrogen;  
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       12 . The compound of  claim 1 , having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 Ar is a phenyl ring which may be optionally mono-, di- or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, benzoyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2-12 carbon atoms, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, and benzoylamino; or  
 Ar is the radical:  
                     
 R 4  is hydrogen and  
 one or two of the substituents R 1 , R 2  and R 3  are as defined above, the remaining being hydrogen;  
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       13 . The compound of  claim 1 , having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 Ar is a phenyl ring which may be optionally mono-, di- or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, benzoyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2-12 carbon atoms, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl,  
 N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, and benzoylamino; or  
 Ar is the radical:  
                     
 R 4  is hydrogen and one or two of the substituents R 1 , R 2  and R 3  are as herein above described, the remaining being hydrogen;  
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       14 . The compound of  claim 1 , having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 Ar is a phenyl ring which may be optionally mono-, di- or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, benzoyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2-12 carbon atoms, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, and benzoylamino; or  
 Ar is the radical:  
                     
 R 2  is hydrogen, amino, trifluoromethyl, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, mercaptoalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, cycloalkoxy of 3-8 carbon atoms, alkylthio of 1-6 carbon atoms, cycloalkylthio of 3-8 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulfonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, cyano, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, phenylamino, benzylamino, phenoxy, phenyl, thiophenoxy, benzyl, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms,  
                     
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       15 . The compound of  claim 1 , having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 Ar is a phenyl ring which may be optionally mono-, di- or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, benzoyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2-12 carbon atoms, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, and benzoylamino; or  
 Ar is the radical:  
                     
 R 2  is hydrogen, amino, trifluoromethyl, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, mercaptoalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, cycloalkoxy of 3-8 carbon atoms, alkylthio of 1-6 carbon atoms, cycloalkylthio of 3-8 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulfonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, cyano, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, phenylamino, benzylamino, phenoxy, phenyl, thiophenoxy, benzyl, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms,  
                     
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       16 . The compound according to  claim 15  wherein R 2  is hydrogen.  
   
   
       17 . The compound of  claim 1 , having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 Ar is a phenyl ring which may be optionally mono-, di- or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, benzoyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2-12 carbon atoms, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alklynoylamino of 3-8 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbanoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, and benzoylamino; or  
 Ar is the radical:  
                     
 R 2  and R 3  are hydrogen;  
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       18 . The compound of  claim 1 , having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 Ar is a phenyl ring which may be optionally mono-, di- or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, benzoyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2-12 carbon atoms, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, and benzoylamino; or  
 Ar is the radical:  
                     
 R 3  is hydrogen;  
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       19 . The compound of  claim 1 , having the structure  
     
       
         
         
             
             
         
       
     
     wherein 
 Ar is a phenyl ring which may be optionally mono-, di- or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, azido, hydroxyalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkanoyloxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, alkylthio of 1-6 carbon atoms, hydroxy, trifluoromethyl, cyano, nitro, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, benzoyl, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 2-12 carbon atoms, alkanoylamino of 1-6 carbon atoms, alkenoylamino of 3-8 carbon atoms, alkynoylamino of 3-8 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, and benzoylamino; or  
 Ar is the radical:  
                     
 R 2  is hydrogen, amino, hydroxyamino, trifluoromethyl, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, alkenyloxy of 2-6 carbon atoms, hydroxyalkyl of 1-6 carbon atoms, mercaptoalkyl of 1-6 carbon atoms, halomethyl, alkoxymethyl of 2-7 carbon atoms, alkoxy of 1-6 carbon atoms, cycloalkoxy of 3-8 carbon atoms, alkylthio of 1-6 carbon atoms, cycloalkylthio of 3-8 carbon atoms, alkylsulphinyl of 1-6 carbon atoms, alkylsulfonyl of 1-6 carbon atoms, alkylsulfonamido of 1-6 carbon atoms, alkenylsulfonamido of 2-6 carbon atoms, alkynylsulfonamido of 2-6 carbon atoms, cyano, carboxy, alkoxycarbonyl of 2-7 carbon atoms, alkanoyl of 2-7 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms, N-alkyl-N-alkenylamino of 4 to 12 carbon atoms, N,N-dialkenylamino of 6-12 carbon atoms, phenylamino, benzylamino, phenoxy, phenyl, thiophenoxy, benzyl, alkylamino of 1-6 carbon atoms, dialkylamino of 2 to 12 carbon atoms, alkanoyloxy of 1-6 carbon atoms, alkenoyloxy of 3-8 carbon atoms, alkynoyloxy of 3-8 carbon atoms, carbamoyl, N-alkylcarbamoyl of 2-7 carbon atoms, N,N-dialkylcarbamoyl of 3-13 carbon atoms,  
                     
