Quinazoline Derivatives as Angiogenesis Inhibitors

Abstract

The present invention relates to compounds of the formula I: wherein: ring C is an 8, 9, 10, 12 or 13-membered bicyclic or tricyclic moiety which moiety may be saturated or unsaturated, which may be aromatic or non-aromatic, and which optionally may contain 1-3 heteroatoms selected independently from O, N and S; is —O— —NH— or —S—; is 0, 1, 2, 3, 4 or 5; is 0, 1, 2 or 3; and R2 and R1 are as defined herein; and salts thereof; their use in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals; processes for the preparation of such compounds; pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof and methods of treating disease states involving angiogenesis by administering a compound of formula I or a pharmaceutically acceptable salt thereof. The compounds of formula I inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

1 . A compound of the formula I: 
       
         
           
           
               
               
           
         
         wherein: 
         ring C is an 8-, 9-, 10-, 12- or 13-membered bicyclic or tricyclic moiety which moiety may be saturated or unsaturated, which may be aromatic or non-aromatic, and which optionally may contain 1-3 heteroatoms selected independently from O, N and S; 
         Z is —O—, —NH— or —S—; 
         n is 0, 1, 2, 3, 4 or 5; 
         m is 0, 1, 2 or 3; 
         R 2  represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkylsulphanyl, —NR 3 R 4  (wherein R 3  and R 4 , which may be the same or different, each represents hydrogen or C 1-3 alkyl), or R 5 X 1 — (wherein X 1  represents a direct bond, —O—, —CH 2 —, —OC(O)—, —C(O)—, —S—, —SO—, —SO 2 —, —NR 6 C(O)—, —C(O)NR 7 —, —SO 2 NR 8 —, —NR 9 SO 2 — or —NR 10 — (wherein R 6 , R 7 , R 8 , R 9  and R 10  each independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl), and R 5  is selected from one of the following twenty-two groups:
 1) hydrogen, oxiranylC 1-4 alkyl or C 1-5 alkyl which may be unsubstituted or which may be substituted with one or more groups selected from hydroxy, fluoro, chloro, bromo and amino; 
 2) C 1-5 alkylX 2 C(O)R 11  (wherein X 2  represents —O— or —NR 12 — (in which R 12  represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) and R 11  represents C 1-3 alkyl, —NR 13 R 14  or —OR 5  (wherein R 13 , R 14  and R 15  which may be the same or different each represents hydrogen, C 1-5 alkyl or C 1-3 alkoxyC 2-3 alkyl)); 
 3) C 1-5 alkylX 3 R 16  (wherein X 3  represents —O—, —S—, —SO—, —SO 2 —, —OC(O)—, —NR 17 C(O)—, —C(O)NR 18 —, SO 2 NR 19 —, —NR 20 SO 2 — or —NR 21 — (wherein R 17 , R 18 , R 19 , R 20  and R 21  each independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) and R 16  represents hydrogen, C 1-3 alkyl, cyclopentyl, cyclohexyl or a 5-6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which C 1-3 alkyl group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno and C 1-4 alkoxy and which cyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, cyano, C 1-4 cyanoalkyl, C 1-4 alkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 alkoxyC 1-4 alkyl, C 1-4 alkylsulphonylC 1-4 alkyl, C 1-4 alkoxycarbonyl, C 1-4 aminoalkyl, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 alkylaminoC 1-4 alkyl, di(C 1-4 alkyl)aminoC 1-4 alkyl, C 1-4 alkylaminoC 1-4 alkoxy, di(C 1-4 alkyl)aminoC 1-4 alkoxy and a group —(—O—) f (C 1-4 alkyl) g ringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 5-6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which cyclic group may bear one or more substituents selected from C 1-4 alkyl)); 
 4) C 1-5 alkylX 4 C 1-5 alkylX 5 R 22  (wherein X 4  and X 5  which may be the same or different are each —O—, —S—, —SO—, —SO 2 —, —NR 23 C(O)—, —C(O)NR 24 —, —SO 2 NR 25 —, —NR 26 SO 2 — or —NR 27 — (wherein R 23 , R 24 , R 25 , R 26  and R 27  each independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) and R 22  represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl); 5) R 28  (wherein R 28  is a 5-6-membered saturated heterocyclic group (linked via carbon or nitrogen) with 1-2 heteroatoms, selected independently from O, S and N, which heterocyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, cyano, C 1-4 cyanoalkyl, C 1-4 alkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 alkoxyC 1-4 alkyl, C 1-4 alkylsulphonylC 1-4 alkyl, C 1-4 alkoxycarbonyl, C 1-4 aminoalkyl, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 alkylaminoC 1-4 alkyl, di(C 1-4 alkyl)aminoC 1-4 alkyl, C 1-4 alkylaminoC 1-4 alkoxy, di(C 1-4 alkyl)aminoC 1-4 alkoxy and a group —(—O—) f (C 1-4 alkyl) g ringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 5-6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which cyclic group may bear one or more substituents selected from C 1-4 alkyl)); 
 6) C 1-5 alkylR 28  (wherein R 28  is as defined herein); 
 7) C 2-5 alkenylR 28  (wherein R 28  is as defined herein); 
 8) C 2-5 alkynylR 28  (wherein R 28  is as defined herein); 
 9) R 29  (wherein R 29  represents a pyridone group, a phenyl group or a 5-6-membered aromatic heterocyclic group (linked via carbon or nitrogen) with 1-3 heteroatoms selected from O, N and S, which pyridone, phenyl or aromatic heterocyclic group may carry up to 5 substituents selected from oxo, hydroxy, halogeno, amino, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 hydroxyalkyl, C 1-4 aminoalkyl, C 1-4 alkylamino, C 1-4 hydroxyalkoxy, carboxy, trifluoromethyl, cyano, —C(O)NR 30 R 31 , —NR 32 C(O)R 33  (wherein R 30 , R 31 , R 32  and R 33 , which may be the same or different, each represents hydrogen, C 1-4 alkyl or C 1-3 alkoxyC 2-3 alkyl) and a group —(—O—) f (C 1-4 alkyl) g ringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 5-6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which cyclic group may bear one or more substituents selected from C 1-4 alkyl)); 
