Quinoline and quinazoline derivatives and drugs containing the same

Abstract

There are provided compounds which can be used in the treatment of diseases mediated by the autophosphorylation of a PDGF receptor, specifically, compounds which can inhibit neointima formation hypertrophy. The compounds are those represented by formula (I) or pharmacologically acceptable salts or solvates thereof: wherein R 1 and R 2 represent hydrogen, alkyl or the like; R 3 , R 4 , R 5 , and R 6 represent hydrogen, halogen, alkyl, alkoxy or the like; R 11 and R 12 represent hydrogen, alkyl, alkylcarbonyl or the like; and A represents any one of formulae (i) to (x), provided that compounds wherein R 3 , R 4 , R 5 and R 6 represent hydrogen and A represents group (v) wherein u is 0 (zero) and R 19 represents phenyl optionally substituted by halogen, alkyl, or alkoxy are excluded.

1 . A compound represented by formula (1) or a pharmacologically acceptable salt or solvate thereof:  
     
       
         
         
             
             
         
       
     
     wherein 
 X and Z, which may be the same or different, represent CH or N;  
 R 1  and R 2 , which may be the same or different, represent a hydrogen atom or C 1-4  alkoxy optionally substituted by a halogen atom;  
 R 3 , R 4 , R 5 , and R 6 , which may be the same or different, represent a hydrogen atom; a halogen atom; C 1-4  alkyl optionally substituted by a halogen atom; C 1-4  alkoxy optionally substituted by a halogen atom; nitro; amino; or morpholyl;  
 A represents a group selected from the group consisting of formulae (i) to (x), wherein R 11  and R 12 , which may be the same or different, represent a hydrogen atom, C 1-4  alkyl optionally substituted by a halogen atom, or C 1-4  alkylcarbonyl optionally substituted by a halogen atom;  
 provided that compounds wherein R 3 , R 4 , R 5  and R 6  represent a hydrogen atom and A represents group (v) wherein u is 0 (zero) and R 19  represents phenyl optionally substituted by a halogen atom, C 1-4  alkyl, or C 1-4  alkoxy are excluded:  
                     
 wherein  
 i is an integer of 0 to 10,  
 R 13  and R 14 , which may be the same or different, represent a hydrogen atom; C 1-6  alkyl optionally substituted by a halogen atom; or phenyl optionally substituted by a halogen atom or C 1-4  alkyl optionally substituted by a halogen atom,  
 R 13  and R 14  may form a five- to seven-membered saturated or unsaturated heterocyclic ring optionally containing one or more additional hetero-atoms together with the nitrogen atom to which they are attached, and this heterocyclic ring is optionally substituted by a halogen atom or C 1-4  alkyl optionally substituted by a halogen atom, or, R 13  or R 14  may form C 1-4  alkylene optionally substituted by a halogen atom together with R 12 ;  
                     
 wherein  
 j is an integer of 0 to 3,  
 k is an integer of 0 to 3, provided that  
 both j and k are not 0 (zero),  
 m is an integer of 0 to 2,  
 carbon atoms in the following  
                     
 are optionally substituted by one or more C 1-4  alkyl groups, which may be the same or different, optionally substituted by a halogen atom, and  
 R 15  represents a hydrogen atom; cyclic C 3-7  alkyl optionally substituted by a halogen atom; phenyl optionally substituted by C 1-6  alkyl or a halogen atom; or C 1-4  alkoxycarbonyl;  
                     