 R 3  is hydrogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, hydroxyalkyl of 2-6 carbon atoms; mercaptoalkyl of 2-6 carbon atoms, phenyl, benzyl,  
                     
 or a pharmaceutically acceptable salt thereof.  
 
   
   
       20 . The compound of  claim 1 , which is: 
 a) 4-(4-phenoxyanilino)benzo[g]quinoline-3-carbonitrile,    b) 4-(3-chloro-4-fluoroanilino)benzo[g]quinoline-3-carbonitrile,    c) 4-(4-chloro-5-methoxy-2-methylanilino)benzo[g]quinoline-3-carbonitrile,    d) 7,8-dimethoxy-4-(4-phenoxyanilino)benzo[g]quinoline-3-carbonitrile,    e) 4-(4-chloro-5-methoxy-2-methylanilino)-7,8-dimethoxybenzo[g]quinoline-3-carbonitrile,    f) 4-(3-chloro-4-fluoroanilino)-7,8-dimethoxybenzo[g]quinoline-3-carbonitrile,    g) 4-(2,4-dichloroanilino)-7,8-dimethoxybenzo[g]quinoline-3-carbonitrile,    h) 4-(2,4-dichloroanilino)-7,8-dihydroxybenzo[g]quinoline-3-carbonitrile,    i) 8-(3,4,5-trimethoxyanilino)-3H-[1,2,3]triazolo[4,5-g]quinoline-7-carbonitrile,    j) 9-(4-chloro-5-methoxy-2-methylanilino)pyrido[2,3-g]quinoxaline-8-carbonitrile,    k) 8-(5-methoxy-2-methylanilino)-2-{[2-(4-morpholinyl)ethyl]amino}imidazo[4,5-g]quinoline-7-carbonitrile,    l) 2-{[2-(4-morpholinyl)ethyl]amino}-8-(3,4,5-trimethoxyanilino)imidazo[4,5-g]quinoline-7-carbonitrile,    m) 2-amino-8-(4-phenoxyanilino)imidazo[4,5-g]quinoline-7-carbonitrile,    n) 8-(3-bromo-phenylamino)imidazo[4,5-g]quinoline-7-carbonitrile,    o) 8-(2-bromo-4-chlorophenylamino)imidazo[4,5-g]quinoline-7-carbonitrile,    p) 8-(2-bromo-4-chloro-5-methoxyphenylamino)imidazo[4,5-g]quinoline-7-carbonitrile,    q) 8-(2-chloro-5-methoxyphenylamino)imidazo[4,5-g]quinoline-7-carbonitrile,    r) 8-(3-hydroxy-4-methylphenylamino)imidazo[4,5-g]quinoline-7-carbonitrile,    s) 8-(3,4,5-trimethoxyanilino)imidazo[4,5-g]quinoline-7-carbonitrile,    t) 8-(4-phenoxyanilino)imidazo[4,5-g]quinoline-7-carbonitrile,    u) 2-(chloromethyl)-8-(3,4,5-trimethoxyanilino)imidazo[4,5-g]quinoline-7-carbonitrile,    v) 2-(4-morpholinylmethyl)-8-(3,4,5-trimethoxyanilino)imidazo[4,5-g]quinoline-7-carbonitrile,    w) 8-(4-chloro-5-methoxy-2-methylanilino)-3-[2-(4-morpholinyl)ethyl]-3H-imidazo[4,5-g]quinoline-7-carbonitrile,    x) 3-[2-(4-morpholinyl)ethyl]-8(4-phenoxyanilino)-3H-imidazo[4,5-g]quinoline-7-carbonitrile,    y) 8-[(4-chloro-5-methoxy-2-methylphenyl)amino]-thiazolo[4,5-g]quinoline-7-carbonitrile,    z) 4-(3-bromophenylamino)benzo[4,5]thieno[3,2-b]pyridine-3-carbonitrile,    aa) 4-(4-chloro-2-fluorophenylamino)benzo[4,5]thieno[3,2-b]pyridine-3-carbonitrile,    bb) 4-(2,4-dichlorophenylamino)benzo[4,5]thieno[3,2-b]pyridine-3-carbonitrile,    cc) 4-(2,4-dichloro-5-methoxyphenylamino)benzo[4,5]thieno[3,2-b]pyridine-3-carbonitrile,    dd) 