 10) C 1-5 alkylR 29  (wherein R 29  is as defined herein); 
 11) C 2-5 alkenylR 29  (wherein R 29  is as defined herein); 
 12) C 2-5 alkynylR 29  (wherein R 29  is as defined herein); 
 13) C 1-5 alkylX 6 R 29  (wherein X 6  represents —O—, —S—, —SO—, —SO 2 —, —NR 34 C(O)—, —C(O)NR 35 —, —SO 2 NR 36 —, —NR 37 SO 2 — or —NR 38 — (wherein R 34 , R 35 , R 36 , R 37  and R 38  each independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) and R 29  is as defined herein); 
 14) C 2-5 alkenylX 7 R 29  (wherein X 7  represents —O—, —S—, —SO—, —SO 2 —, —NR 39 C(O)—, —C(O)NR 40 —, —SO 2 NR 41 —, —NR 42 SO 2 — or —NR 43 — (wherein R 39 , R 40 , R 41 , R 42  and R 43  each independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) and R 29  is as defined herein); 
 15) C 2-5 alkynylX 8 R 29  (wherein X 8  represents —O—, —S—, —SO—, —SO 2 —, —NR 44 C(O)—, —C(O)NR 45 —, —SO 2 NR 46 —, —NR 47 SO 2 — or —NR 48 — (wherein R 44 , R 45 , R 46 , R 47  and R 48  each independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) and R 29  is as defined herein); 
 16) C 1-4 alkylX 9 C 1-4 alkylR 29  (wherein X 9  represents —O—, —S—, —SO—, —SO 2 —, —NR 49 C(O)—, —C(O)NR 50 —, —SO 2 NR 51 —, —NR 52 SO 2 — or —NR 53 — (wherein R 49 , R 50 , R 51 , R 52  and R 53  each independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) and R 29  is as defined herein); 
 17) C 1-4 alkylX 9 C 1-4 alkylR 28  (wherein X 9  and R 28  are as defined herein); 
 18) C 2-5 alkenyl which may be unsubstituted or which may be substituted with one or more groups selected from hydroxy, fluoro, amino, C 1-4 alkylamino,  N,N -di(C 1-4 alkyl)amino, aminosulphonyl,  N -C 1-4  alkylaminosulphonyl and  N,N -di(C 1-4 alkyl)aminosulphonyl; 
 19) C 2-5 alkynyl which may be unsubstituted or which may be substituted with one or more groups selected from hydroxy, fluoro, amino, C 1-4 alkylamino,  N,N -di(C 1-4 alkyl)amino, aminosulphonyl,  N -C 1-4  alkylaminosulphonyl and  N,N -di(C 1-4 alkyl)aminosulphonyl; 
 20) C 2-5 alkenylX 9 C 1-4 alkylR 28  (wherein X 9  and R 28  are as defined herein); 
 21) C 2-5 alkynylX 9 C 1-4 alkylR 28  (wherein X 9  and R 28  are as defined herein); and 
 22) C 1-4 alkylR 54 (C 1-4 alkyl) q (X 9 ) r R 55  (wherein X 9  is as defined herein, q is 0 or 1, r is 0 or 1, and R 54  and R 55  are each independently selected from hydrogen, C 1-3 alkyl, cyclopentyl, cyclohexyl and a 5-6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which C 1-3 alkyl group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno and C 1-4 alkoxy and which cyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, cyano, C 1-4 cyanoalkyl, C 1-4 alkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 alkoxyC 1-4 alkyl, C 1-4 alkylsulphonylC 1-4 alkyl, C 1-4 alkoxycarbonyl, C 1-4 aminoalkyl, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 alkylaminoC 1-4 alkyl, di(C 1-4 alkyl)aminoC 1-4 alkyl, C 1-4 alkylaminoC 1-4 alkoxy, di(C 1-4 alkyl)aminoC 1-4 alkoxy and a group —(—O—) f C 1-4 alkyl) g ringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 5-6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which cyclic group may bear one or more substituents selected from C 1-4 alkyl), with the proviso that R 54  cannot be hydrogen); 
 and additionally wherein any C 1-5 alkyl, C 2-5 alkenyl or C 2-5 alkynyl group in R 5 X 1 — which is linked to X 1  may bear one or more substituents selected from hydroxy, halogeno and amino); 
 R 1  represents hydrogen, oxo, halogeno, hydroxy, C 1-4 alkoxy, C 1-4 alkyl, C 1-4 alkoxymethyl, C 1-4 alkanoyl, C 1-4 haloalkyl, cyano, amino, C 2-5 alkenyl, C 2-5 alkynyl, C 1-3 alkanoyloxy, nitro, C 1-4 alkanoylamino, C 1-4 alkoxycarbonyl, C 1-4 alkylsulphanyl, C 1-4 alkylsulphinyl, C 1-4 alkylsulphonyl, carbamoyl,  N -C 1-4 alkylcarbamoyl,  N,N -di(C 1-4 alkyl)carbamoyl, aminosulphonyl,  N -C 1-4 alkylaminosulphonyl,  N,N -di(C 1-4 alkyl)aminosulphonyl,  N -(C 1-4 alkylsulphonyl)amino,  N -(C 1-4 alkylsulphonyl)- N -(C 1-4 alkyl)amino,  N,N -di(C 1-4 alkylsulphonyl)amino, a C 3-7 alkylene chain joined to two ring C carbon atoms, C 1-4 alkanoylaminoC 1-4 alkyl, carboxy or a group R 56 X 10  (wherein X 10  represents a direct bond, —O—, —CH 2 —, —OC(O)—, —C(O)—, —S—, —SO—, —SO 2 —, —NR 57 C(O)—, —C(O)NR 58 —, —SO 2 NR 59 —, —NR 60 SO 2 — or —NR 61 — (wherein R 57 , R 58 , R 59 , R 60  and R 61  each independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl), and R 56  is selected from one of the following twenty-two groups: 
 1) hydrogen, oxiranylC 1-4 alkyl or C 1-5 alkyl which may be unsubstituted or which may be substituted with one or more groups selected from hydroxy, fluoro, chloro, bromo and amino; 
 2) C 1-5 alkylX 11 C(O)R 62  (wherein X 11  represents —O— or —NR 63 — (in which R 63  represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) and R 62  represents C 1-3 alkyl, —NR 64 R 65  or —OR 66  (wherein R 64 , R 65  and R 66  which may be the same or different each represents hydrogen, C 1-5 alkyl or C 1-3 alkoxyC 2-3 alkyl)); 
