4-anilino quinazoline derivatives as antiproliferative agents

Abstract

The invention concerns quinazoline derivatives of Formula (I) wherein each of Q 1 , Z, R 1 and Q 2 have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumours which are sensitive to inhibition of erbB receptor tyrosine kinases.

1 . A quinazoline derivative of the Formula I:  
       
         
           
           
               
               
           
         
       
       wherein: 
 G 1  and G 2  each independently is halogeno;  
 X 1  is a direct bond or O;  
 R 1  is selected from hydrogen and (1-6C)alkyl, wherein the (1-6C)alkyl group is optionally substituted by one or more substituents, which may be the same or different, selected from hydroxy and halogeno, and/or a substituent selected from amino, nitro, carboxy, cyano, halogeno, (1-6C)alkoxy, hydroxy(1-6C)alkoxy, (2-8C)alkenyl, (2-8C)alkynyl, (1-6C)alkylthio, (1-6C)alkylsulfinyl, (1-6C)alkylsulfonyl, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, carbamoyl,  N -(1-6C)alkylcarbamoyl,  N , N  di-[(1-6C)alkyl]carbamoyl, (2-6C)alkanoyl, (2-6C)alkanoyloxy, (2-6C)alkanoylamino,  N -(1-6C)alkyl-(2-6C)alkanoylamino, (1-6C)alkoxycarbonyl, sulfamoyl,  N -(1-6C)alkylsulfamoyl,  N , N -di-[(1-6C)alkyl]sulfamoyl, (1-6C)alkanesulponylamino and  N -(1-6C)alkyl-(1-6C)alkanesulfonylamino;  
 X 2  is a direct bond or [CR 2 R 3 ] m , wherein m is an integer from 1 to 6, and each of R 2  and R 3  independently is selected from hydrogen, hydroxy, (1-4C)alkyl and hydroxy(1-4C)alkyl;  
 Q 1  is (3-7C)cycloalkyl or heterocyclyl, wherein Q 1  optionally bears 1, 2 or 3 substituents, which may be the same or different, selected from halogeno, trifluoromethyl, trifluoromethoxy, cyano, nitro, hydroxy, amino, carboxy, carbamoyl, acryloyl, (1-6C)alkyl, (2-8C)alkenyl, (2-8C)alkynyl, (1-6C)alkoxy, (2-6C)alkenyloxy, (2-6C)alkynyloxy, (1-6C)alkylthio, (2-6C)alkenylthio, (2-6C)alkynylthio, (1-6C)alkylsulfinyl, (2-6C)alkenylsulfinyl, (2-6C)alkynylsulfinyl, (1-6C)alkylsulfonyl, (2-6C)alkenylsulfonyl, (2-6C)alkynylsulfonyl, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, (1-6C)alkoxycarbonyl,  N -(1-6C)alkylcarbamoyl,  N , N -di-[(1-6C)alkyl]carbamoyl, (2-6C)alkanoyl, (2-6C)alkanoyloxy, (2-6C)alkanoylamino,  N -(1-6C)alkyl-(2-6C)alkanoylamino, sulfamoyl,  N -(1-6C)alkylsulfamoyl,  N , N -di-[(1-6C)alkyl]sulfamoyl, (1-6C)alkanesulfonylamino,  N -(1-6C)alkyl-(1-6C)alkanesulfonylamino, carbamoyl(1-6C)alkyl,  N -(1-6C)alkylcarbamoyl(1-6C)alkyl,  N , N -di-[(1-6C)alkyl]carbamoyl(1-6C)alkyl, sulfamoyl(1-6C)alkyl,  N -(1-6C)alkylsulfamoyl(1-6C)alkyl,  N , N -di-[(1-6C)alkyl]sulfamoyl(1-6C)alkyl, (2-6C)alkanoyl(1-6C)alkyl, (2-6C)alkanoyloxy(1-6C)alkyl, (2-6C)alkanoylamino(1-6C)alkyl,  N -(1-6C)alkyl-(2-6C)alkanoylamino(1-6C)alkyl and (1-6C)alkoxycarbonyl(1-6C)alkyl, or from a group of the formula:  
   Q 2 -X 3 — 
 wherein X 3  is CO and Q 2  is heterocyclyl, 
 and wherein Q 2  optionally bears 1 or 2 substituents, which may be the same or different, selected from halogeno, hydroxy, (1-4C)alkyl, (2-4C)alkanoyl and (1-4C)alkylsulfonyl,  
 and wherein any (1-6C)alkyl, (2-8C)alkenyl, (2-8C)alkynyl and (2-6C)alkanoyl group within Q 1  optionally bears one or more substituents which may be the same or different selected from halogeno, hydroxy and (1-6C)alkyl and/or optionally a substituent selected from cyano, nitro, carboxy, (2-8C)alkenyl, (2-8C)alkynyl, (1-6C)alkoxy, hydroxy(1-6C)alkoxy, (1-4C)alkoxy(1-6C)alkoxy, (2-6C)alkanoyl, (2-6C)alkanoyloxy and NR a R b , wherein R a  is hydrogen or (1-4C)alkyl and R b  is hydrogen or (1-4C)alkyl, and wherein any (1-4C)alkyl in R a  or R b  optionally bears one or more substituents, which may be the same or different, selected from halogeno and hydroxy and/or optionally a substituent selected from cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)alkoxy, hydroxy(1-4C)alkoxy and (1-2C)alkoxy(1-4C)alkoxy,  
 or R a  and R b  together with the nitrogen atom to which they are attached form a 4, 5 or 6 membered ring, which optionally bears 1 or 2 substituents, which may be the same or different, on an available ring carbon atom selected from halogeno, hydroxy, (1-4C)alkyl and (1-3C)alkylenedioxy, and may optionally bear on any available ring nitrogen a substituent (provided the ring is not thereby quaternised) selected from (1-4C)alkyl, (2-4C)alkanoyl and (1-4C)alkylsulfonyl,  
 and wherein any (1-4C)alkyl or (2-4C)alkanoyl group present as a substituent on the ring formed by R a  and R b  together with the nitrogen atom to which they are attached optionally bears one or more substituents, which may be the same or different, selected from halogeno and hydroxy and/or optionally a substituent selected from (1-4C)alkyl and (1-4C)alkoxy;  
 and wherein any heterocyclyl group within the Q 1 -X 2 — group optionally bears 1 or 2 oxo (═O) or thioxo (═S) substituents;  
 or a pharmaceutically acceptable salt thereof.  
 