4-(4-phenoxyphenylamino)benzo[4,5]thieno[3,2-b]pyridine-3-carbonitrile,    ee) 4-(3-hydroxy-4-methylphenylamino)benzo[4,5]thieno[3,2-b]pyridine-3-carbonitrile,    ff) 4-(4-chloro-2-fluorophenoxy)benzo[4,5]thieno[3,2-b]pyridine-3-carbonitrile,    gg) 4-(4-chloro-5-methoxy-2-methylphenylamino)-8-nitrobenzo[4,5]thieno[3,2-b]pyridine-3-carbonitrile,    hh) 8-anilino-4-(4-chloro-5-methoxy-2-methylanilino)[1]benzothieno[3,2-b]pyridine-3-carbonitrile,    ii) 4-(3-bromoanilino)-6-nitro[1]benzothieno[3,2-b]pyridine-3-carbonitrile,    jj) 6-amino-4-(3-bromoanilino)[1]benzothieno[3,2-b]pyridine-3-carbonitrile,    kk) 4-(3-bromophenylamino)benzo[4,5]furo[3,2-b]pyridine-3-carbonitrile,    ll) 4-(4-chloro-2-fluorophenylamino)benzo[4,5]furo[3,2-b]pyridine-3-carbonitrile,    mm) 4-(3-hydroxy-4-methylphenylamino)benzo[4,5]furo[3,2-b]pyridine-3-carbonitrile,    nn) 4-(4-phenoxyphenylamino)benzo[4,5]furo[3,2-b]pyridine-3-carbonitrile,    oo) 4-(4-chloro-2-fluorophenoxy)benzo[4,5]furo[3,2-b]pyridine-3-carbonitrile,    pp) 4-(2,4-dichloroanilino)-8-nitro[1]benzothieno[3,2-b]pyridine-3-carbonitrile,    qq) 4-(3-bromoanilino)-8-nitro[1]benzothieno[3,2-b]pyridine-3-carbonitrile,    rr) 8-amino-4-(3-bromoanilino)[1]benzothieno[3,2-b]pyridine-3-carbonitrile,    ss) N-[4-(3-bromoanilino)-3-cyano[1]benzothieno[3,2-b]pyridin-8-yl]acrylamide,    tt) N-[4-(3-bromoanilino)-3-cyano[1]benzothieno[3,2-b]pyridin-6-yl]acrylamide,    uu) 4-(2,4-dichloroanilino)-7-methoxybenzo[g]quinoline-3-carbonitrile,    vv) 4-(2,4-dichloroanilino)-8-methoxybenzo[g]quinoline-3-carbonitrile,    ww) 4-(2,4-dichloroanilino)-7-hydroxybenzo[g]quinoline-3-carbonitrile,    xx) 4-(2,4-dichloroanilino)-8-hydroxybenzo[g]quinoline-3-carbonitrile,    yy) 4-(2,4-dichloroanilino)-7-[2-(dimethylamino)ethoxy]benzo[g]quinoline-3-carbonitrile,    zz) 4-(4-chloro-5-methoxy-2-methylanilino)-7-methoxy-8-(chloroethoxy)benzo[g]quinoline-3-carbonitrile,    aaa) 4-(4-chloro-5-methoxy-2-methylanilino)-8-methoxy-7-(chloroethoxy)benzo[g]quinoline-3-carbonitrile,    bbb) 4-(4-chloro-5-methoxy-2-methylanilino)-7-methoxy-8-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    ccc) 4-(4-chloro-5-methoxy-2-methylanilino)-8-methoxy-7-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    ddd) 4-(2,4-dichloro-5-methoxyanilino)-7-methoxy-8-(chloroethoxy)benzo[g]quinoline-3-carbonitrile,    eee) 4-(2,4-dichloro-5-methoxyanilino)-8-methoxy-7-(chloroethoxy)benzo[g]quinoline-3-carbonitrile,    fff) 4-(2,4-dichloro-5-methoxyanilino)-8-methoxy-7-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    ggg) 4-(2,4-dichloro-5-methoxyanilino)-7-methoxy-8-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    hhh) 