Chemical compounds

The use of a compound of the formula I:

• wherein:
• ring C is a 9 or 10-membered bicyclic heteroaromatic group containing at least one nitrogen atom in the ring attached to Z and optionally containing a further 1-3 heteroatoms, selected independently from O, S and N, with the proviso that ring C is not a quinazoline, quinoline or cinnoline group;
• either any one of G1, G2, G3, G4 and G5 is nitrogen and the other four are —CH—, or G1, G2, G3, G4 and G5 are all —CH—;
• Z is —O—, —NH— or —S—;
• Z is linked to any one of G1, G2, G3 and G4 which is a free carbon atom;
• n is an integer from 0 to 5;
• any of the substituents R1 may be attached at any free carbon atom of the indole, azaindole or indazole group, such free carbon atoms may be G1, G2, G3, G4 or G5 or may be at the 3-position of the indole, azaindole or indazole group;
• m is an integer from 0 to 2;
• Rb represents hydrogen, C1-4alkyl, C1-4alkoxyC1-4alkyl, aminoC1-4alkyl, C1-3alkylaminoC1-4alkyl, di(C1-3alkyl)aminoC1-4alkyl, C2-5alkenylaminoC1-4alkyl, C2-5alkynylaminoC1-4alkyl, —C1-5alkyl(ring A) wherein ring A is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholino and thiomorpholino and wherein ring A may bear one or more substituents selected from C1-4alkyl, C2-5alkenyl, C2-5alkyl, hydroxy, oxo, halogeno, cyano, cyanoC1-4alkyl, C1-4alkylsulphonyl and C1-4alkanoyl;
• R1 represents hydrogen, oxo, hydroxy, halogeno, C1-4alkyl, C1-4alkoxy, C1-4alkoxyC1-4alkyl, aminoC1-4alkyl, C1-3alkylaminoC1-4alkyl, di(C1-3alkyl)aminoC1-4alkyl, —C1-5alkyl(ring B) wherein ring B is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, N-methylpiperazinyl, N-ethylpiperazinyl, morpholino and thiomorpholino;
• R2 represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C1-3alkyl, C1-3alkoxy, C1-3alkylsulphanyl, —NR3R4 (wherein R3 and R4, which may be the same or different, each represents hydrogen or C1-3alkyl), or R5X— (wherein X1 represents a direct bond, —O—, —CH2—, —OC(O)—, —C(O)—, —S—, —SO—, —SO2—, —NR6C(O)—, —C(O)NR7—, —SO2NR8—, —NR9SO2— or —NR10—(wherein R6, R7, R8, R9 and R10 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl), and R5 is selected from one of the following twenty-two groups:
• 1) hydrogen, oxiranylC1-4alkyl or C1-5alkyl which may be unsubstituted or which may be substituted with one or more groups selected from hydroxy, fluoro, chloro, bromo and amino;
• 2) C1-5alkylX2C(O)R11 (wherein X2 represents —O— or —NR12— (in which R12 represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R11 represents C1-3alkyl, —NR13R14 or —OR15 (wherein R13, R14 and R15 which may be the same or different each represents hydrogen, C1-5alkyl or C1-3alkoxyC2-3alkyl));
• 3) C1-5alkylX3R16 (wherein X3 represents —O—, —S—, —SO—, —SO2—, —OC(O)—, —NR17C(O)—, —C(O)NR15—, —SO2NR19—, —NR20SO2— or —NR21— (wherein R7, R5, R19, R20 and R21 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R16 represents hydrogen, C1-3alkyl, cyclopentyl, cyclohexyl or a 4-, 5- or 6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which C1-3alkyl group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno and C1-4alkoxy and which cyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, cyano, C1-4cyanoalkyl, C1-4alkyl, C1-4hydroxyalkyl, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4alkylsulphonylC1-4alkyl, C1-4alkoxycarbonyl, C1-4aminoalkyl, C1-4alkylamino, di(C1-4alkyl)amino, C1-4alkylaminoC1-4alkoxy, di(C1-4alkyl)aminoC1-4alkyl, C1-4alkylaminoC1-4alkoxy, di(C1-4alkyl)aminoC1-4alkoxy and a group —(—O—)f(C1-4alkyl)gringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 4-, 5- or 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 C1-4alkyl));
• 4) C1-5alkylX4C1-5alkylX5R22 (wherein X4 and X5 which may be the same or different are each —O—, —SO—, —SO2—, —NR23C(O)—C(O)NR24—, —SO2NR25—, —NR26SO2— or NR27 (wherein R23, R24, R25, R26 and R27 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R22 represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl);
• 5) R28 (wherein R28 is a 4-, 5- or 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, C1-4cyanoalkyl, C1-4alkyl, C1-4hydroxyalkyl, C1-4alkoxy, C1-4alkanoyl, C1-4alkoxyC1-4alkyl, C1-4alkylsulphonyl, C1-4alkylsulphonylC1-4alkyl, C1-4alkoxycarbonyl, C1-4aminoalkyl, C1-4alkylamino, di(C1-4alkyl)amino, C1-4alkylaminoC1-4alkyl, di(C1-4alkyl)aminoC1-4alkyl, C1-4alkylaminoC1-4alkoxy, di(C1-4alkyl)aminoC1-4alkoxy and a group —(—O—)f(C1-4alkyl)gringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 4-, 5- or 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 C1-4alkyl));