 
     
     
         2 . A quinazoline derivative of the Formula I according to  claim 1  wherein each of R 1 , G 1 , G 2 , X 1  and X 2  has any of the meanings defined in  claim 1;  and 
 Q 1  is a non-aromatic saturated or partially saturated 3 to 7 membered monocyclic heterocyclyl ring with 1 ring nitrogen heteroatom and optionally 1 or 2 heteroatoms selected from nitrogen and sulfur, which ring is linked to the group X 2 —O— by a ring carbon atom, and wherein Q 1  optionally bears 1, 2 or 3 substituents, which may be the same or different, selected from halogeno, trifluoromethyl, trifluoromethoxy, cyano, nitro, hydroxy, amino, carbamoyl, acryloyl, (1-6C)alkyl, (2-8C)alkenyl, (2-8C)alkynyl, (1-6C)alkoxy, (2-6C)alkenyloxy, (2-6C)alkynyloxy, (1-6C)alkylthio, (2-6C)alkenylthio, (2-6C)alkynylthio, (1-6C)alkylsulfinyl, (2-6C)alkenylsulfinyl, (2-6C)alkynylsulfinyl, (1-6C)alkylsulfonyl, (2-6C)alkenylsulfonyl, (2-6C)alkynylsulfonyl, (1-6C)alkylamino, di-[(1-6C)alkyl]amino,  N -(1-6C)alkylcarbamoyl,  N , N -di-[(1-6)alkyl]carbamoyl, (2-6C)alkanoyl, (2-6C)alkanoylamino,  N -(1-6C)alkyl-(2-6C)alkanoylamino, sulfamoyl,  N -(1-6C)alkylsulfamoyl,  N , N -di-[(1-6C)alkyl]sulfamoyl, (1-6C)alkanesulfonylamino,  N -(1-6C)alkyl-(1-6C)alkanesulfonylamino, carbamoyl(1-6C)alkyl,  N -(1-6C)alkylcarbamoyl(1-6C)alkyl,  N , N -di-[(1-6C)alkyl]carbamoyl(1-6C)alkyl, sulfamoyl(1-6C)alkyl,  N -(1-6C)alkylsulfamoyl(1-6C)alkyl,  N , N -di-[(1-6C)alkyl]sulfamoyl(1-6C)alkyl, (2-6C)alkanoyl(1-6C)alkyl, (2-6C)alkanoyloxy(1-6C)alkyl, (2-6C)alkanoylamino(1-6C)alkyl and  N -(1-6C)alkyl-(2-6C)alkanoylamino(1-6C)alkyl, or from a group of the formula:      Q 2 -X 3 —   wherein X 3  is CO and Q 2  is a heterocyclyl group selected from morpholino and a 4, 5 or 6-membered monocyclic heterocyclyl group containing 1 nitrogen heteroatom and optionally 1 or 2 heteroatoms selected from sulfur and nitrogen,    and wherein Q 2  optionally bears 1 or 2 substituents, which may be the same or different, selected from halogeno, hydroxy, (1-4C)alkyl, (2-4C)alkanoyl and (1-4C)alkylsulfonyl,    and wherein any (1-6C)alkyl, (2-8C)alkenyl, (2-8C)alkynyl and (2-6C)alkanoyl group within Q 1  optionally bears one or more substituents, which may be the same or different, selected from halogeno, hydroxy and (1-6C)alkyl and/or optionally a substituent selected from cyano, nitro, (2-8C)alkenyl, (2-8C)alkynyl, (1-6C)alkoxy, hydroxy(1-6C)alkoxy, (1-4C)alkoxy(1-6C)alkoxy, (2-6C)alkanoyl, (2-6C)alkanoyloxy and NR a R b , wherein R a  is hydrogen or (1-4C)alkyl and R b  is hydrogen or (1-4C)alkyl, and wherein any (1-4C)alkyl in R a  or R b  optionally bears one or more substituents, which may be the same or different, selected from halogeno and hydroxy and/or optionally a substituent selected from cyano, nitro, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)alkoxy, hydroxy(1-4C)alkoxy and (1-2C)alkoxy(1-4C)alkoxy,    or R a  and R b  together with the nitrogen atom to which they are attached form a 4, 5 or 6 membered ring, which optionally bears 1 or 2 substituents, which may be the same or different, on an available ring carbon atom selected from halogeno, hydroxy, (1-4C)alkyl and (1-3C)alkylenedioxy, and may optionally bear on any available ring nitrogen a substituent (provided the ring is not thereby quaternised) selected from (1-4C)alkyl, (2-4C)alkanoyl and (1-4C)alkylsulfonyl,    wherein any (1-4C)alkyl or (2-4C)alkanoyl group present as a substituent on the ring formed by R a  and R b  together with the nitrogen atom to which they are attached optionally bears one or more substituents, which may be the same or different, selected from halogeno and hydroxy and/or optionally a substituent selected from (1-4C)alkyl and (1-4C)alkoxy;    and wherein any heterocyclyl group within the Q 1 -X 2 — group optionally bears 1 or 2 oxo (═O) or thioxo (═S) substituents;    provided that when X 2  is [CH 2 ] m , m is an integer from 1 to 6, and Q 1  is a pyrrolidinyl or piperidinyl group substituted at the 1-position by a (2-4C)alkyl or (2-5C)alkanoyl group, then the (2-4C)alkyl or (2-5C)alkanoyl group at the 1-position on Q 1  is not substituted by a 2-oxo-morpholino group.    
     