 wherein  
 n is 0 (zero) or 1,  
 p is an integer of 0 to 10, and  
 R 16  and R 7 , which may be the same or different, represent a hydrogen atom; C 1-6  alkyl optionally substituted by a halogen atom; C 1-4  alkylcarbonyl optionally substituted by a halogen atom; cyclic C 3-7  alkyl optionally substituted by C 1-4  alkyl optionally substituted by a halogen atom; or phenyl optionally substituted by a halogen atom or C 1-4  alkyl optionally substituted by a halogen atom, or  
 R 16  and R 17  may form a five- to seven-membered saturated or unsaturated heterocyclic ring optionally containing one or more additional hetero-atoms together with the nitrogen atom to which they are attached, this heterocyclic ring is optionally condensed with another one or two carbocyclic or heterocyclic ring to form a ten- to twelve-membered saturated or unsaturated bicyclic carbocyclic ring or heterocyclic ring or a ten- to fifteen-membered saturated or unsaturated tricyclic carbocyclic ring or heterocyclic ring, and these heterocyclic rings are optionally substituted by an oxygen atom or C 1-4  alkyl optionally substituted by a halogen atom;  
                     
 wherein  
 q is 0 (zero) or 1,  
 r is an integer of 0 to 3,  
 s is an integer of 0 to 3, provided that  
 both r and s are not 0 (zero),  
 t is an integer of 0 to 2,  
 carbon atoms in the following  
                     
 are optionally substituted by one or more C 1-4  alkyl groups, which may be the same or different, and  
 R 18  represents a hydrogen atom; phenyl optionally substituted by a halogen atom or C 1-6  alkyl optionally substituted by a halogen atom; or C 1-4  alkoxycarbonyl optionally substituted by a halogen atom;  
                     
 wherein  
 u is 0 (zero) or 1,  
 R 19  represents  
 (1) phenyl which is optionally substituted by C 1-10  alkyl optionally substituted by a halogen atom; C 1-10  alkoxy optionally substituted by a halogen atom; —NR 31 R 32  wherein R 31  and R 32 , which may be the same or different, represent a hydrogen atom or C 1-4  alkyl optionally substituted by a halogen atom; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,  
 (2) phenoxy of which the phenyl portion is optionally substituted by C 1-10  alkyl optionally substituted by a halogen atom; C 1-10  alkoxy optionally substituted by a halogen atom; —NR 31 R 32  wherein R 31  and R 32  are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,  
 (3) cyclic C 3-7  alkyl which is optionally condensed with another carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring and the carbocyclic ring and the heterocyclic ring are optionally substituted by C 1-4  alkyl optionally substituted by a halogen atom; phenyl optionally substituted by a halogen atom; cyclic C 3-7  alkyl optionally substituted by a halogen atom; or a halogen atom,  
 (4) a five- to seven-membered saturated or unsaturated heterocyclic ring which is optionally condensed with another carbocyclic or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring optionally substituted by C 1-4  alkyl optionally substituted by a halogen atom, or a halogen atom,  
 (5) C 1-16  alkyl,  
 (6) C 2-6  alkenyl, or  
 (7) C 2-6  alkynyl,  
 wherein (5) C 1-16  alkyl, (6) C 2-6  alkenyl, and (7) C 2-6  alkynyl are optionally substituted by one or more of the following groups:  
 (a) phenyl optionally substituted by C 1-10  alkyl optionally substituted by a halogen atom; C 1-10  alkoxy optionally substituted by a halogen atom; —NR 31 R 32  wherein R 31  and R 32  are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,  
 (b) phenoxy of which the phenyl portion is optionally substituted by C 1-10  alkyl optionally substituted by a halogen atom; C 1-10  alkoxy optionally substituted by a halogen atom; —NR 31 R 32  wherein R 31  and R 32  are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,  
 (c) phenylthio of which the phenyl portion is optionally substituted by C 1-10  alkyl optionally substituted by a halogen atom; C 1-10  alkoxy optionally substituted by a halogen atom; —NR 31 R 32  wherein R 31  and R 32  are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,  
 (d) —NR 33 R 34  wherein R 33  and R 34  are as defined in R 13  and R 14 ,  
 (e) cyclic C 3-7  alkyl which is optionally condensed with another carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring and the carbocyclic ring and the heterocyclic ring are optionally substituted by C 1-4  alkyl optionally substituted by a halogen atom; phenyl optionally substituted by a halogen atom; or a halogen atom,  
 (f) a five- to seven-membered saturated or unsaturated heterocyclic ring which is optionally condensed with another carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring optionally substituted by C 1-4  alkyl optionally substituted by a halogen atom, or a halogen atom,  
 (g) naphthyl,  
 (h) cyano,  
 (i) C 1-4  alkylthio optionally substituted by a halogen atom,  
 (j) a halogen atom, or  
 (k) alkoxycarbonyl optionally substituted by a halogen atom;  
                     