4-(2,4-dichloro-5-methoxyanilino)-8-methoxy-7-[2-(4-methyl-1-piperazinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    iii) 4-(2,4-dichloro-5-methoxyanilino)-7-methoxy-8-[2-(4-methyl-1-piperazinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    jjj) 4-(4-chloro-5-methoxy-2-methylanilino)-8-methoxy-7-[2-(4-methyl-1-piperazinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    kkk) 4-(4-chloro-5-methoxy-2-methylanilino)-7-methoxy-8-[2-(4-methyl-1-piperazinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    lll) 4-[3-Chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)phenylamino]-8-hydroxy-7-methoxybenzo[g]quinoline-3-carbonitrile,    mmm) 8-(2-Chloroethoxy)-4-[3-chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)phenylamino]-7-methoxybenzo[g]quinoline-3-carbonitrile,    nnn) 4-[3-Chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)phenylamino]-7-methoxy-8-(2-morpholin-4-yl-ethoxy)benzo[g]quinoline-3-carbonitrile,    ooo) 4-[3-Chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)phenylamino]-8-(3-chloropropoxy)-7-methoxybenzo[g]quinoline-3-carbonitrile,    ppp) 4-[3-Chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)phenylamino]-7-methoxy-8-(3-morpholin-4-yl-propoxy)benzo[g]quinoline-3-carbonitrile,    qqq) 4-[3-Chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)phenylamino]-7-methoxy-8-[2-(4-methylpiperazin-1-yl)ethoxy]-benzo[g]quinoline-3-carbonitrile,    rrr) 4-[3-Chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)phenylamino]-7-methoxy-8-(2-[1,2,3]triazol-2-yl-ethoxy)benzo[g]quinoline-3-carbonitrile,    sss) 4-[3-Chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)phenylamino]-7-methoxy-8-(2-[1,2,3]triazol-1-yl-ethoxy)benzo[g]quinoline-3-carbonitrile,    ttt) 4-(2,4-Dichloro-5-methoxyphenylamino)-8-hydroxy-7-methoxybenzo[g]quinoline-3-carbonitrile,    uuu) 8-(3-Chloropropoxy)-4-(2,4-dichloro-5-methoxyphenylamino)-7-methoxybenzo[g]quinoline-3-carbonitrile,    vvv) 4-(2,4-Dichloro-5-methoxyphenylamino)-7-methoxy-8-(3-morpholin-4-yl-propoxy)benzo[g]quinoline-3-carbonitrile,    www) 4-(2,4-Dichloro-5-methoxyphenylamino)-7-methoxy-8-(2-[1,2,3]triazol-2-yl-ethoxy)benzo[g]quinoline-3-carbonitrile,    xxx) 4-(2,4-Dichloro-5-methoxyphenylamino)-7-methoxy-8-(2-[1,2,3]triazol-1-yl-ethoxy)benzo[g]quinoline-3-carbonitrile,    yyy) 4-(2,4-Dichloro-5-methoxyanilino)-7,8-dimethoxybenzo[b][1,8]naphthyridine-3-carbonitrile,    zzz) 8-(2-Chloroethoxy)-4-(2,4-dichloro-5-methoxyanilino)-7-methoxybenzo[b][1,8]naphthyridine-3-carbonitrile,    aaaa) 4-(2,4-Dichloro-5-methoxyanilino)-7-methoxy-8-[2-(4-morpholinyl)ethoxy]benzo[b][1,8]naphthyridine-3-carbonitrile,    bbbb) 8-(2-Chloroethoxy)-4-{3-chloro-4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]anilino}-7-methoxybenzo[b][1,8]naphthyridine-3-carbonitrile,    