     
         3 . A quinazoline derivative of the Formula I according to  claim 1  wherein each of R 1 , G 1 , G 2 , X 1  and X 2  has any of the meanings defined in  claim 1;  and 
 Q 1  is (3-7C)cycloalkyl or heterocyclyl, wherein Q 1  optionally bears 1, 2 or 3 substituents, which may be the same or different, selected from halogeno, trifluoromethyl, trifluoromethoxy, cyano, nitro, hydroxy, amino, carboxy, carbamoyl, (1-6C)alkyl, (2-8C)alkenyl, (2-8C)alkynyl, (1-6C)alkoxy, (2-6C)alkenyloxy, (2-6C)alkynyloxy, (1-6C)alkylthio, (1-6C)alkylsulfinyl, (1-6C)alkylsulfonyl, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, (1-6C)alkoxycarbonyl,  N -(1-6C)alkylcarbamoyl,  N , N -di-[(1-6C)alkyl]carbamoyl, (2-6C)alkanoyl, (2-6C)alkanoyloxy, (2-6C)alkanoylamino,  N -(1-6C)alkyl-(2-6C)alkanoylamino, sulfamoyl,  N -(1-6C)alkylsulfamoyl,  N , N -di-[(1-6C)alkyl]sulfamoyl, (1-6C)alkanesulfonylamino,  N -(1-6C)alkyl-(1-6C)alkanesulfonylamino, carbamoyl(1-6C)alkyl,  N -(1-6C)alkylcarbamoyl(1-6C)alkyl,  N , N -di-[(1-6C)alkyl]carbamoyl(1-6C)alkyl, (2-6C)alkanoyl(1-6C)alkyl, (2-6C)alkanoyloxy(1-6C)alkyl, (2-6C)alkanoylamino(1-6C)alkyl,  N -(1-6C)alkyl-(2-6C)alkanoylamino(1-6C)alkyl and (1-6C)alkoxycarbonyl(1-6C)alkyl,    and wherein any (1-6C)alkyl, (2-8C)alkenyl, (2-8C)alkynyl and (2-6C)alkanoyl group within Q 1  optionally bears one or more substituents, which may be the same or different, selected from halogeno, hydroxy and (1-6C)alkyl and/or optionally a substituent selected from cyano, nitro, carboxy, (2-8C)alkenyl, (2-8C)alkynyl, (1-6C)alkoxy, hydroxy(1-6C)alkoxy and NR a R b , wherein R a  is hydrogen or (1-4C)alkyl and R b  is hydrogen or (1-4C)alkyl,    or R a  and R b  together with the nitrogen atom to which they are attached form a 4, 5 or 6 membered ring;    and wherein any heterocyclyl group within the Q 1 -X 2 — group optionally bears 1 or 2 oxo (═O) or thioxo (═S) substituents;    
     
     
         4 . A quinazoline derivative of the Formula I according to  claim 1  wherein each of R 1 , G 1 , G 2 , X 1  and X 2  has any of the meanings defined in  claim 1;  and 
 Q 1  is a non-aromatic saturated or partially saturated 4, 5 or 6 membered monocyclic heterocyclyl ring with 1 or 2 ring nitrogen heteroatom(s), which ring is linked to the group X 2 —O— by a ring carbon atom, and wherein Q 1  optionally bears 1 or 2 substituents, which may be the same or different, selected from halogeno, cyano, nitro, hydroxy, carbamoyl, acryloyl, (1-6C)alkyl, (1-6C)alkylthio, (2-6C)alkenylthio, (2-6C)alkynylthio, (1-6C)alkylsulfinyl, (2-6C)alkenylsulfinyl, (2-6C)alkynylsulfinyl, (1-6C)alkylsulfonyl, (2-6C)alkenylsulfonyl, (2-6C)alkynylsulfonyl,  N -(1-6C)alkylcarbamoyl,  N , N -di-[(1-6C)alkyl]carbamoyl, (2-6C)alkanoyl, sulfamoyl,  N -(1-6C)alkylsulfamoyl,  N , N -di-[(1-6C)alkyl]sulfamoyl, carbamoyl(1-6C)alkyl,  N -(1-6C)alkylcarbamoyl(1-6C)alkyl,  N , N -di-[(1-6C)alkyl]carbamoyl(1-6C)alkyl, sulfamoyl(1-6C)alkyl,  N -(1-6C)alkylsulfamoyl(1-6C)alkyl,  N , N -di-[(1-6C)alkyl]sulfamoyl(1-6C)alkyl, (2-6C)alkanoyl(1-6C)alkyl, (2-6C)alkanoyloxy(1-6C)alkyl, (2-6C)alkanoylamino(1-6C)alkyl and  N -(1-6C)alkyl-(2-6C)alkanoylamino(1-6C)alkyl, or from a group of the formula:      Q 2 -X 3 —   wherein X 3  is CO and Q 2  is a heterocyclyl group selected from morpholino, piperidinyl, piperazinyl and pyrrolidinyl    and wherein Q 2  optionally bears 1 or 2 substituents, which may be the same or different, selected from halogeno, hydroxy, (1-4C)alkyl, (2-4C)alkanoyl and (1-4C)alkylsulfonyl,    and wherein any (1-6C)alkyl, or (2-6C)alkanoyl group within Q 1  optionally bears 1 or 2 substituents, which may be the same or different, selected from halogeno, hydroxy and (1-6C)alkyl and/or optionally a substituent selected from cyano, (2-8C)alkenyl, (2-8C)alkynyl, (1-6C)alkoxy, (2-6C)alkanoyl, (2-6C)alkanoyloxy and NR a R b , wherein R a  is hydrogen or (1-4C)alkyl and R b  is hydrogen or (1-4C)alkyl, and wherein any (1-4C)alkyl in R a  or R b  optionally bears one or more substituents, which may be the same or different, selected from halogeno and hydroxy and/or optionally a substituent selected from cyano, and (1-4C)alkoxy,    or R a  and R b  together with the nitrogen atom to which they are attached form a 4, 5 or 6 membered ring which does not contain oxygen, which ring optionally bears 1 or 2 substituents, which may be the same or different, on an available ring carbon atom selected from halogeno, hydroxy, (1-4C)alkyl and (1-3C)alkylenedioxy, and may optionally bear on any available ring nitrogen a substituent (provided the ring is not thereby quaternised) selected from (1-4C)alkyl, (2-4C)alkanoyl and (1-4C)alkylsulfonyl,    and wherein any (1-4C)alkyl or (2-4C)alkanoyl group present as a substituent on the ring formed by R a  and R b  together with the nitrogen atom to which they are attached optionally bears one or more substituents, which may be the same or different, selected from halogeno and hydroxy and/or optionally a substituent selected from (1-4C)alkyl and (1-4C)alkoxy;    and wherein any heterocyclyl group within the Q 1 -X 2 — group optionally bears 1 or 2 oxo (═O) or thioxo (═S) substituents.    
     
