Cinnoline derivatives and use as medicine

The use of a compound of the formula I:

• 30
• wherein:
• Z represents —O—, —NH—, —S— or —CH2—;
• m is an integer from 1 to 5;
• R1 represents hydrogen, hydroxy, halogeno, nitro, cyano, trifluoromethyl, C1-3alkyl, C1-3alkoxy, C1-3alkylthio or NR6R7 (wherein R6 and R7, which may be the same or different, each represents hydrogen or C1-3alkyl);
• R2 represents hydrogen, hydroxy, fluoro, chloro, methoxy, amino or nitro;
• R3 represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro;
• R4 represents hydrogen, hydroxy, halogeno, cyano, nitro, amino, trifluoromethyl, C1-3alkyl or a group R5—X1 (wherein X1 represents —O—, —CH2—, —S—, —SO—, —SO2—, —NR8CO—, —CONR9—, —SO2NR10—, —NR11SO2— or —NR12— (wherein R8, R9, R10, R11 and R12 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R5 is selected from one of the following fourteen groups:
• 1) C1-5alkyl, C1-5hydroxyalkyl, C1-5fluoroalkyl, C1-5aminoalkyl;
• 2) C1-5alkylX2COR13 (wherein X2 represents —O— or NR14 (in which R14 represents hydrogen, C1-3 alkyl or C1-3alkoxyC2-3alkyl) and R13 represents C1-3alkyl, NR15R16 or OR17 (wherein R15, R16 and R17 which may be the same or different are each hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl), with the proviso that when X2 is —O—, R13 is not OR17);
• 3) C1-5alkylX3R18 (wherein X3 represents —O—, —S—, —SO—, —SO2—, —OCO—, —NR19CO—, —CONR20—, —SO2NR21—, —NR22SO2— or —NR23— (wherein R19, R20, R21, R22 and R23 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R18 represents hydrogen, C1-3alkyl, cyclopentyl, cyclohexyl or a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which C1-3alkyl group may bear one or two substituents selected from oxo, hydroxy, halogeno and C1-4alkoxy and which cyclic group may bear one or two substituents selected from oxo, hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl and C1-4alkoxy);
• 4) C1-5alkylX4C1-5alkylX5R24 (wherein X4 and X5 which may be the same or different are each —O—, —S—, —SO—, —SO2—, —NR25CO—, —CONR26—, —SO2NR27—, —NR28SO2— or —NR29— (wherein R25, R26, R27, R28 and R29 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R24 represents hydrogen or C1-3alkyl);
• 5) C1-5alkylR30 (wherein R30 is a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which heterocyclic group may bear one or two substituents selected from oxo, hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl and C1-4alkoxy);
• 6) C2-5alkenylR30 (wherein R30 is as defined herein);
• 7) C2-5alkynylR30 (wherein R30 is as defined herein);
• 8) (CH2)nR31 (wherein n is an integer from 0 to 5 and R31 is a phenyl group, a pyridone group or a 5 or 6 membered aromatic heterocyclic group with 1 to 3 heteroatoms selected from O, N and S, which phenyl, pyridone or aromatic heterocyclic group may carry up to 5 substituents selected from hydroxy, halogeno, C1-4alkyl, C1-4alkoxy, C1-4hydroxyalkyl, C1-4hydroxyalkoxy, carboxy, cyano, CONR32R33 and NR34COR35 (wherein R32, R33, R34 and R35, which may be the same or different, each represents hydrogen, C1-4alkyl or C1-3alkoxyC2-3alkyl);
• 9) C2-5alkenylR31 (wherein R31 is as defined herein);
• 10) C2-5alkynylR31 (wherein R31 is as defined herein);
• 11) C1-5alkylX6R31 (wherein X6 represents —O—, —S—, —SO—, —SO2—, —NR36CO—, —CONR37—, —SO2NR38—, —NR39SO2— or —NR40— (wherein R36, R37, R38, R39 and R40 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R31 is as defined herein);
• 12) C2-5alkenylX7R31 (wherein X7 represents —O—, —S—, —SO—, —SO2—, —NR41CO—, —CONR42—, —SO2NR43—, —NR44SO2— or —NR45— (wherein R41, R42, R43, R44 and R45 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R31 is as defined herein);
• 13) C2-5alkynylX8R31 (wherein X8 represents —O—, —S—, —SO—, —SO2—, —NR46CO—, —CONR47—, —SO2NR48—, —NR49SO2— or —NR50— (wherein R46, R47, R48, R49 and R50 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R31 is as defined herein);
• 14) C1-3alkylX9C1-3alkylR31 (wherein X9 represents —O—, —S—, —SO—, —SO2—, —NR51CO—, —CONR52—, —SO2NR53—, —NR54SO2— or —NR55— (wherein R51, R52, R53, R54 and R55 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R31 is as defined herein))];
• and salts 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 such as a human being.