cccc) 4-(2,4-Dichloro-5-methoxyanilino)-7-methoxy-8-[2-(4-methyl-1-piperazinyl)ethoxy]benzo[b][1,8]naphthyridine-3-carbonitrile,    dddd)  4 -{3-Chloro-4-[(1-methyl-1H-imidazol-2-yl)sulfanyl]anilino}-7-methoxy-8-[2-(4-morpholinyl)ethoxy]benzo[b][1,8]naphthyridine-3-carbonitrile,    eeee) 4-(2,4-Dichloroanilino)-7,8-dimethoxybenzo[b][1,8]naphthyridine-3-carbonitrile,    ffff) 8-(2-Chloroethoxy)-4-(4-chloro-5-methoxy-2-methylanilino)-7-ethoxybenzo[g]quinoline-3-carbonitrile,    gggg) 8-(2-Chloroethoxy)-4-(2-chloro-4-fluoro-5-methoxyanilino)-7-methoxybenzo[g]quinoline-3-carbonitrile,    hhhh) 7-(2-Chloroethoxy)-4-(2-chloro-4-fluoro-5-methoxyanilino)-8-methoxybenzo[g]quinoline-3-carbonitrile,    iiii) 8-(2-Chloroethoxy)-4-(2-chloro-5-methoxy-4-methylphenylamino)-7-methoxybenzo[g]quinoline-3-carbonitrile,    jjjj) 7-(2-Chloroethoxy)-4-(2-chloro-5-methoxy-4-methylphenylamino)-8-methoxybenzo[g]quinoline-3-carbonitrile,    kkkk) 7-(2-Chloroethoxy)-4-(3-chloro-4-fluoroanilino)-8-methoxybenzo[g]quinoline-3-carbonitrile,    llll) 8-(2-Chloroethoxy)-4-(3-chloro-4-fluoroanilino)-7-methoxybenzo[g]quinoline-3-carbonitrile,    mmmm) 4-(4-Benzyloxy-3-chlorophenylamino)-7-(2-chloroethoxy)-8-methoxybenzo[g]quinoline-3-carbonitrile,    nnnn) 4-(4-Benzyloxy-3-chlorophenylamino)-8-(2-chloroethoxy)-7-methoxybenzo[g]quinoline-3-carbonitrile,    oooo) 7-(2-Chloroethoxy)-4-(3-chloro-4-phenoxyphenylamino)-8-methoxybenzo[g]quinoline-3-carbonitrile,    pppp) 8-(2-Chloroethoxy)-4-(3-chloro-4-phenoxyphenylamino)-7-methoxybenzo[g]quinoline-3-carbonitrile,    qqqq) 4-(4-Chloro-5-methoxy-2-methylanilino)-8-ethoxy-7-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    rrrr) 4-(4-Chloro-5-methoxy-2-methylanilino)-7-ethoxy-8-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    ssss) ({2[4-(4-Chloro-5-methoxy-2-methylphenylamino)-3-cyano-8-ethoxybenzo[g]quinoline-7-yloxy]-ethyl}-ethoxycarbonylmethyl-amino)-acetic acid ethyl ester,    tttt) ({2-[4-(4-Chloro-5-methoxy-2-methylphenylamino)-3-cyano-7-ethoxybenzo[g]quinoline-8-yloxy]-ethyl}-ethoxycarbonylmethylamino)-acetic acid ethyl ester,    uuuu) 2-(Carbamoylmethyl-{2-[4-(4-chloro-5-methoxy-2-methylphenylamino)-3-cyano-7-ethoxybenzo[g]quinolin-8-yloxy]-ethyl}-amino)-acetamide,    vvvv) 4-(2,4-Dichloroanilino)-7-methoxy-8-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    wwww) 4-(2,4-Dichloroanilino)-8-methoxy-7-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    xxxx) 8-Methoxy-7-[2-(4-methyl-1-piperazinyl)ethoxy]-4-(3,4,5-trimethoxyanilino)benzo[g]quinoline-3-carbonitrile,    yyyy) 7-Methoxy-8-[2-(4-methyl-1-piperazinyl)ethoxy]-43,4,5-trimethoxyanilino)benzo[g]quinoline-3-carbonitrile,    zzzz) 