 3) C 1-5 alkylX 12 R 67  (wherein X 12  represents —O—, —S—, —SO—, —SO 2 —, —OC(O)—, —NR 68 C(O)—, —C(O)NR 69 —, —SO 2 NR 70 —, —NR 71 SO 2 — or —NR 72 — (wherein R 68 , R 69 , R 70 , R 71  and R 72  each independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) and R 67  represents hydrogen, C 1-3 alkyl, cyclopentyl, cyclohexyl or a 5-6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which C 1-3 alkyl group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno and C 1-4 alkoxy and which cyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, cyano, C 1-4 cyanoalkyl, C 1-4 alkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 alkoxyC 1-4 alkyl, C 1-4 alkylsulphonylC 1-4 alkyl, C 1-4 alkoxycarbonyl, C 1-4 aminoalkyl, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 alkylaminoC 1-4 alkyl, di(C 1-4 alkyl)aminoC 1-4 alkyl, C 1-4 alkylaminoC 1-4 alkoxy, di(C 1-4 alkyl)aminoC 1-4 alkoxy and a group —(—O—) f (C 1-4 alkyl) g ringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 5-6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which cyclic group may bear one or more substituents selected from C 1-4 alkyl)); 
 4) C 1-5 alkylX 13 C 1-5 alkylX 14 R 73  (wherein X 13  and X 14  which may be the same or different are each —O—, —S—, —SO—, —SO 2 —, —NR 74 C(O)—, —C(O)NR 75 —, —SO 2 NR 76 —, —NR 77 SO 2 — or —NR 78 — (wherein R 74 , R 75 , R 76 , R 77  and R 78  each independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) and R 73  represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl); 
 5) R 79  (wherein R 79  is a 5-6-membered saturated heterocyclic group (linked via carbon or nitrogen) with 1-2 heteroatoms, selected independently from O, S and N, which heterocyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, cyano, C 1-4 cyanoalkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 alkoxyC 1-4 alkyl, C 1-4 alkylsulphonylC 1-4 alkyl, C 1-4 alkoxycarbonyl, C 1-4 aminoalkyl, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 alkylaminoC 1-4 alkyl, di(C 1-4 alkyl)aminoC 1-4 alkyl, C 1-4 alkylaminoC 1-4 alkoxy, di(C 1-4 alkyl)aminoC 1-4 alkoxy and a group —(—O—) f (C 1-4 alkyl) g ringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 5-6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which cyclic group may bear one or more substituents selected from C 1-4 alkyl)); 
 6) C 1-5 alkylR 79  (wherein R 79  is as defined herein); 
 7) C 2-5 alkenylR 79  (wherein R 79  is as defined herein); 
 8) C 2-5 alkynylR 79  (wherein R 79  is as defined herein); 
 9) R 80  (wherein R 80  represents a pyridone group, a phenyl group or a 5-6-membered aromatic heterocyclic group (linked via carbon or nitrogen) with 1-3 heteroatoms selected from O, N and S, which pyridone, phenyl or aromatic heterocyclic group may carry up to 5 substituents selected from oxo, hydroxy, halogeno, amino, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 hydroxyalkyl, C 1-4 aminoalkyl, C 1-4 alkylamino, C 1-4 hydroxyalkoxy, carboxy, trifluoromethyl, cyano, —C(O)NR 81 R 82 , —NR 83 C(O)R 84  (wherein R 81 , R 82 , R 83  and R 84 , which may be the same or different, each represents hydrogen, C 1-4 alkyl or C 1-3 alkoxyC 2-3 alkyl) and a group —(—O—) f (C 1-4 alkyl) g ringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 5-6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which cyclic group may bear one or more substituents selected from C 1-4 alkyl)); 
 10) C 1-5 alkylR 80  (wherein R 80  is as defined herein); 
 11) C 2-5 alkenylR 80  (wherein R 80  is as defined herein); 
 12) C 2-5 alkynylR 80  (wherein R 80  is as defined herein); 
 13) C 1-5 alkylX 15 R 80  (wherein X 15  represents —O—, —S—, —SO—, —SO 2 —, —NR 85 C(O)—, —C(O)NR 86 —, —SO 2 NR 87 —, —NR 88 SO 2 — or —NR 89 — (wherein R 85 , R 86 , R 87 , R 88  and R 89  each independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) and R 80  is as defined herein); 
 14) C 2-5 alkenylX 16 R 80  (wherein X 16  represents —O—, —S—, —SO—, —SO 2 —, —NR 90 C(O)—, —C(O)NR 91 —, —SO 2 NR 92 —, —NR 93 SO 2 — or —NR 94 — (wherein R 90 , R 91 , R 92 , R 93  and R 94  each independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) and R 80  is as defined herein); 
 15) C 2-5 alkynylX 17 R 80  (wherein X 17  represents —O—, —S—, —SO—, —SO 2 —, —NR 95 C(O)—, —C(O)NR 96 —, —SO 2 NR 97 —, —NR 98 SO 2 — or —NR 99 — (wherein R 95 , R 96 , R 97 , R 98  and R 99  each independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) and R 80  is as defined herein); 
 16) C 1-4 alkylX 18 C 1-4 alkylR 80  (wherein X 18  represents —O—, —S—, —SO—, —SO 2 —, —NR 100 C(O)—, —C(O)NR 101 —, —SO 2 NR 102 —, —NR 103 SO 2 — or —NR 104 — (wherein R 100 , R 101 , R 102 , R 103  and R 104  each independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) and R 80  is as defined herein); 
 17) C 1-4 alkylX 18 C 1-4 alkylR 79  (wherein X 18  and R 79  are as defined herein); 
 18) C 2-5 alkenyl which may be unsubstituted or which may be substituted with one or more groups selected from hydroxy, fluoro, amino, C 1-4 alkylamino,  N,N -di(C 1-4 alkyl)amino, aminosulphonyl,  N -C 1-4 alkylaminosulphonyl and  N,N -di(C 1-4 alkyl)aminosulphonyl; 
 19) C 2-5 alkynyl which may be unsubstituted or which may be substituted with one or more groups selected from hydroxy, fluoro, amino, C 1-4 alkylamino,  N,N -di(C 1-4 alkyl)amino, aminosulphonyl,  N -C 1-4 alkylaminosulphonyl and  N,N -di(C 1-4 alkyl)aminosulphonyl; 
 20) C 2-5 alkenylX 18 C 1-4 alkylR 79  (wherein X 18  and R 79  are as defined herein); 
 21) C 2-5 alkynylX 18 C 1-4 alkylR 79  (wherein X 18  and R 79  are as defined herein); and 