     
         5 . A quinazoline derivative of the Formula I according to  claim 1  wherein each of R 1 , G 1 , G 2 , X 1  and X 2  has any of the meanings defined in  claim 1;  and 
 Q 1  is selected from pyrrolidinyl and piperidinyl linked to the group X 2 —O— by a ring carbon atom and wherein the pyrrolidinyl or piperidinyl group is optionally substituted by 1 or 2 groups selected from halogeno, cyano, hydroxy, carbamoyl, (1-6C)alkyl, (1-6C)alkylthio, (1-6C)alkylsulfinyl, (1-6C)alkylsulfonyl,  N -(1-6C)alkylcarbamoyl,  N , N -di-[(1-6C)alkyl]carbamoyl, (2-6C)alkanoyl, sulfamoyl,  N -(1-6C)alkylsulfamoyl,  N , N -di-[(1-6C)alkyl]sulfamoyl, carbamoyl(1-6C)alkyl,  N -(1-6C)alkylcarbamoyl(1-6C)alkyl,  N , N -di-[(1-6C)alkyl]carbamoyl(1-6C)alkyl, sulfamoyl(1-6C)alkyl,  N -(1-6C)alkylsulfamoyl(1-6C)alkyl,  N , N -di-[(1-6C)alkyl]sulfamoyl(1-6C)alkyl and (2-6C)alkanoyl(1-6C)alkyl, or from a group of the formula:      Q 2 -X 3 —   wherein X 3  is CO and Q 2  is a heterocyclyl group selected from morpholino, piperidino, piperazin-1-yl, pyrrolidin-1-yl and pyrrolidin-2-yl,    and wherein Q 2  optionally bears 1 or 2 substituents, which may be the same or different, selected from halogeno, hydroxy, (1-4C)alkyl, (2-4C)alkanoyl and (1-4C)alkylsulfonyl,    and wherein any (1-6C)alkyl, or (2-6C)alkanoyl group within Q 1  optionally bears 1 or 2 substituents, which may be the same or different, selected from halogeno, hydroxy and (1-6C)alkyl and/or optionally a a substituent selected from cyano, (2-8C)alkenyl, (2-8C)alkynyl, (1-6C)alkoxy, (2-6C)alkanoyl, (2-6C)alkanoyloxy and NR a R b , wherein R a  is hydrogen or (1-4C)alkyl and R b  is hydrogen or (1-4C)alkyl, and wherein any (1-4C)alkyl in R a  or R b  optionally bears one or more substituents, which may be the same or different, selected from halogeno and hydroxy and/or optionally a substituent selected from cyano, and (1-4C)alkoxy,    or R a  and R b  together with the nitrogen atom to which they are attached form a ring selected from pyrrolidin-1-yl, piperidino and piperazin-1-yl, which ring optionally bears 1 or 2 substituents, which may be the same or different, on an available ring carbon atom selected from halogeno, hydroxy, (1-4C)alkyl and methylenedioxy, and may optionally bear on any available ring nitrogen a substituent (provided the ring is not thereby quaternised) selected from (1-4C)alkyl, (2-4C)alkanoyl and (1-4C)alkylsulfonyl,    and wherein any (1-4C)alkyl or (2-4C)alkanoyl group present as a substituent on the ring formed by R a  and R b  together with the nitrogen atom to which they are attached optionally bears one or more substituents, which may be the same or different, selected from halogeno and hydroxy and/or optionally a substituent selected from (1-4C)alkyl and (1-4C)alkoxy;    and wherein any heterocyclyl group within the Q 1 -X 2 — group optionally bears 1 or 2 oxo (═O) substituents.    
     
     
         6 . A quinazoline derivative of the Formula I according to any one of the preceding claims wherein X 2  is a direct bond or CH 2 .  
     