7-Methoxy-8-[2-(4-morpholinyl)ethoxy]-4-(3,4,5-trimethoxyanilino)benzo[g]quinoline-3-carbonitrile,    aaaaa) 8-Methoxy-7-[2-(4-morpholinyl)ethoxy]-4-(3,4,5-trimethoxyanilino)benzo[g]quinoline-3-carbonitrile,    bbbbb) 4-(2-Chloro-4-fluoro-5-methoxyanilino)-8-methoxy-7-[2-(4-methyl-1-piperazinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    ccccc) 4-(2-Chloro-5-methoxy-4-methylanilino)-8-methoxy-7-[2-(4-methyl-1-piperazinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    ddddd) 4-(2-Chloro-5-methoxy-4-methylanilino)-7-methoxy-8-[2-(4-methyl-1-piperazinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    eeeee) 4-(2,4-Dichloro-5-methoxyanilino)-7-[2-(4-hydroxy-1-piperidinyl)ethoxy]-8-methoxybenzo[g]quinoline-3-carbonitrile,    fffff) 4-(3-Chloro-4-fluoroanilino)-7-methoxy-8-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    ggggg) 4-(2,4-Dichloro-5-methoxyanilino)-8-[2-(4-hydroxy-1-piperidinyl)ethoxy]-7-methoxybenzo[g]quinoline-3-carbonitrile,    hhhhh) 4-(2-Chloro-5-methoxy-4-methylanilino)-8-methoxy-7-[2-(4-hydroxy-1-piperidinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    iiiii) 4-(2-Chloro-5-methoxy-4-methylanilino)-7-methoxy-8-[2-(4-hydroxy-1-piperidinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    jjjjj) 4-(2-Chloro-4-fluoro-5-methoxyanilino)-8-methoxy-7-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    kkkkk) 4-(2-Chloro-4-fluoro-5-methoxyanilino)-7-methoxy-8-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    lllll) 4-(2-Chloro-4-fluoro-5-methoxyanilino)-7-methoxy-8-[2-(4-methyl-1-piperazinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    mmmmm) 4-(3-Chloro-4-fluoroanilino)-8-methoxy-7-[2-(4-morpholinyl)ethoxy]benzo[g]quinoline-3-carbonitrile,    nnnnn) 4-(3-Chloro-4-phenoxyphenylamino)-7-methoxy-8-(2-morpholin-4-yl-ethoxy)benzo[g]quinoline-3-carbonitrile,    ooooo) 4-(3-Chloro-4-phenoxyphenylamino)-8-methoxy-7-(2-morpholin-4-yl-ethoxy)benzo[g]quinoline-3-carbonitrile,    ppppp) 4-(2-Chloro-5-methoxy-4-methylphenylamino)-8-methoxy-7-(2-morpholin-4-yl-ethoxy)benzo[g]quinoline-3-carbonitrile,    qqqqq) 4-(2-Chloro-5-methoxy-4-methylphenylamino)-7-methoxy-8-(2-morpholin-4-yl-ethoxy)benzo[g]quinoline-3-carbonitrile,    rrrrr) 4-(4-Benzyloxy-3-chlorophenylamino)-8-methoxy-7-(2-morpholin-4-yl-ethoxy)benzo[g]quinoline-3-carbonitrile,    sssss) 4-(4-Benzyloxy-3-chlorophenylamino)-7-methoxy-8-(2-morpholin-4-yl-ethoxy)benzo[g]quinoline-3-carbonitrile,    ttttt) 8-(Benzyloxy)-4-[(2-chloro-4-fluoro-5-methoxyphenyl)amino]-7-methoxybenzo[g]quinoline-3-carbonitrile,    uuuuu) 4-[(2-Chloro-4-fluoro-5-methoxyphenyl)amino]-8-hydroxy-7-methoxybenzo[g]quinoline-3-carbonitrile, 
 or a pharmaceutically acceptable salt thereof.  
   