 22) C 1-4 alkylR 105 (C 1-4 alkyl) x (X 18 ) y R 106  (wherein X 18  is as defined herein, x is 0 or 1, y is 0 or 1, and R 105  and R 106  are each independently selected from hydrogen, C 1-3 alkyl, cyclopentyl, cyclohexyl and a 5-6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which C 1-3 alkyl group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno and C 1-4 alkoxy and which cyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, cyano, C 1-4 cyanoalkyl, C 1-4 alkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 alkoxyC 1-4 alkyl, C 1-4 alkylsulphonylC 1-4 alkyl, C 1-4 alkoxycarbonyl, C 1-4 aminoalkyl, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 alkylaminoC 1-4 alkyl, di(C 1-4 alkyl)aminoC 1-4 alkyl, C 1-4 alkylaminoC 1-4 alkoxy, di(C 1-4 alkyl)aminoC 1-4 alkoxy and a group —(—O—) f (C 1-4 alkyl) g ringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 5-6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which cyclic group may bear one or more substituents selected from C 1-4 alkyl) with the proviso that R 105  cannot be hydrogen); and additionally wherein any C 1-5 alkyl, C 2-5 alkenyl or C 2-5 alkynyl group in R 56 X 10 — which is linked to X 10  may bear one or more substituents selected from hydroxy, halogeno and amino); with the proviso that one or more R 1  and/or one or more R 2  are selected from Q 1 X 1 — wherein X 1  is as defined herein and Q 1  is selected from one of the following groups: 
 1) C 1-4 alkyl-Q 13 -C(O)—C 1-4 alkyl-Q 14  wherein Q 13  is C 1-3 alkyl, cyclopentyl, cyclohexyl and a 5-6-membered saturated or partially unsaturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which C 1-3 alkyl group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno and C 1-4 alkoxy and which cyclic group may bear either one substituent selected from methylenedioxy or ethylenedioxy to form a bicyclic ring, or may bear 1, 2 or 3 substituents selected from C 2-5 alkenyl, C 2-5 alkynyl, C 1-6 fluoroalkyl, C 1-6 alkanoyl, C 1-6 alkanoylC 1-6 alkyl, aminoC 1-6 alkanoyl, C 1-4 alkylaminoC 1-6 alkanoyl, di(C 1-4 alkyl)aminoC 1-6 alkanoyl, C 1-6 fluoroalkanoyl, carbamoyl, C 1-4 alkylcarbamoyl, di(C 1-4 alkyl)carbamoyl, carbamoylC 1-6 alkyl, C 1-4 alkylcarbamoylC 1-6 alkyl, di(C 1-4 alkyl)carbamoylC 1-6 alkyl, C 1-6 alkylsulphonyl, C 1-6 fluoroalkylsulphonyl, oxo, hydroxy, halogeno, cyano, C 1-4 cyanoalkyl, C 1-4 alkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 alkoxyC 1-4 alkyl, C 1-4 alkylsulphonylC 1-4 alkyl, C 1-4 alkoxycarbonyl, C 1-4 aminoalkyl, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 alkylaminoC 1-4 alkyl, di(C 1-4 alkyl)aminoC 1-4 alkyl, C 1-4 alkylaminoC 1-4 alkoxy, di(C 1-4 alkyl)aminoC 1-4 alkoxy and a group —(—O—) f (C 1-4 alkyl) g ringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 5-6-membered saturated or partially unsaturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which heterocyclic group may bear one or more substituents selected from C 1-4 alkyl), and Q 14  is a 5-6-membered saturated or partially unsaturated heterocyclic group containing at least one nitrogen atom and optionally containing a further nitrogen atom wherein Q 14  is linked to C 1-6 alkanoyl through a nitrogen atom and wherein Q 14  optionally bears either one substituent selected from methylenedioxy or ethylenedioxy to form a bicyclic ring, or bears 1, 2 or 3 substituents selected from C 2-5 alkenyl, C 2-5 alkynyl, C 1-6 fluoroalkyl, C 1-6 alkanoyl, C 1-6 alkanoylC 1-6 alkyl, aminoC 1-6 alkanoyl, C 1-4 alkylaminoC 1-6 alkanoyl, di(C 1-4 alkyl)aminoC 1-6 alkanoyl, C 1-6 fluoroalkanoyl, carbamoyl, C 1-4 alkylcarbamoyl, di(C 1-4 alkyl)carbamoyl, carbamoylC 1-6 alkyl, C 1-4 alkylcarbamoylC 1-6 alkyl, di(C 1-4 alkyl)carbamoylC 1-6 alkyl, C 1-6 alkylsulphonyl, C 1-6 fluoroalkylsulphonyl, oxo, hydroxy, halogeno, cyano, C 1-4 cyanoalkyl, C 1-4 alkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 alkylsulphonylC 1-4 alkyl, C 1-4 alkoxycarbonyl, C 1-4 aminoalkyl, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 alkylaminoC 1-4 alkyl, di(C 1-4 alkyl)aminoC 1-4 alkyl, C 1-4 alkylaminoC 1-4 alkoxy, di(C 1-4 alkyl)aminoC 1-4 alkoxy and a group —(—O—) f (C 1-4 alkyl) g ringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 5-6-membered saturated or partially unsaturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which heterocyclic group may bear one or more substituents selected from C 1-4 alkyl); 
 2) Q 2  (wherein Q 2  is a 5-6-membered saturated or partially unsaturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which heterocyclic group bears either one substituent selected from methylenedioxy or ethylenedioxy to form a bicyclic ring, or bears at least one substituent selected from C 1-6 alkanoylC 1-6 alkyl and optionally bears a further 1 or 2 substituents selected from C 2-5 alkenyl, C 2-5 alkynyl, C 1-6 fluoroalkyl, C 1-6 alkanoyl, C 1-6 alkanoylC 1-6 alkyl, aminoC 1-6 alkanoyl, C 1-4 alkylaminoC 1-6 alkanoyl, di(C 1-4 alkyl)aminoC 1-6 alkanoyl, C 1-6 fluoroalkanoyl, carbamoyl, C 1-4 alkylcarbamoyl, di(C 1-4 alkyl)carbamoyl, carbamoylC 1-6 alkyl, C 1-4 alkylcarbamoylC 1-6 alkyl, di(C 1-4 alkyl)carbamoylC 1-6 alkyl, C 1-6 alkylsulphonyl, C 1-6 fluoroalkylsulphonyl, oxo, hydroxy, halogeno, cyano, C 1-4 cyanoalkyl, C 1-4 alkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 alkoxyC 1-4 alkyl, C 1-4 alkylsulphonylC 1-4 alkyl, C 1-4 alkoxycarbonyl, C 1-4 aminoalkyl, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 alkylaminoC 1-4 alkyl, di(C 1-4 alkyl)aminoC 1-4 alkyl, C 1-4 alkylaminoC 1-4 alkoxy, di(C 1-4 alkyl)aminoC 1-4 alkoxy and a group —(—O—) f (C 1-4 alkyl) g ringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 5-6-membered saturated or partially unsaturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which cyclic group may bear one or more substituents selected from C 1-4 alkyl)); 