 wherein  
 R 20  represents  
 (1) phenyl optionally substituted by C 1-6  alkyl optionally substituted by a halogen atom; C 1-6  alkoxy optionally substituted by a halogen atom; —NR 35 R 36  wherein R 35  and R 36 , which may be the same or different, represent a hydrogen atom or C 1-4  alkyl optionally substituted by a halogen atom; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,  
 (2) cyclic C 3-7  alkyl which is optionally condensed with another carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring and the carbocyclic ring and the heterocyclic ring are optionally substituted by C 1-4  alkyl optionally substituted by a halogen atom, or a halogen atom,  
 (3) a five- to seven-membered saturated or unsaturated heterocyclic ring which is optionally condensed with another carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring optionally substituted by C 1-4  alkyl optionally substituted by a halogen atom, or a halogen atom,  
 (4) C 1-20  alkyl,  
 (5) C 2-6  alkenyl, or  
 (6) C 2-6  alkynyl, and  
 wherein (4) C 1-20  alkyl, (5) C 2-6  alkenyl, and (6) C 2-6  alkynyl are optionally substituted by one or more of the following groups:  
 (a) phenyl optionally substituted by C 1-6  alkyl optionally substituted by a halogen atom; C 1-6  alkoxy optionally substituted by a halogen atom; —NR 35 R 36  wherein R 35  and R 36  are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,  
 (b) phenoxy of which the phenyl portion is optionally substituted by C 1-6  alkyl optionally substituted by a halogen atom; C 1-6  alkoxy optionally substituted by a halogen atom; —NR 35 R 36  wherein R 35  and R 36  are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,  
 (c) phenylthio of which the phenyl portion is optionally substituted by C 1-6  alkyl optionally substituted by a halogen atom; C 1-6  alkoxy optionally substituted by a halogen atom; —NR 35 R 36  wherein R 35  and R 36  are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,  
 (d) —NR 37 R 38  wherein R 37  and R 38  are as defined in R 13  and R 14 ,  
 (e) cyclic C 3-7  alkyl which is optionally condensed with another carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring and the carbocyclic ring and the heterocyclic ring are optionally substituted by C 1-4  alkyl optionally substituted by a halogen atom, or a halogen atom,  
 (f) a five- to seven-membered saturated or unsaturated heterocyclic ring which is optionally condensed with another carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring optionally substituted by C 1-4  alkyl optionally substituted by a halogen atom, or a halogen atom,  
 (g) naphthyl, or  
 (h) cyano;  
                     