     
         7 . A quinazoline derivative of the Formula I according to  claim 1  wherein each of R 1 , G 1 , G 2  and X 1  has any of the meanings defined in  claim 1;  and 
 Q 1 -X 2  is selected from pyrrolidin-2-ylmethyl, pyrrolidin-3-yl, pyrrolidin-3-ylmethyl, piperidin-4-yl, piperidin-4-ylmethyl and piperidin-3-yl wherein Q 1  is substituted by 1 or 2 groups, which may be the same or different, selected from carbamoyl, (1-4C)alkyl, (1-4C)alkylsulfonyl,  N -(1-4C)alkylcarbamoyl,  N , N -di-[(1-4C)alkyl]carbamoyl, (2-4C)alkanoyl, sulfamoyl,  N -(1-4C)alkylsulfamoyl,  N , N -di-[(1-4C)alkyl]sulfamoyl, carbamoyl(1-3C)alkyl,  N -(1-4C)alkylcarbamoyl(1-3C)alkyl,  N , N -di-[(1-4C)alkyl]carbamoyl(1-3C)alkyl, (2-4C)alkanoyl(1-3C)alkyl, amino(2-4C)alkanoyl, (1-4C)alkylamino-(2-4C)alkanoyl,  N , N -di-[(1-4C)alkyl]amino-(2-4C)alkanoyl, (2-4C)alkanoyloxy-(2-4C)alkanoyl, amino(1-3C)alkylsulfonyl,  N -(1-4C)alkylamino-(1-3C)alkylsulfonyl,  N , N -di[(1-4)alkyl]amino(1-3C)alkylsulfonyl, pyrrolidin-1-yl-(2-4C)alkanoyl, 3,4-methylenedioxypyrrolidin-1-yl-(2-4C)alkanoyl, piperidino-(2-4C)alkanoyl, piperazin-1-yl-(2-4C)alkanoyl, morpholino-(2-4C)alkanoyl and a group of the formula:      Q 2 -X 3 —   wherein X 3  is CO and Q 2  is selected from pyrrolidin-1-yl, pyrrolidin-2-yl, morpholino and piperidino,    and wherein any pyrrolidin-1-yl, pyrrolidin-2-yl, morpholino, piperidino or piperazin-1-yl group within a substituent on Q 1  or which is represented by Q 2  optionally bears one or two substituents, which may be the same or different, selected from hydroxy, (1-4C)alkyl, (2-4C)alkanoyl and halogeno,    and wherein any (2-4C)alkanoyl group in a substituent on Q 1  optionally bears one or two substituents, which may be the same or different, selected from hydroxy and (1-3C)alkyl,    and wherein any (1-4C)alkyl group in a substituent on Q 1  optionally bears one or two substituents, which may be the same or different, selected from hydroxy, (1-4C)alkoxy and halogeno,    and wherein any heterocyclyl group within the Q 1 -X 2 — group optionally bears an oxo (═O) substituent.    
     
     
         8 . A quinazoline derivative of the Formula I according to  claim 1  wherein each of R 1 , G 1 , G 2  and X 1  has any of the meanings defined in  claim 1;  and 
 Q 1 -X 2  is selected from pyrrolidin-3-yl, piperidin-4-yl and piperidin-3-yl, wherein Q 1  is substituted at the 1-position by a group selected from (1-4C)alkyl, (1-4C)alkylsulfonyl, (2-4C)alkanoyl, (2-4C)alkanoyl(1-3C)alkyl, amino(2-4C)alkanoyl, (1-4C)alkylamino-(2-4C)alkanoyl,  N , N -di-[(1-4C)alkylamino-(2-4C)alkanoyl, (2-4C)alkanoyloxy-(2-4C)alkanoyl, amino(1-3C)alkylsulfonyl,  N -(1-4C)alkylamino-(1-3C)alkylsulfonyl,  N , N -di[(1-4)alkyl]amino(1-3C)alkylsulfonyl, pyrrolidin-1-yl-(2-4C)alkanoyl, 3,4-methylenedioxypyrrolidin-1-yl-(2-4C)alkanoyl, piperidino-(2-4C)alkanoyl, piperazin-1-yl-(2-4C)alkanoyl, morpholino-(2-4C)alkanoyl and a group of the formula:      Q 2 -X 3 —   wherein X 3  is CO and Q 2  is pyrrolidin-2-yl,    and wherein any pyrrolidin-1-yl, pyrrolidin-2-yl, morpholino, piperidino or piperazin-1-yl group within a substituent on Q 1  or which is represented by Q 2  optionally bears one or two substituents, which may be the same or different, selected from hydroxy, (1-4C)alkyl, (2-4C)alkanoyl and halogeno,    and wherein any (2-4C)alkanoyl group in a substituent on Q 1  optionally bears one or two substituents, which may be the same or different, selected from hydroxy and (1-3C)alkyl,    and wherein any (1-4C)alkyl group in a substituent on Q 1  optionally bears one or two substituents, which may be the same or different, selected from hydroxy, (1-4C)alkoxy and halogeno,    and wherein any heterocyclyl group within the Q 1 -X 2 — group optionally bears an oxo (═O) substituent.    
     