 3) C 1-5 alkylW 1 Q 2  (wherein W 1  represents —O—, —S—, —SO—, —SO 2 —, —OC(O)—, —NQ 3 C(O)—, —C(O)NQ 4 -, —SO 2 NQ 5 -, —NQ 6 SO 2 — or —NQ 7 - (wherein Q 3 , Q 4 , Q 5 , Q 6  and Q 7  each independently represents hydrogen, C 1-3 alkyl, C 1-3 alkoxyC 2-3 alkyl, C 2-5 alkenyl, C 2-5 alkynyl or C 1-4 haloalkyl) and Q 2  is as defined herein); 
 4) C 1-5 alkylQ 2  (wherein Q 2  is as defined herein); 
 5) C 2-5 alkenylQ 2  (wherein Q 2  is as defined herein); 
 6) C 2-5 alkynylQ 2  (wherein Q 2  is as defined herein); 
 7) C 1-4 alkylW 2 C 1-4 alkylQ 2  (wherein W 2  represents —O—, —S—, —SO—, —SO 2 —, —NQ 8 C(O)—, —C(O)NQ 9 -, —SO 2 NQ 10 -, —NQ 11 SO 2 — or —NQ 12 - (wherein Q 8 , Q 9 , Q 10 , Q 11  and Q 12  each independently represents hydrogen, C 1-3 alkyl, C 1-3 alkoxyC 2-3 alkyl, C 2-5 alkenyl, C 2-5 alkynyl or C 1-4 haloalkyl) and Q 2  is as defined herein); 
 8) C 2-5 alkenylW 2 C 1-4 alkylQ 2  (wherein W 2  and Q 2  are as defined herein); 
 9) C 2-5 alkynylW 2 C 1-4 alkylQ 2  (wherein W 2  and Q 2  are as defined herein); 
 10) C 1-4 alkylQ 15 (C 1-4 alkyl) j (W 2 ) k Q 16  (wherein W 2  is as defined herein, j is 0 or 1, k is 0 or 1, and Q 15  and Q 16  are each independently selected from hydrogen, C 1-3 alkyl, cyclopentyl, cyclohexyl and a 5-6-membered saturated or partially unsaturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which C 1-3 alkyl group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno and C 1-4 alkoxy and which cyclic group may bear either one substituent selected from methylenedioxy or ethylenedioxy to form a bicyclic ring, or may bear 1, 2 or 3 substituents selected from C 2-5 alkenyl, C 2-5 alkynyl, C 1-6 fluoroalkyl, C 1-6 alkanoyl, C 1-6 alkanoylC 1-6 alkyl, aminoC 1-6 alkanoyl, C 1-4 alkylaminoC 1-6 alkanoyl, di(C 1-4 alkyl)aminoC 1-6 alkanoyl, C 1-6 fluoroalkanoyl, carbamoyl, C 1-4 alkylcarbamoyl, di(C 1-4 alkyl)carbamoyl, carbamoylC 1-6 alkyl, C 1-4 alkylcarbamoylC 1-6 alkyl, di(C 1-4 alkyl)carbamoylC 1-6 alkyl, C 1-6 alkylsulphonyl, C 1-6 fluoroalkylsulphonyl, oxo, hydroxy, halogeno, cyano, C 1-4 cyanoalkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 alkoxyC 1-4 alkyl, C 1-4 alkylsulphonylC 1-4 alkyl, C 1-4 alkoxycarbonyl, C 1-4 aminoalkyl, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 alkylaminoC 1-4 alkyl, di(C 1-4 alkyl)aminoC 1-4 alkyl, C 1-4 alkylaminoC 1-4 alkoxy, di(C 1-4 alkyl)aminoC 1-4 alkoxy and a group —(—O—) f (C 1-4 alkyl) g ringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 5-6-membered saturated or partially unsaturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which heterocyclic group may bear one or more substituents selected from C 1-4 alkyl), with the provisos that Q 15  cannot be hydrogen and one or both of Q 15  and Q 16  must be a 5-6-membered saturated or partially unsaturated heterocyclic group as defined herein which heterocyclic group bears either one substituent selected from methylenedioxy or ethylenedioxy to form a bicyclic ring, or bears at least one substituent selected from C 1-6 alkanoylC 1-6 alkyl and optionally bears 1 or 2 further substituents selected from those defined herein); 
 11) C 1-4 alkylQ 15 C 1-4 alkanoylQ 16n  wherein Q 15  is as defined herein and is not hydrogen and Q 16n  is a 5-6-membered saturated or partially unsaturated heterocyclic group containing at least one nitrogen atom and optionally containing a further nitrogen atom wherein Q 16n  is linked to C 1-6 alkanoyl through a nitrogen atom and wherein Q 16n  bears either one substituent selected from methylenedioxy or ethylenedioxy to form a bicyclic ring, or bears 1, 2 or 3 substituents selected from C 2-5 alkenyl, C 2-5 alkynyl, C 1-6 fluoroalkyl, C 1-6 alkanoyl, C 1-6 alkanoylC 1-6 alkyl, aminoC 1-6 alkanoyl, C 1-4 alkylaminoC 1-6 alkanoyl, di(C 1-4 alkyl)aminoC 1-6 alkanoyl, C 1-6 fluoroalkanoyl, carbamoyl, C 1-4 alkylcarbamoyl, di(C 1-4 alkyl)carbamoyl, carbamoylC 1-6 alkyl, C 1-4 alkylcarbamoylC 1-6 alkyl, di(C 1-4 alkyl)carbamoylC 1-6 alkyl, C 1-6 alkylsulphonyl, C 1-6 fluoroalkylsulphonyl, oxo, hydroxy, halogeno, cyano, C 1-4 cyanoalkyl, C 1-4 alkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 alkoxyC 1-4 alkyl, C 1-4 alkylsulphonylC 1-4 alkyl, C 1-4 alkoxycarbonyl, C 1-4 aminoalkyl, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 alkylaminoC 1-4 alkyl, di(C 1-4 alkyl)aminoC 1-4 alkyl, C 1-4 alkylaminoC 1-4 alkoxy, di(C 1-4 alkyl)aminoC 1-4 alkoxy and a group —(—O—) f (C 1-4 alkyl) g ringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 5-6-membered saturated or partially unsaturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which heterocyclic group may bear one or more substituents selected from C 1-4 alkyl); with the proviso that one or both of Q 15  and Q 16n  must be a 5-6-membered saturated or partially unsaturated heterocyclic group as defined herein which heterocyclic group bears either one substituent selected from methylenedioxy or ethylenedioxy to form a bicyclic ring, or bears at least one substituent selected from C 1-6 alkanoylC 1-6 alkyl and optionally bears 1 or 2 further substituents selected from those defined herein; 
 and additionally wherein any C 1-5 alkyl, C 2-5 alkenyl or C 2-5 alkynyl group in Q 1 X 1 — which is linked to X 1  may bear one or more substituents selected from hydroxy, halogeno and amino); or a salt thereof. 
 