   
   
       21 . An intermediate compound selected from the group: 
 a) 4-oxo-1,4-dihydrobenzo[g]quinoline-3-carbonitrile,    b) 4-chlorobenzo[g]quinoline-3-carbonitrile,    c) 3-(dimethylaminomethyleneamino)-6,7-dimethoxynaphthalene-2-carboxylic acid methyl ester,    d) 7,8-dimethoxy-4-oxo-1,4-dihydrobenzo[g]quinoline-3-carbonitrile,    e) 4-chloro-7,8-dimethoxybenzo[g]quinoline-3-carbonitrile,    f) 7-chloro-6-nitro-4-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,4-dihydro-3-quinolinecarbonitrile,    g) 6,7-diamino-4-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,4-dihydro-quinoline-3-carbonitrile,    h) 8-oxo-5-{[2-(trimethylsilyl)ethoxy]methyl}-5,8-dihydro[1,2,3]triazolo[4,5-g]quinoline-7-carbonitrile,    i) 8-oxo-5,8-dihydro[1,2,3]triazolo[4,5-g]quinoline-7-carbonitrile,    j) 8-chloro[1,2,3]triazolo[4,5-g]quinoline-7-carbonitrile,    k) 2-amino-8-oxo-5-{[2-(trimethylsilyl)ethoxy]methyl-5,8-dihydroimidazo[4,5-g]quinoline-7-carbonitrile,    l) 2-amino-8-oxo-5,8-dihydroimidazo[4,5-g]quinoline-7-carbonitrile,    m) 2-amino-8-chloroimidazo[4,5-g]quinoline-7-carbonitrile,    n) 8-oxo-5,8-dihydroimidazo[4,5-g]quinoline-7-carbonitrile,    o) 8-chloroimidazo[4,5-g]quinoline-7-carbonitrile,    p) 7-cyanoimidazo[4,5-g]quinolin-8-yl(3,4,5-trimethoxyphenyl)formamide,    q) 7-cyanoimidazo[4,5-g]quinolin-8-yl(4-phenoxyphenyl)formamide,    r) 7-{[2-(4-morpholinyl)ethyl]amino}-6-nitro-4-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,4-dihydro-3-quinolinecarbonitrile,    s) 6-amino-7-{[2-(4-morpholinyl)ethyl]amino}-4-oxo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,4-dihydro-3-quinolinecarbonitrile,    t) 3-[2-(4-morpholinyl)ethyl]-8-oxo-5,8-dihydro-3H-imidazo[4,5-g]quinoline-7-carbonitrile,    u) 8-chloro-3-[2-(4-morpholinyl)ethyl]-3H-imidazo[4,5-g]quinoline-7-carbonitrile,    v) 1,4-dihydro-7-mercapto-6-nitro-4-oxo-1-[[2-(trimethylsilyl)ethoxy]methyl]-3-quinolinecarbonitrile,    w) 8-hydroxy[1,3]thiazolo[4,5-g]quinoline-7-carbonitrile,    x) 3-(dimethylaminomethyleneamino)benzo[b]thiophene-2-carboxylic acid methyl ester,    y) 4-hydroxybenzo[4,5]thieno[3,2-b]pyridine-3-carbonitrile,    z) 4-chlorobenzo[4,5]thieno[3,2-b]pyridine-3-carbonitrile,    aa) 4-hydroxy-8-nitrobenzo[4,5]thieno[3,2-b]pyridine-3-carbonitrile,    bb) 4-chloro-8-nitrobenzo[4,5]thieno[3,2-b]pyridine-3-carbonitrile,    cc) 4-chloro-6-nitro[1]benzothieno[3,2-b]pyridine-3-carbonitrile,    dd) 3-(dimethylaminomethyleneamino)benzofuran-2-carboxylic acid ethyl ester,    ee) 4-hydroxybenzo[4,5]furo[3,2-b]pyridine-3-carbonitrile,    ff) 4-chlorobenzo[4,5]furo[3,2-b]pyridine-3-carbonitrile,    gg) 7-methoxy-4-oxo-1,4-dihydrobenzo[g]quinoline-3-carbonitrile,    hh) 8-methoxy-4-oxo-1,4-dihydrobenzo[g]quinoline-3-carbonitrile,    ii) 4-chloro-7-methoxybenzo[g]quinoline-3-carbonitrile,    jj) 4-chloro-8-methoxybenzo[g]quinoline-3-carbonitrile,    kk) ethyl 7-(2-chloroethoxy)-6-methoxy-3-nitro-2-naphthoate,    ll) ethyl 6-(2-chloroethoxy)-7-methoxy-3-nitro-2-naphthoate,    mm) ethyl 3-amino-7-(2-chloroethoxy)-6-methoxy-2-naphthoate,    nn) ethyl 3-amino-6-(2-chloroethoxy)-7-methoxy-2-naphthoate,    oo) 8-(2-chloroethoxy)-7-methoxy-4-oxo-1,4-dihydrobenzo[g]quinoline-3-carbonitrile,    pp) 7-(2-chloroethoxy)-8-methoxy-4-oxo-1,4-dihydrobenzo[ ]quinoline-3-carbonitrile,    qq) 4-chloro-7-methoxy-8-(2-chloroethoxy)benzo[g]quinoline-3-carbonitrile,    rr) 4-chloro-8-methoxy-7-(2-chloroethoxy)benzo[g]quinoline-3-carbonitrile,    ss) 7,8-dimethoxy-4-oxo-1,4-dihydrobenzo[b][1,8] naphthyridine-3-carbonitrile,    tt) 4-chloro-7,8-dimethoxybenzo[b][1,8]naphthyridine-3-carbonitrile,    uu) 8-(2-chloroethoxy)-7-methoxy-4-oxo-1,4-dihydrobenzo[b][1,8]naphthyridine-3-carbonitrile, and    vv) 4-chloro-8-(2-chloroethoxy)-7-methoxybenzo[b][1,8]naphthyridine-3-carbonitrile.    
   