     
         9 . A quinazoline derivative of the Formula I according to  claim 1  wherein each of R 1 , G 1 , G 2  and X 1  has any of the meanings defined in  claim 1;  and 
 Q 1 -X 2  is a group of the formula A:                          R 4  is selected from carbamoyl,  N -(1-6C)alkylcarbamoyl,  N , N -di-[(1-6C)alkyl]carbamoyl and a group of the formula:      Q 2 -X 3 —   wherein X 3  is CO and Q 2  is a heterocyclyl group selected from a 4, 5 or 6-membered monocyclic heterocyclyl group containing 1 nitrogen heteroatom and optionally 1 or 2 heteroatoms selected from sulfur, oxygen and nitrogen,    and wherein Q 2  is attached to X 3  by a ring nitrogen atom,    and wherein Q 2  optionally bears one or more substituents, which may be the same or different, selected from halogeno, hydroxy, (1-4C)alkyl and (2-4C)alkanoyl,    and wherein any (1-6C)alkyl or (2-6C)alkanoyl group within R 4  optionally bears one or more substituents, which may be the same or different, selected from halogeno, hydroxy and (1-6C)alkyl and/or optionally a substituent selected from cyano, nitro, (2-8C)alkenyl, (2-8C)alkynyl and (1-6C)alkoxy,    R 5  is selected from hydrogen, (1-6C)alkyl, (1-6C)alkylthio, (1-6C)alkylsulfinyl, (1-6C)alkylsulfonyl, (2-6C)alkanoyl, carbamoyl(1-6C)alkyl,  N -(1-6C)alkylcarbamoyl(1-6C)alkyl,  N , N -di-[(1-6C)alkyl]carbamoyl(1-6C)alkyl, sulfamoyl(1-6C)alkyl,  N -(1-6C)alkylsulfamoyl(1-6C)alkyl,  N , N -di-[(1-6C)alkyl]sulfamoyl(1-6C)alkyl and (2-6C)alkanoyl(1-6C)alkyl,    and wherein any (1-6C)alkyl or (2-6C)alkanoyl group within R 5  optionally bears one or more substituents, which may be the same or different, selected from halogeno, hydroxy and (1-6C)alkyl and/or optionally a substituent selected from cyano, nitro, (2-8C)alkenyl, (2-8C)alkynyl, (1-6C)alkoxy and NR a R b , wherein R 1  is hydrogen or (1-4C)alkyl and R b  is hydrogen or (1-4C)alkyl, and wherein any (1-4C)alkyl in R a  or R b  optionally bears one or more substituents, which may be the same or different, selected from halogeno and hydroxy and/or optionally a substituent selected from cyano, nitro and (1-4C)alkoxy,    or R a  and R b  together with the nitrogen atom to which they are attached form a 4, 5 or 6 membered ring, which optionally bears 1 or 2 substituents, which may be the same or different, on an available ring carbon atom selected from halogeno, hydroxy, (1-4C)alkyl and (1-3C)alkylenedioxy, and may optionally bear on any available ring nitrogen a substituent (provided the ring is not thereby quaternised) selected from (1-4C)alkyl and (2-4C)alkanoyl,    and wherein any (1-4C)alkyl or (2-4C)alkanoyl group present as a substituent on the ring formed by R a  and R b  together with the nitrogen atom to which they are attached optionally bears one or more substituents, which may be the same or different, selected from halogeno and hydroxy and/or optionally a substituent selected from (1-4C)alkyl and (1-4C)alkoxy,    and wherein any heterocyclyl group within the Q 1 -X 2 — group optionally bears 1 or 2 oxo (═O) or thioxo (═S) substituents.    
     
     
         10 . A quinazoline derivative of the Formula I according to  claim 1  wherein each of R 1 , G 1 , G 2  and X 1  has any of the meanings defined in  claim 1;  and 
 Q 1 -X 2  is a group of the formula A:                          R 4  is selected from  N , N -di-[(1-4C)alkyl]carbamoyl and a group of the formula:      Q 2 -X 3 —   wherein X 3  is CO and Q 2  is selected from pyrrolidin-1-yl, morpholino and piperidino,    and wherein Q 2  optionally bears 1 or 2 substituents, which may be the same or different, selected from fluoro, chloro, hydroxy, methyl and oxo,    and wherein any (1-4C)alkyl group within R 4  optionally bears 1 or 2 substituents, which may be the same or different, selected from fluoro, chloro and hydroxy and/or optionally a substituent selected from methoxy,    R 5  is selected from hydrogen, methyl, ethyl, isopropyl, isobutyl and cycloproplymethyl,    and wherein any (1-4C)alkyl group within R 5  optionally bears 1 or 2 substituents, which may be the same or different, selected from fluoro, chloro and hydroxy, and/or optionally a substituent selected from methoxy.    
     
     
         11 . A quinazoline derivative of the Formula I according to any one of the preceding claims wherein R 1 —X 1  is selected from hydrogen, (1-6C)alkoxy and (1-4C)alkoxy(1-6C)alkoxy, and wherein any (1-6C)alkoxy group within R 1 X 1  optionally bears 1, 2 or 3 substituents, which may be the same or different, selected from hydroxy, fluoro and chloro.  
     
     
         12 . A quinazoline derivative of the Formula I according to any one of the preceding claims wherein G 1  is fluoro and G 2  is chloro.  
     
     
         13 . A quinazoline derivative of the Formula I according to any one of the preceding claims wherein R 1 —X 1  is selected from hydrogen and (1-4C)alkoxy.  
     
     
         14 . A quinazoline derivative of the Formula:  
       
         
           
           
               
               
           
         
         R 1 —X 1  is (1-4C)alkoxy;  
         Q 1 -X 2  is a group of the formula A:  
         
           
             
             
                 
                 
             
           
         
         R 4  is N,N-dimethylcarbamoyl or morpholinocarbonyl;  
         R 5  is hydrogen or methyl;  
         G 1  is fluoro; and  
         G 2  is chloro;  
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         15 . A quinazoline derivative of the Formula I according to  claim 1  selected from: 
 4-(3-Chloro-2-fluoroanilino)-6-{[1-(methylsulfonyl)piperidin-4-yl]oxy}-7-methoxyquinazoline; and    6-{[1-(carbamoylmethyl)piperidin-4-yl]oxy}-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline;    or a pharmaceutically acceptable acid addition salt thereof.    
     