       
     
     
         2 . A compound according to  claim 1  wherein ring C is a 9-10-membered heteroaromatic bicyclic moiety which contains 1 or 2 nitrogen atoms. 
     
     
         3 . A compound according to  claim 1  wherein Z is —O— or —S—. 
     
     
         4 . A compound according to  claim 1  wherein R 1  represents methyl or fluoro. 
     
     
         5 . A compound according to  claim 1  of the formula IIb: 
       
         
           
           
               
               
           
         
         wherein: 
         M is —CH— or —N—; nc is 0, 1 or 2; R 2c  is linked to a carbon atom of the 5-membered ring and is selected from hydrogen and methyl; R 2d  is linked to a carbon atom of the 6-membered ring and is selected from hydrogen and fluoro; each independently selected from hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkylsulphanyl, —NR 3a R 4a  (wherein R 3a  and R 4a , which may be the same or different, each represents hydrogen or C 1-3 alkyl), and Q 1 X 1  wherein Q 1  and X 1  are as defined in  claim 1 ; Z a  is —O— or —S—; with the proviso that at least one of R 2a  and R 2b  is Q 1 X 1  wherein Q 1  and X 1  are as defined in  claim 1 ; 
         or a salt thereof. 
       
     
     
         6 . A compound according to  claim 5  wherein one of R 2a  and R 2b  is methoxy and the other is Q 1 X 1  wherein X 1  is —O— and Q 1  is selected from one of the following groups: 1) C 1-4 alkyl-Q 13 -C(O)—C 1-4 alkyl-Q 14  wherein Q 13  and Q 14  are each independently selected from pyrrolidinyl, piperidinyl, piperazinyl, 
       
         
           
           
               
               
           
         
         wherein Q 14  is linked to C 1-6 alkanoyl through a nitrogen atom; 
         2) Q 2  (wherein Q 2  is a 5-6-membered heterocyclic group selected from pyrrolidinyl, piperidinyl, piperazinyl, 
       
       
         
           
           
               
               
           
         
         which heterocyclic group bears either one substituent selected from methylenedioxy or ethylenedioxy to form a bicyclic ring, or bears at least one substituent selected from C 2-4 alkanoylC 1-3 alkyl and optionally bears a further 1 or 2 substituents selected from C 2-5 alkenyl, C 2-5 alkynyl, C 1-6 fluoroalkyl, C 1-6 alkanoyl, C 2-4 alkanoylC 1-3 alkyl, aminoC 1-6 alkanoyl, C 1-4 alkylaminoC 1-6 alkanoyl, di(C 1-4 alkyl)aminoC 1-6 alkanoyl, C 1-6 fluoroalkanoyl, carbamoyl, C 1-4 alkylcarbamoyl, di(C 1-4 alkyl)carbamoyl, carbamoylC 1-6 alkyl, C 1-4 alkylcarbamoylC 1-6 alkyl, di(C 1-4 alkyl)carbamoylC 1-6 alkyl, C 1-6 alkylsulphonyl, C 1-6 fluoroalkylsulphonyl, oxo, hydroxy, halogeno, cyano, C 1-4 cyanoalkyl, C 1-4 alkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 alkoxyC 1-4 alkyl, C 1-4 alkylsulphonylC 1-4 alkyl, C 1-4 alkoxycarbonyl, C 1-4 aminoalkyl, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 alkylaminoC 1-4 alkyl, di(C 1-4 alkyl)aminoC 1-4 alkyl, C 1-4 alkylaminoC 1-4 alkoxy, di(C 1-4 alkyl)aminoC 1-4 alkoxy and a group —(—O—) f (C 1-4 alkyl) g ringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 5-6-membered saturated or partially unsaturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which cyclic group may bear one or more substituents selected from C 1-4 alkyl)); 
         3) C 1-5 alkylQ 2  (wherein Q 2  is as defined herein); 
         4) C 1-4 alkylW 2 C 1-4 alkylQ 2  (wherein W 2  is as defined in  claim 1  and Q 2  is as defined herein); 
         5) C 1-4 alkylQ 15 (C 1-4 alkyl) j (W 2 ) k Q 16  (wherein W 2  is as defined in  claim 1 , j is 0 or 1, k is 0 or 1, and Q 15  and Q 16  are each independently selected from a 5-6-membered heterocyclic group selected from pyrrolidinyl, piperidinyl, piperazinyl, 
       
       
         
           
           
               
               
           
         
         which heterocyclic group may bear either one substituent selected from methylenedioxy or ethylenedioxy to form a bicyclic ring, or may bear 1, 2 or 3 substituents selected from C 2-5 alkenyl, C 2-5 alkynyl, C 1-6 fluoroalkyl, C 1-6 alkanoyl, C 2-4 alkanoylC 1-3 alkyl, aminoC 1-6 alkanoyl, C 1-4 alkylaminoC 1-6 alkanoyl, di(C 1-4 alkyl)aminoC 1-6 alkanoyl, C 1-6 fluoroalkanoyl, carbamoyl, C 1-4 alkylcarbamoyl, di(C 1-4 alkyl)carbamoyl, carbamoylC 1-6 alkyl, C 1-4 alkylcarbamoylC 1-6 alkyl, di(C 1-4 alkyl)carbamoylC 1-6 alkyl, C 1-6 alkylsulphonyl, C 1-6 fluoroalkylsulphonyl, oxo, hydroxy, halogeno, cyano, C 1-4 cyanoalkyl, C 1-4 alkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 alkoxyC 1-4 alkyl, C 1-4 alkylsulphonylC 1-4 alkyl, C 1-4 alkoxycarbonyl, C 1-4 aminoalkyl, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 alkylaminoC 1-4 alkyl, di(C 1-4 alkyl)aminoC 1-4 alkyl, C 1-4 alkylaminoC 1-4 alkoxy, di(C 1-4 alkyl)aminoC 1-4 alkoxy and a group —(—O—) f (C 1- 4alkyl) g ringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 5-6-membered saturated or partially unsaturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which heterocyclic group may bear one or more substituents selected from C 1-4 alkyl), with the proviso one or both of Q 15  and Q 16  must be a 5-6-membered heterocyclic group as defined herein which heterocyclic group bears either one substituent selected from methylenedioxy or ethylenedioxy to form a bicyclic ring, or bears at least one substituent selected from C 2-4 alkanoylC 1-3 alkyl and optionally bears 1 or 2 further substituents selected from those defined herein); 
         6) C 1-4 alkylQ 15 C 1-4 alkanoylQ 16n  wherein Q 15  is as defined herein and Q 16n  is a 5-6-membered heterocyclic group selected from pyrrolidinyl, piperidinyl, piperazinyl, 
       