• 6) C1-5alkylR28 (wherein R28 is as defined herein);
• 7) C2-5alkenylR28 (wherein R28 is as defined herein);
• 8) C2-5alkynylR28 (wherein R28 is as defined herein);
• 9) R29 (wherein R29 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 hydroxy, halogeno, amino, C1-4alkyl, C1-4alkoxy, C1-4hydroxyalkyl, C1-4aminoalkyl, C1-4alkylamino, C1-4hydroxyalkoxy, carboxy, trifluoromethyl, cyano, —C(O)NR30R31, —NR32C(O)R33 (wherein R30, R31, R32 and R33, which may be the same or different, each represents hydrogen, C1-4alkyl or C1-3alkoxyC2-3alkyl) and a group —(—O—)f(C1-4alkyl)gringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 4-, 5- or 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 C1-4alkyl));
• 10) C1-5alkylR29 (wherein R29 is as defined herein);
• 11) C2-5alkenylR29 (wherein R29 is as defined herein);
• 12) C2-5alkynylR29 (wherein R29 is as defined herein);
• 13) C1-5alkylX6R29 (wherein X6 represents —O—, —S—, —SO—, —SO2—, —NR34C(O)—, —C(O)NR35—, —SO2NR36—, —NR37SO2— or —NR38— (wherein R34, R35, R36, R37 and R38 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R29 is as defined herein);
• 14) C2-5alkenylX7R29 (wherein X7 represents —O—, —S—, —SO—, —SO2—, —NR39C(O)—, —C(O)NR40—, —SO2NR41—, —NR42SO2— or —NR43 — (wherein R39, R40, R41, R42 and R43 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R29 is as defined herein);
• 15) C2-5alkynylX8R29 (wherein X8 represents —O—, —S—, —SO—, —SO2—, —NR44C(O)—, —C(O)NR45—, —SO2NR46—, —NR47SO2— or —NR38— (wherein R44, R45, R46, R47 and R41 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R29 is as defined herein);
• 16) C1-4alkylX9C1-4alkylR29 (wherein X9 represents —O—, —S—, —SO—, —SO2—, —NR49C(O)—, —C(O)NR50—, —SO2NR51—, NR52SO2— or —NR53— (wherein R49, R50, R51, R52 and R53 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R29 is as defined herein);
• 17) C1-4alkylX9C1-4alkylR28 (wherein X9 and R21 are as defined herein);
• 18) C2-5alkenyl which may be unsubstituted or which may be substituted with one or more groups selected from hydroxy, fluoro, amino, C1-4alkylamino, N,N-di(C1-4alkyl)amino, aminosulphonyl, N—C1-4alkylaminosulphonyl and N,N-di(C1-4alkyl)aminosulphonyl;
• 19) C2-5alkynyl which may be unsubstituted or which may be substituted with one or more groups selected from hydroxy, fluoro, amino, C4alkylamino, N,N-di(C1-4alkyl)amino, aminosulphonyl, N—C1-4alkylaminosulphonyl and N,N-di(C1-4alkyl)aminosulphonyl;
• 20) C2-5alkenylX9C1-4alkylR28 (wherein X9 and R28 are as defined herein);
• 21) C2-5alkynylX9C1-4alkylR28 (wherein X9 and R28 are as defined herein);
• and
• 22) C1-4alkylR54(C1-4alkyl)q(X9)rR55 (wherein X9 is as defined herein, q is 0 or 1, r is 0 or 1, and R54 and R55 are each independently selected from hydrogen, C1-3alkyl, cyclopentyl, cyclohexyl and a 4-, 5- or 6-membered saturated heterocyclic group with 1-2 heteroatoms, selected independently from O, S and N, which C1-3alkyl group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno and C1-4alkoxy and which cyclic group may bear 1 or 2 substituents selected from oxo, hydroxy, halogeno, cyano, C1-4cyanoalkyl, C1-4alkyl, C1-4hydroxyalkyl, C1-4alkoxy, C1-4alkoxyC1-4alkyl, C1-4alkylsulphonylC1-4alkyl, C1-4alkoxycarbonyl, C1-4aminoalkyl, C1-4alkylamino, di(C1-4alkyl)amino, C1-4alkylaminoC1-4alkyl, di(C1-4alkyl)aminoC1-4alkyl, C1-4alkylaminoC1-4alkoxy, di(C1-4alkyl)aminoC1-4alkoxy and a group —(—O—)f(C1-4alkyl)gringD (wherein f is 0 or 1, g is 0 or 1 and ring D is a 4-, 5- or 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 C1-4alkyl), with the proviso that R54 cannot be hydrogen);
• and additionally wherein any C1-5-alkyl, C2-5alkenyl or C2-5alkynyl group in R5X1— may bear one or more substituents selected from hydroxy, halogeno and amino);
• with the proviso that when ring C is
• wherein Z is as defined herein, (but Z is not a part of ring C, it is shown for the purposes of clarity), at least one R2 does not have a value selected from hydrogen, halogeno, C1-4alkyl, C1-4alkoxy and NRcRd (wherein each of Rc and Rd independently represents hydrogen, C1-4alkyl or phenyl which phenyl may bear 1-3 substituents selected from halogeno, trifluoromethyl, C1-4alkyl and C1-4alkoxy);
• or a salt thereof in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals such as humans.