     
         16 . A quinazoline derivative of the Formula I according to  claim 1  selected from: 
 4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-[(1-methylpyrrolidin-3-yl)oxy]quinazoline;    4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-[(piperidin-4-yl)oxy]quinazoline;    4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-[(piperidin-4-yl)methoxy]quinazoline;    4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-[(1-methylpiperidin-4-yl)oxy]quinazoline;    4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-[(1-methylpiperidin-4-yl)methoxy]quinazoline;    4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-[2-(1-methylpiperidin-4-yl)ethoxy]quinazoline;    4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-{[1-(2-methoxyethyl)piperidin-4-yl]oxy}quinazoline;    4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-{[1-(2-methoxyethyl)piperidin-4-yl]methoxy}quinazoline;    4-(3-Chloro-2-fluoroanilino)-6-1 [1-(methylsulfonyl)piperidin-4-yl]methoxy]-7-methoxyquinazoline,    6-{[1-(carbamoylmethyl)piperidin-4-yl]methoxy}4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline;    4-(3-Chloro-2-fluoroanilino)-6-{[1-(cyanomethyl)piperidin-4-yl]oxy}-7-methoxyquinazoline;    4-(3-Chloro-2-fluoroanilino)-6-{[1-(cyanomethyl)piperidin-4-yl]methoxy}-7-methoxyquinazoline;    4-(3-Chloro-2-fluoroanilino)-6-[(1-cyanopiperidin-4-yl)methoxy]-7-methoxyquinazoline;    6-(1-acetylpiperidin-4-yloxy)-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-6-[1-(N,N-dimethylaminoacetyl)piperidin-4-yloxy]-7-methoxyquinazoline;    6-[1-(N,N-dimethylsulfamoyl)piperidin-4-yloxy]-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[1-(morpholinoacetyl)piperidin-4-yloxy]quinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[1-(pyrrolidin-4-ylacetyl)piperidin-4-yloxy]quinazoline;    4-(3-chloro-2-fluoroanilino)-6-{1-[3-(dimethylamino)propylsulfonyl]piperidin-4-yloxy}-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-6-[1-(methylsulfonyl)piperidin-3-yl]oxy]-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-6-[(3R)-1-(methylsulfonyl)piperidin-3-yloxy]-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-6-[(3S)-1-(methylsulfonyl)piperidin-3-yloxy]-7-methoxyquinazoline;    6-(1-acetylpiperidin-3-yloxy)-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-6-[(2S,4S)-2-(N,N-dimethylcarbamoyl)pyrrolidin-4-yloxy]-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-6-[(2S,4S)-2-(N,N-dimethylcarbamoyl)-1-methylpyrrolidin-4-yloxy]-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-6-[1-(N,N-dimethylaminoacetyl)piperidin-3-yloxy]-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-6-[(3R)-1-( N , N -dimethylaminoacetyl)piperidin-3-yloxy]-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-6-[(3S)-1-(N,N-dimethylaminoacetyl)piperidin-3-yloxy]-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-6-[1-(hydroxyacetyl)piperidin-3-yloxy]-7-methoxyquinazoline;    6-[1-(acetoxyacetyl)piperidin-3-yloxy]-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-6-[(3R)-1-(methylsulfonyl)pyrrolidin-3-yloxy]-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-6-[(3S)-1-(methylsulfonyl)pyrrolidin-3-yloxy]-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-methylsulfonylpyrrolidin-2-yl]methoxy}quinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2R)-1-methylsulfonylpyrrolidin-2-yl]methoxy}quinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[1-(methylsulfonyl)pyrrolidin-3-yl]methoxy}quinazoline;    4-(3-chloro-2-fluoroanilino)-6-[(3R)-1-methylpyrrolidin-3-yloxy]-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-6-[(3S)-1-methylpyrrolidin-3-yloxy]-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-methylpyrrolidin-2-yl]methoxy}quinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[(1-methylpyrrolidin-3-yl)methoxy]quinazoline;    6-[(3R)-1-acetylpyrrolidin-3-yloxy]4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline;    6-([(2S)-1-acetylpyrrolidin-2-yl]methoxy)-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline;    6-{[(2R)-1-acetylpyrrolidin-2-yl]methoxy}-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline;    6-[(1-acetylpyrrolidin-3-yl)methoxy]-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[(3S)-1-( N , N -dimethylsulfamoyl)pyrrolidin-3-yloxy]quinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{1[(2S)-1-(morpholinoacetyl)pyrrolidin-2-yl]methoxy}quinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(hydroxyacetyl)pyrrolidin-2-yl]methoxy}quinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-3-yloxy)quinazoline;    4-(3-chloro-2-fluoroanilino)-6-[(2S,4R)-2-(N,N-dimethylcarbamoyl)-1-methylpyrrolidin-4-yloxy]-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-6-[(2R,4R)-2-(N,N-dimethylcarbamoyl)-1-methylpyrrolidin-2-yloxy]-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(N-methylaminoacetyl)pyrrolidin-2-yl]methoxy}quinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(N,N-dimethylaminoacetyl)pyrrolidin-2-yl]methoxy}quinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(pyrrolidin-1-ylacetyl)pyrrolidin-2-yl]methoxy}quinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[(2RS,4R)-1-methyl-2-(morpholinocarbonyl)-pyrrolidin-4-yloxy]quinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[(3S)-piperidin-3-yloxy]quinazoline;    6-[(3S)-1-acetylpiperidin-3-yloxy]4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[(3S)-1-(methylsulfonyl)piperidin-3-yloxy]quinazoline;    4-(3-chloro-2-fluoroanilino)-6-{(3S)-1-[(dimethylamino)acetyl]piperidin-3-yloxy}-7-methoxyquinazoline; 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[1-(pyrrolidin-1-ylacetyl)piperidin-3-yloxy]quinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[(3S)-1-(pyrrolidin-1-ylacetyl)piperidin-3-yloxy]quinazoline;    4-(3-chloro-2-fluoroanilino)-6-{[(2S)-1-(3,4-methylenedioxypyrrolidin-1-ylacetyl)pyrrolidin-2-yl]methoxy}-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(1-methylpiperazin-4-ylacetyl)pyrrolidin-2-yl]methoxy}quinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(1-methylpiperazin-4-ylacetyl)pyrrolidin-2-yl]methoxy}quinazoline;    4-(3-chloro-2-fluoroanilino)-6-[(3R)-1-(hydroxyacetyl)pyrrolidin-3-yloxy]-7-methoxyquinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-1-(2-hydroxyisobutyryl)pyrrolidin-2-yl]methoxy}quinazoline;    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{1-[(2S)-1-methylpyrrolidin-2-ylcarbonyl]piperidin-3-yloxy}quinazoline;    4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-[1-(N,N-dimethylcarbamoylmethyl)piperidin-3-yloxy]quinazoline;    4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-[1-(3,3-difluoropyrolidin-1-ylacetyl)piperidin-3-yloxy]quinazoline;    4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-{1-[[(3R)-3-hydroxypyrrolidin-1-yl]acetyl]piperidin-3-yloxy}quinazoline;    4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-{[1-(4-methyl-3-oxopiperazin-1-yl)acetyl]piperidin-3-yloxy}quinazoline;    4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-{1-[(4-acetylpiperazin-1-yl)acetyl]piperidin-3-yloxy}quinazoline; and    4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2R)-1-methylpyrrolidin-2-yl]methoxy}quinazoline;    or a pharmaceutically acceptable salt thereof.    
     