       
         
           
           
               
               
           
         
         wherein Q 16n  is linked to C 1-6 alkanoyl through a nitrogen atom and wherein Q 16n  bears either one substituent selected from methylenedioxy or ethylenedioxy to form a bicyclic ring, or bears 1, 2 or 3 substituents selected from C 2-5 alkenyl, C 2-5 alkynyl, C 1-6 fluoroalkyl, C 1-6 alkanoyl, C 2-4 alkanoylC 1-3 alkyl, aminoC 1-6 alkanoyl, C 1-4 alkylaminoC 1-6 alkanoyl, di(C 1-4 alkyl)aminoC 1-6 alkanoyl, C 1-6 fluoroalkanoyl, carbamoyl, C 1-4 alkylcarbamoyl, di(C 1-4 alkyl)carbamoyl, carbamoylC 1-6 alkyl, C 1-4 alkylcarbamoylC 1-6 alkyl, di(C 1-4 alkyl)carbamoylC 1-6 alkyl, C 1-6 alkylsulphonyl, C 1-6 fluoroalkylsulphonyl, oxo, hydroxy, halogeno, cyano, C 1-4 cyanoalkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, C 1-4 alkoxyC 1-4 alkyl, C 1-4 alkylsulphonylC 1-4 alkyl, C 1-4 alkoxycarbonyl, C 1-4 aminoalkyl, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 alkylaminoC 1-4 alkyl, di(C 1-4 alkyl)aminoC 1-4 alkyl, C 1-4 alkylaminoC 1-4 alkoxy, di(C 1-4 alkyl)aminoC 1-4 alkoxy and a group —(—O—) f (C 1-4 alkyl) g ringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 5-6-membered saturated or partially unsaturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which heterocyclic group may bear one or more substituents selected from C 1-4 alkyl); with the proviso that one or both of Q 15  and Q 16n  must be a 5-6-membered heterocyclic group as defined herein which heterocyclic group bears either one substituent selected from methylenedioxy or ethylenedioxy to form a bicyclic ring, or bears at least one substituent selected from C 2-4 alkanoylC 1-3 alkyl and optionally bears 1 or 2 further substituents selected from those defined herein; and additionally wherein any C 1-5 alkyl, C 2-5 alkenyl or C 2-5 alkynyl group in  1 X 1 — which is linked to X 1  may bear one or more substituents selected from hydroxy, halogeno and amino). 
       
     
     
         7 . A compound according to  claim 5  wherein one of R 2a  and R 2b  is methoxy and the other is Q 1 X 1  wherein X 1  is —O— and Q 1  is C 1-4 alkyl-Q 13 -C(O)—C 1-4 alkyl-Q 14  wherein Q 13  and Q 14  are each independently selected from pyrrolidinyl, piperidinyl, piperazinyl, 
       
         
           
           
               
               
           
         
         wherein Q 14  is linked to C 1-6 alkanoyl through a nitrogen atom. 
       
     
     
         8 . A compound according to  claim 5  wherein one of R 2a  and R 2b  is methoxy and the other is Q 1 X 1  wherein X 1  is —O— and Q 1  is selected from one of the following groups:
 1) Q 2  (wherein Q 2  is a 5-6-membered heterocyclic group selected from pyrrolidinyl, piperidinyl, piperazinyl, 
 
       
         
           
           
               
               
           
         
         which heterocyclic group bears either one substituent selected from methylenedioxy or ethylenedioxy to form a bicyclic ring, or bears one substituent selected from C 2-4 alkanoylC 1-3 alkyl; and 
         2) C 1-5 alkylQ 2  (wherein Q 2  is as defined herein). 
       
     
     
         9 . A compound according to  claim 7  wherein R 2a  is methoxy. 
     
     
         10 . A compound according to  claim 1  selected from:
 7-{[1-(acetylmethyl)piperidin-4-yl]methoxy}-6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]quinazoline, 
 7-{([1-(acetylmethyl)piperidin-4-yl]methoxy}-6-methoxy-4-[(2-methyl-1H-indol-6-yl)oxy]quinazoline, 
 7-{[1-(acetylmethyl)piperidin-4-yl]methoxy}-6-methoxy-4-[(2-methyl-1H-indol-5-yl)oxy]quinazoline, 
 6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]-7-{[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]methoxy}quinazoline, 
 6-methoxy-4-[(2-methyl-1H-indol-6-yl)oxy]-7-{[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]methoxy}quinazoline, 
 6-methoxy-4-[(2-methyl-1H-indol-5-yl)oxy]-7-{[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]methoxy}quinazoline, 
 6-methoxy-4-[(2-methyl-1H-indol-5-yl)oxy]-7-[2-(tetrahydro-5H-[1,3]dioxolo[4,5-c]pyrrol-5-yl)ethoxy]quinazoline, 
 6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]-7-[2-(tetrahydro-5H-[1,3]dioxolo[4,5-c]pyrrol-5-yl)ethoxy]quinazoline, 
 4-[(2,3-dimethyl-1H-indol-5-yl)oxy]-6-methoxy-7-[2-(tetrahydro-5H-[1,3]dioxolo[4,5-c]pyrrol-5-yl)ethoxy]quinazoline, 
 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[2-(tetrahydro-5H-[1,3]dioxolo[4,5-c]pyrrol-5-yl)ethoxy]quinazoline, 
 7-{2-[4-(acetylmethyl)piperazin-1-yl]ethoxy}-4-[(2,3-dimethyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline, 
 7-{2-[4-(acetylmethyl)piperazin-1-yl]ethoxy}-6-methoxy-4-[(3-methyl-1H-indol-5yl)oxy]quinazoline, 
 7-{2-[4-(acetylmethyl)piperazin-1-yl]ethoxy}-6-methoxy-4-[(2-methyl-1H-indol-5-yl)oxy]quinazoline, 
 7-{2-[4-(acetylmethyl)piperazin-1-yl]ethoxy}-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline, 
 6-methoxy-4-[(2-methyl-1H-indol-5-yl)oxy]-7-{2-[4-(pyrrolidin-1-ylacetyl)piperazin-1-yl]ethoxy}quinazoline, 
 7-{[1-(acetylmethyl)piperidin-4-yl]oxy}-6-methoxy-4-[(2-methyl-1H-indol-6-yl)oxy]quinazoline, 
 7-{[1-(acetylmethyl)piperidin-4-yl]oxy}-6-methoxy-4-[(2-methyl-1H-indol-5-yl)oxy]quinazoline, 
 7-{[1-(acetylmethyl)piperidin-4-yl]oxy}-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline,
 or a salt thereof. 
 