   
       22 . A method of treating, inhibiting the growth of, or eradicating a neoplasm in a mammal in need thereof which comprises providing to said mammal an effective amount of a compound as described in  claim 1 .  
   
   
       23 . The method according to  claim 22  wherein the neoplasm is selected from the group consisting of breast, kidney, bladder, mouth, larynx, esophagus, stomach, colon, ovary, lung, pancreas, liver, prostate, and skin.  
   
   
       24 . The method according to  claim 22  wherein the neoplasm expresses EGFR or erbB2 (Her2).  
   
   
       25 . The method according to  claim 22  wherein the neoplasm depends, at least in part, on the MAPK pathway.  
   
   
       26 . The method acording to  claim 22  wherein the neoplasm depends, at least in part, on the RAF kinase pathway.  
   
   
       27 . The method acording to  claim 22  wherein the neoplasm depends, at least in part, on the SRC kinase pathway.  
   
   
       28 . The method according to  claim 22  wherein the neoplasm depends, at least in part, on the ECK/LERK-1 pathway.  
   
   
       29 . The method according to  claim 22  wherein the neoplasm depends, at least in part, on the VEGF/KDR pathway.  
   
   
       30 . A method of treating, inhibiting the progression of, or eradicating polycystic kidney disease in a mammal in need thereof which comprises providing to said mammal an effective amount of a compound described in  claim 1 .  
   
   
       31 . A method of treating, inhibiting, or eradicating colonic polyps in a mammal in need thereof which comprises providing to said mammal an effective amount of a compound described in  claim 1 .  
   
   
       32 . A method of inhibiting the biological effects of a deregulated protein kinase in a mammal which comprises providing to said mammal an, effective amount of a compound described in  claim 1 .  
   
   
       33 . A method of treating a disease or inhibiting a disease state whose etiology is at least in part caused by a defect in a signaling pathway upstream from a protein kinase; by overexpression of a protein kinase; or by a dysregulated protein kinase in a mammal in need thereof which comprises providing to said mammal an effective amount of a compound described in  claim 1 .  
   
   
       34 . A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and a compound described in  claim 1 .  
   
   
       35 . A process for the preparation of a compound as described in the specification for any of Flowsheets 1″, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14.