 wherein  
 v is an integer of 0 to 2,  
 R 21  represents  
 (1) phenyl optionally substituted by C 1-6  alkyl optionally substituted by a halogen atom; C 1-6  alkoxy optionally substituted by a halogen atom; —NR 39 R 40  wherein R 39  and R 40 , which may be the same or different, represent a hydrogen atom or C 1-4  alkyl optionally substituted by a halogen atom; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,  
 (2) cyclic C 3-7  alkyl which is optionally condensed with another carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring and the carbocyclic ring and the heterocyclic ring are optionally substituted by C 1-4  alkyl optionally substituted by a halogen atom, or a halogen atom,  
 (3) a five- to seven-membered saturated or unsaturated heterocyclic ring which is optionally condensed with another carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring optionally substituted by C 1-4  alkyl optionally substituted by a halogen atom, or a halogen atom,  
 (4) C 1-20  alkyl,  
 (5) C 2-6  alkenyl, or  
 (6) C 2-6  alkynyl, and  
 wherein (4) C 1-20  alkyl, (5) C 2-6  alkenyl, and (6) C 2-6  alkynyl are optionally substituted by one or more of the following groups:  
 (a) phenyl optionally substituted by C 1-6  alkyl optionally substituted by a halogen atom; C 1-6  alkoxy optionally substituted by a halogen atom; —NR 39 R 40  wherein R 39  and R 40  are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,  
 (b) phenoxy of which the phenyl portion is optionally substituted by C 1-6  alkyl optionally substituted by a halogen atom; C 1-6  alkoxy optionally substituted by a halogen atom; —NR 39 R 40  wherein R 39  and R 40  are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,  
 (c) phenylthio of which the phenyl portion is optionally substituted by C 1-6  alkyl optionally substituted by a halogen atom; C 1-6  alkoxy optionally substituted by a halogen atom; —NR 39 R 40  wherein R 39  and R 40  are as defined above; phenyl optionally substituted by a halogen atom; a halogen atom; or cyano,  
 (d) —NR 41 R 42  wherein R 41  and R 42  are as defined in R 13  and R 14 ,  
 (e) cyclic C 3-7  alkyl which is optionally condensed with another carbocyclic ring or heterocyclic ring to form an eight- to twelve-membered bicyclic saturated or unsaturated carbocyclic ring or heterocyclic ring and the carbocyclic ring and the heterocyclic ring are optionally substituted by C 1-4  alkyl optionally substituted by a halogen atom, or a halogen atom,  
 (f) a five- to seven-membered saturated or unsaturated heterocyclic ring which is optionally condensed with another carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring optionally substituted by C 1-4  alkyl optionally substituted by a halogen atom, or a halogen atom,  
 (g) naphthyl, or  
 (h) cyano;  
                     
 wherein  
 w is an integer of 1 to 4,  
 L represents —O—, —S(═O)y-, wherein y is an integer of 0 to 2, or —N(—R 11 )—,  
 M represents —O—, —C(═O)—O—, —S(═O)z-, wherein z is an integer of 0 to 2, —N(—R 12 )—, —C(═O)—N(—R 12 )—, or —C(═O)—,  
 R 22  represents a hydrogen atom; C 1-4  alkyl optionally substituted by a halogen atom;  
 or phenyl optionally substituted by C 1-4  alkyl optionally substituted by a halogen atom, C 1-4  alkoxy optionally substituted by a halogen atom, nitro, amino, or a halogen atom,  
 when M represents —N(—R 12 )— or —C(═O)—N(—R 12 )—, R 22  and R 12  may form a five- to seven-membered saturated or unsaturated heterocyclic ring optionally containing one or more additional hetero-atoms together with the nitrogen atom to which they are attached, this heterocyclic ring is optionally condensed with another carbocyclic ring or heterocyclic ring to form a ten- to twelve-membered bicyclic saturated or unsaturated heterocyclic ring, and these heterocyclic rings are optionally substituted by C 1-4  alkyl optionally substituted by a halogen atom; phenyl; benzyl; or piperidine;  
   —OR 23   (ix)  
 wherein R 23  represents a hydrogen atom or C 1-4  alkyl optionally substituted by a halogen atom; and  
   —NR 24 R 25   (x)  
 wherein R 24  and R 25 , which may be the same or different, represent a hydrogen atom or C 1-4  alkyl optionally substituted by a halogen atom.  
 
   
   
       2 . The compound according to  claim 1 , wherein X represents CH or N and Z represents CH.  
   
   
       3 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy and at least one of R 3 , R 4 , R 5 , and R 6  represents a group other than a hydrogen atom.  
   
   
       4 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy, R 3  represents a group other than a hydrogen atom, and R 4 , R 5 , and R 6  represent a hydrogen atom.  
   
   
       5 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy and A represents group (i) wherein i is an integer of 1 to 3; and R 13  and R 4 , which may be the same or different, represent C 1-4  alkyl, or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C 1-4  alkyl together with the nitrogen atom to which they are attached.  
   