 
     
     
         11 . A compound according to  claim 1  selected from:
 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[2-(tetrahydro-5H-[1,3]dioxolo[4,5-c]pyrrol-5-yl)ethoxy]quinazoline, 
 7-{2-[4-(acetylmethyl)piperazin-1-yl]ethoxy}-6-methoxy-4-[(2-methyl-1H-indol-5-yl)oxy]quinazoline, 
 7-{2-[4-(acetylmethyl)piperazin-1-yl]ethoxy}-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline, or a salt thereof. 
 
     
     
         12 . A compound according to  claim 1  in the form of a pharmaceutically acceptable salt. 
     
     
         13 . A process for the preparation of a compound according to  claim 1  of the formula I or salt thereof which comprises:
 (a) the reaction of a compound of the formula III: 
 
       
         
           
           
               
               
           
         
         (wherein R 2  and m are as defined in  claim 1  and L 1  is a displaceable moiety), with a compound of the formula IV: 
       
       
         
           
           
               
               
           
         
         (wherein ring C, R 1 , Z and n are as defined in  claim 1 ) optionally followed by the addition of a substituent on a heterocyclic ring of R 1  or R 2 ; 
         (b) for compounds of formula I and salts thereof wherein at least one R 2  is R 5 X 1  or Q 1 X 1  wherein R 5  and Q 1  are as defined in  claim 1 , and X 1  is —O—, —S—, —OC(O)— or —NR 10 — (wherein R 10  independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) the reaction of a compound of the formula V: 
       
       
         
           
           
               
               
           
         
         (wherein ring C, Z, R 2  and n are as defined in  claim 1  and X 1  is as defined in this section and s is an integer from 0 to 2) with one of the compounds of the formulae VIa-b:
   R 5 -L 1   (VIa)
 
   Q 1 -L 1   (VIb)
 
 
         (wherein R 5  and Q 1  are as defined in  claim 1  and L 1  is as defined herein); 
         (c) for compounds of the formula I and salts thereof wherein at least one R 2  is R 5 X 1  or Q 1 X 1  wherein R 5  and Q 1  are as defined in  claim 1 , and X 1  is —O—, —S—, —OC(O)— or —NR 10 — (wherein R 10  represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) the reaction of a compound of the formula VII: 
       
       
         
           
           
               
               
           
         
         with one of the compounds of the formulae VIIIa-b:
   R 5 —X 1 —H  (VIIIa)
 
   Q 1 -X 1 —H  (VIIIb)
 
 
         (wherein R 1 , R 2 , R 5 , Q 1 , ring C, Z and n are as defined in  claim 1 , L 1  and s are as defined herein and X 1  is as defined in this section; 
         (d) for compounds of the formula I and salts thereof wherein at least one R 2  is R 5 X 1  or Q 1 X 1  wherein X 1  is as defined in  claim 1 , R 5  is C 1-5 alkylR 113 , wherein R 113  is selected from one of the following nine groups: 
         1) X 19 C 1-3 alkyl (wherein X 19  represents —O—, —S—, —SO 2 —, —NR 114 C(O)— or —NR 115 SO 2 — (wherein R 114  and R 115  which may be the same or different are each hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl); 
         2)NR 116 R 117  (wherein R 116  and R 117  which may be the same or different are each hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl); 
         3) X 20 C 1-5 alkylX 5 R 22  (wherein X 20  represents —O—, —S—, —SO 2 —, —NR 118 C(O)—, —NR 119 SO 2 — or —NR 120 — (wherein R 118 , R 119 , and R 120  which may be the same or different are each hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) and X 5  and R 22  are as defined in  claim 1 ); 
         4) R 28  (wherein R 28  is as defined in  claim 1 ); 
         5) X 21 R 29  (wherein X 21  represents —O—, —S—, —SO 2 —, —NR 121 C(O)—, —NR 122 — su or —NR 123 — (wherein R 121 , R 122 , and R 123  which may be the same or different are each hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) and R 29  is as defined in  claim 1 ); 
         6) X 22 C 1-3 alkylR 29  (wherein X 22  represents —O—, —S—, —SO 2 —, —NR 124 C(O)—, —NR 125 SO 2 — or —NR 126 — (wherein R 124 , R 125  and R 126  each independently represents hydrogen, C 1-3 alkyl or C 1-3 alkoxyC 2-3 alkyl) and R 29  is as defined in  claim 1 ); 
         7) R 29  (wherein R 29  is as defined in  claim 1 ); 
         8) X 22 C 1-4 alkylR 28  (wherein X 22  and R 28  are as defined in  claim 1 ); and 
         9) R 54 (C 1-4 alkyl) q (X 9 ) r R 55  (wherein q, r, X 9 , R 54  and R 55  are as defined in  claim 1 ); 
         Q 1  is C 1-5 alkylQ 27  wherein Q 27  is selected from one of the following six groups: 
         1) Q 13 -C(O)—C 1-4 alkylQ 14  (wherein Q 13  and Q 14  are as defined in  claim 1 ); 
         2) W 1 Q 2 (wherein W 1  and Q 2  are as defined in  claim 1 ); 
         3) Q 2  (wherein Q 2  is as defined in  claim 1 ); 
         4) W 2 C 1-4 alkylQ 2  (wherein W 2  and Q 2  are as defined in  claim 1 ); 
         5) Q 15 (C 1-4 alkyl) j (W 2 ) k Q 16  (wherein W 2 , j, k, Q 15  and Q 16  are as defined in  claim 1 ); 
         6) Q 15 C 1-4 alkanoylQ 16n  (wherein Q 15  and Q 16n  are as defined in  claim 1 ); 
         the reaction of a compound of the formula IX: 
       
       
         
           
           
               
               
           
         
       
       (wherein X 1 , R 1 , R 2 , ring C, Z and n are as defined in  claim 1  and L 1  and s are as defined herein) with one of the compounds of the formulae Xa-b:
   R 113 —H  (Xa)
 
   Q 27 -H  (Xb)
 
 
       (wherein R 113  and Q 27  are as defined herein) optionally followed by the addition of a substituent on a heterocyclic ring of R 1  or R 2 ;
 and when a salt of a compound of formula I is required, reaction of the compound obtained with an acid or base whereby to obtain the desired salt. 
 
     
     
         14 . A pharmaceutical composition which comprises a compound of the formula I as defined in  claim 1  or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable excipient or carrier. 
     
     
         15 . Use of a compound of the formula I as defined in  claim 1  or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in a warm-blooded animal. 
     
     
         16 . A method for producing an antiangiogenic and/or vascular permeability reducing effect in a warm-blooded animal, such as a human being, in need of such treatment which comprises administering to said animal an effective amount of a compound of formula I as defined in  claim 1  or a pharmaceutically acceptable salt thereof.