     
         17 . A process for the preparation of a quinazoline derivative of the Formula I as defined in  claim 1  which comprises: 
 process (a) the reaction of a compound of the Formula II:                          wherein R 1 , X 1 , G 1  and G 2  have any of the meanings defined in  claim 1  except that any functional group is protected if necessary, with a compound of the Formula III:      Q 1 -X 2 -Lg  Formula III    wherein Q 1  and X 2  have any of the meanings defined in  claim 1  except that any functional group is protected if necessary and Lg is a displaceable group,    and whereafter any protecting group that is present is removed by conventional means; or    process (b) modifying a substituent in or introducing a substituent into another quinazoline derivative of Formula I or a pharmaceutically acceptable salt thereof, as defined in  claim 1  except that any functional group is protected if necessary,    and whereafter any protecting group that is present is removed by conventional means; or    process (c) the reaction of a compound of the Formula II as defined in process (a) with a compound of the formula Q 1 -X 2 —OH under Mitsunobu conditions, wherein Q 1  and X 2  have any of the meanings defined in  claim 1  except that any functional group is protected if necessary, and whereafter any protecting group that is present is removed by conventional means; or    process (d) for the preparation of a compound of the Formula I wherein R 1 —X 1  is a hydroxy group, the cleavage of a quinazoline derivative of the Formula I wherein R 1 —X 1  is a (1-6C)alkoxy group; or    Process (e) for the preparation of a compound of the Formula I wherein X 1  is O, the reaction of a compound of the Formula I wherein R 1 —X 1  is OH and Q 1 , X 2 , G 1  and G 2  have any of the meanings defined in  claim 1  except that any functional group is protected if necessary, with a compound of the formula R 1 -Lg, wherein R 1  has any of the meanings defined in  claim 1  except that any functional group is protected if necessary and Lg is a displaceable group, and whereafter any protecting group that is present is removed by conventional means; or    process (f) for the preparation of a compound of the Formula I wherein Q 1  or R 1  contains a (1-6C)alkoxy or substituted (1-6C)alkoxy group or a (1-6C)alkylamino or substituted (1-6C)alkylamino group, the allylation of a quinazoline derivative of the Formula I wherein Q 1  or R 1  contains a hydroxy group or a primary or secondary amino group as appropriate; or    Process (g) for the preparation of a compound of the Formula I wherein R 1  is substituted by a group T, wherein T is selected from (1-6C)alkylamino, di-[(1-6C)alkyl]amino, (2-6C)alkanoylamino, (1-6C)alkylthio, (1-6C)alkylsulfinyl and (1-6C)alkylsulfonyl, the reaction of a compound of the formula V:                          wherein Q 1 , X 1 , X 2 , R 1 , G 1  and G 2  have any of the meanings defined in  claim 1  except that any functional group is protected if necessary and Lg is a displaceable group with a compound of the formula TH, T is as defined above except that any functional group is protected if necessary and whereafter any protecting group that is present is removed by conventional means; or    Process (h) by reacting a compound of the formula VI:                          wherein R 1 , X 1 , X 2 , Q 1  have any of the meanings defined in  claim 1  except that any functional group is protected if necessary and Lg is a displaceable group, with an aniline of the formula VII:                          wherein G 1  and G 2  have any of the meanings defined in  claim 1  except that any functional group is protected if necessary, and whereafter any protecting group that is present is removed by conventional means; or    Process (i) for the preparation of a compound of the Formula I wherein Q 1  carries a substituted carbamoyl group or a group Q 2 -X 3 —, wherein Q 2  is a nitrogen containing heterocyclyl group linked to X 3  by a ring nitrogen and X 3  is CO; the coupling of a compound of the Formula I, as defined in  claim 1 , except any functional group is protected if necessary, and wherein Q 1  carries a carboxy group, with a primary or secondary amine or a group of the formula Q 2 H, wherein Q 2 H is a heterocyclic group containing an NH group; and whereafter any protecting group that is present is removed by conventional means;    and when a pharmaceutically acceptable salt of a quinazoline derivative of the Formula I is required it may be obtained using a conventional procedure.    
     
     
         18 . A pharmaceutical composition which comprises a quinazoline derivative of the Formula I, or a pharmaceutically-acceptable salt thereof, as defined in  claim 1  in association with a pharmaceutically-acceptable diluent or carrier.  
     
     
         19 . A quinazoline derivative of the Formula I as defined in  claim 1 , or a pharmaceutically acceptable salt thereof, for use as a medicament.  
     
     
         20 . The use of a quinazoline derivative of the Formula I, or a pharmaceutically-acceptable salt thereof, as defined hereinbefore in the manufacture of a medicament for use in the production of an anti-proliferative effect in a warm-blooded animal.  
     
     
         21 . A method for producing an anti-proliferative effect in a warm-blooded animal in need of such treatment which comprises administering to said animal a quinazoline derivative of the Formula I, or a pharmaceutically acceptable salt thereof, as defined in  claim 1 .  
     
     
         22 . A compound of the formula B or a salt thereof:  
       
         
           
           
               
               
           
         
         wherein Y is hydrogen or a displaceable group; and  
         R 1 , X 1 , G 1  and G 2  are as defined in  claim 1.