   
       6 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy, R 3 , R 4 , R 5 , and R 6  represent a hydrogen atom, and A represents group (i) wherein i is an integer of 1 to 3 and R 13  and R 4 , which may be the same or different, represent C 1-4  alkyl, or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C 1-4  alkyl together with the nitrogen atom to which they are attached.  
   
   
       7 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy, R 3  represents a group other than a hydrogen atom, R 4 , R 5 , and R 6  represent a hydrogen atom, and A represents group (i) wherein i is an integer of 1 to 3 and R 13  and R 14 , which may be the same or different, represent C 1-4  alkyl, or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C 1-4  alkyl together with the nitrogen atom to which they are attached.  
   
   
       8 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy, R 3  represents nitro, R 4 , R 5 , and R 6  represent a hydrogen atom, and A represents group (i) wherein i is an integer of 1 to 3 and R 13  and R 14 , which may be the same or different, represent C 1-4  alkyl, or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C 1-4  alkyl together with the nitrogen atom to which they are attached.  
   
   
       9 . The compound according to  claim 1 , wherein X represents N, Z represents CH, R 1  and R 2  represent C 1-4  alkoxy, R 3  represents nitro, R 4 , R 5 , and R 6  represent a hydrogen atom, and A represents group (i) wherein i is an integer of 1 to 3 and R 13  and R 14 , which may be the same or different, represent C 1-4  alkyl, or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C 1-4  alkyl together with the nitrogen atom to which they are attached.  
   
   
       10 . The compound according to  claim 1 , wherein X represents N, Z represents CH, R 1  and R 2  represent C 1-4  alkoxy, R 3  represents nitro, R 4 , R 5 , and R 6  represent a hydrogen atom, and A represents group (i) wherein i is 2 and R 13  and R 14 , which may be the same or different, represent C 2-3  alkyl, or may form a six-membered saturated heterocyclic ring optionally substituted by C 1-4  alkyl together with the nitrogen atom to which they are attached.  
   
   
       11 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy and A represents group (ii) wherein j is 1 or 2, k is 1 or 2, m is 1 or 2, and R 15  represents optionally substituted phenyl.  
   
   
       12 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy, R 3 , R 4 , R 5 , and R 6  represent a hydrogen atom, and A represents group (ii) wherein j is 1 or 2, k is 1 or 2, m is 1 or 2, and R 15  represents optionally substituted phenyl.  
   
   
       13 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy, R 3  represents a group other than a hydrogen atom, R 4 , R 5 , and R 6  represent a hydrogen atom, and A represents group (ii) wherein j is 1 or 2, k is 1 or 2, m is 1 or 2, and R 15  represents optionally substituted phenyl.  
   
   
       14 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy and A represents group (iii) wherein n is 0 (zero); p is an integer of 1 to 3; and R 16  and R 17 , which may be the same or different, represent C 1-4  alkyl, or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C 1-4  alkyl or an oxygen atom together with the nitrogen atom to which they are attached.  
   
   
       15 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy, R 3 , R 4 , R 5  and R 6  represent a hydrogen atom, and A represents group (iii) wherein n is 0 (zero); p is an integer of 1 to 3; and R 16  and R 7 , which may be the same or different, represent C 1-4  alkyl, or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C 1-4  alkyl or an oxygen atom together with the nitrogen atom to which they are attached.  
   
   
       16 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy, R 3  represents a group other than a hydrogen atom, R 4 , R 5  and R 6  represent a hydrogen atom, and A represents group (iii) wherein n is 0 (zero), p is an integer of 1 to 3, and R 16  and R 17 , which may be the same or different, represent C 1-4  alkyl, or may form a five- to seven-membered saturated heterocyclic ring optionally substituted by C 1-4  alkyl or an oxygen atom together with the nitrogen atom to which they are attached.  
   
   
       17 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy and A represents group (iv) wherein q is 0 (zero), r is 1 or 2, s is 1 or 2, t is 1 or 2, and R 18  represents optionally substituted phenyl.  
   
   
       18 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy, R 3 , R 4 , R 5  and R 6  represent a hydrogen atom, and A represents group (iv) wherein q is 0 (zero), r is 1 or 2, s is 1 or 2, t is 1 or 2, and R 18  represents optionally substituted phenyl.  
   
   
       19 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy, R 3  represents a group other than a hydrogen atom, R 4 , R 5 , and R 6  represent a hydrogen atom, and A represents group (iv) wherein q is 0 (zero), r is 1 or 2, s is 1 or 2, t is 1 or 2, and R 18  represents optionally substituted phenyl.  
   
   
       20 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy and A represents group (v) wherein u is 1 and R 19  represents optionally substituted phenyl, or C 1-4  alkyl substituted by optionally substituted phenyl.  
   
   
       21 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy, R 3 , R 4 , R 5 , and R 6  represent a hydrogen atom, and A represents group (v) wherein u is 1 and R 19  represents optionally substituted phenyl, or C 1-4  alkyl substituted by optionally substituted phenyl.  
   
   
       22 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy, R 5  represents a group other than a hydrogen atom, R 3 , R 4 , and R 6  represent a hydrogen atom, and A represents group (v) wherein u is 1 and R 19  represents optionally substituted phenyl, or C 1-4  alkyl substituted by optionally substituted phenyl.  
   
   
       23 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy and A represents group (vi) wherein R 20  represents optionally substituted phenyl, or C 1-6  alkyl optionally substituted by optionally substituted phenyl.  
   
   
       24 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy and A represents group (vii) wherein R 21  represents optionally substituted phenyl, or C 1-6  alkyl optionally substituted by optionally substituted phenyl.  
   
   
       25 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy and A represents group (viii) wherein w is an integer of 1 to 3, L represents —O—, M represents —O— or —C(═O)—O—, and R 22  represents optionally substituted phenyl.  
   
   
       26 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy and A represents group (viii) wherein, when L represents —O—, M represents —O—, —C(═O)—O—, —N(—R 12 )—, —C(═O)—N(—R 12 )—, or —C(═O)—; when L represents —S(═O)y-, M represents —O—; and, when L represents —N(—R 11 )—, M represents —O—.  
   
   
       27 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy and A represents group (iii) wherein n is 1 and p is 0 (zero).  
   
   
       28 . The compound according to  claim 1 , wherein R 1  and R 2  represent C 1-4  alkoxy, R 3  represents morpholyl, R 4 , R 5 , and R 6  represent a hydrogen atom, and A represents group (x).  
   
   
       29 . A compound selected from the group consisting of the following compounds or pharmacologically acceptable salts or solvates thereof: 
 N-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}-N′-(2-piperidinoethyl)urea; and    N-[2-(diethylamino)ethyl]-N′-{4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-2-nitrophenyl}urea.    
   
   
       30 . A pharmaceutical composition comprising 
 the compound according to  claim 1  or a pharmacologically acceptable salt or solvate thereof.    
   
   
       31 . The pharmaceutical composition according to  claim 30 , which contains an amount of said compound effective to treat a disease mediated by the autophosphorylation of a PDGF receptor.  
   
   
       32 . The pharmaceutical composition according to  claim 31 , wherein the disease mediated by the autophosphorylation of the PDGF receptor is selected from the group consisting of ischemic diseases involving blood vessel occlusion or angiostenosis induced by angiopathy; ischemic diseases involving blood vessel occlusion or angiostenosis induced by vascular autotransplantation or allotransplantation; and diseases involving cell proliferation and organ fibrosis induced by PDGF, including chronic rheumatism, PDGF-dependent tumors such as glioma, cirrhosis, pulmonary fibrosis, and occlusion of arteriovenous shunt.  
   
   
       33 . The pharmaceutical composition according to  claim 30 , which contains an amount of said compound effective to inhibit angiostenosis.