Patent ID: 6414148
Filing Date: 2002-07-02
Classification: A61F,A61K,A61P,C07D

Abstract:
A quinazoline derivative of the formula I: wherein:m is an integer from 1 to 2; R1 represents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, C1-3alkyl, C1-3alkoxy, C1-3alkylthio, or â€”NR5R6 (wherein R5 and R6, which may be the same or different, each represents hydrogen or C1-3alkyl); R2 represents hydrogen, hydroxy, halogeno, methoxy, amino or nitro; R3 represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; X1 represents â€”Oâ€”, R4 is selected from one of the following eleven groups: 1) C1-5alkylR12 (wherein R12 is a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which heterocyclic group is linked to C1-5alkyl through a carbon atom and which heterocyclic group may bear one or two substituent selected from oxo, hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl, C1-4alkoxy, carbamoyl, C1-4alkylcarbamoyl, N,N-di(C1-4alkyl)carbamoyl, C1-4alkanoyl and C1-4alkoxycarbonyl) or C1-5alkylR13 (wherein R13 is a group selected from pyrrolidin-1-yl, imidazolidin-1-yl and thiomorpholino, which group may bear one or two substituent selected from oxo, hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl, C1-4alkoxy, carbamoyl, C1-4alkylcarbamoyl, N,N-di(C1-4alkyl)carbamoyl, C1-4alkanoyl and C1-4alkoxycarbonyl); 2) C2-5alkenylR14 (wherein R14 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 substituent selected from oxo, hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl, C1-4alkoxy, carbamoyl, C1-4alkylcarbamoyl, N,N-di(C1-4alkyl)carbamoyl, C1-4alkanoyl and C1-4alkoxycarbonyl); 3) C3-5alkynylR15 (wherein R15 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 substituent selected from oxo, hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl, C1-4alkoxy, carbamoyl, C1-4alkylcarbamoyl, N,N-di(C1-4alkyl)carbamoyl, C1-4alkanoyl and C1-4alkoxycarbonyl); 4) C1-5alkylX2C1-5alkylX3R16 (wherein X2 and X3 which may be the same or different are each â€”Oâ€”, â€”Sâ€”, â€”SOâ€”, â€”SO2â€”, â€”NR17COâ€”, â€”CONR18â€”, â€”SO2NR19â€”, â€”NR20SO2â€” or â€”NR21â€” (wherein R17, R18, R19, R20 and R21 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R16 represents hydrogen or C1-3alkyl); 5) C1-5alkylX4COR22 (wherein X4 represents â€”Oâ€” or â€”NR23â€” (wherein R23 represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R22 represents â€”NR24R25 or â€”OR26 (wherein R24, R25 and R26 which may be the same or different each represents hydrogen, C1-4alkyl or C1-3alkoxyC2-3alkyl)); 6) C1-5alkylX5R27 (wherein X5 represents â€”Oâ€”, â€”Sâ€”, â€”SOâ€”, â€”SO2â€”, â€”OCOâ€”, â€”NR28COâ€”, â€”CONR29â€”, â€”SO2NR30â€”, â€”NR31SO2â€” or â€”NR32â€” (wherein R28, R29, R30, R31 and R32 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) or X5 is carbonyl, and R27 represents cyclopentyl, cyclohexyl or a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which cyclopentyl, cyclohexyl or heterocyclic group may bear one or two substituent selected from oxo, hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl, C1-4alkoxy, carbamoyl, C1-4alkylcarbamoyl, N,N-di(C1-4alkyl)carbamoyl, C1-4alkanoyl and C1-4alkoxycarbonyl or R27 is C1-3allyl with the proviso that when R27 is C1-3alkyl, X5 is â€”Sâ€”, â€”SOâ€”, â€”SO2â€”, â€”SO2NR30â€” or â€”NR31SO2â€”; 7) C1-3alkoxyC2-4alkyl or C1-4alkyl; 8) C1-5alkylX6C1-5alkylR33 (wherein X6 represents â€”Oâ€”, â€”Sâ€”, â€”SOâ€”, â€”SO2â€”, â€”NR34COâ€”, â€”CONR35â€”, â€”SO2NR36â€”, â€”NR37SO2â€” or â€”NR38â€” (wherein R34, R35, R36, R37 and R38 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl) and R33 represents cyclopentyl, cyclohexyl or a 5 or 6 membered saturated heterocyclic group with one or two heteroatoms, selected independently from O, S and N, which cyclopentyl, cyclohexyl or heterocyclic group may bear one or two substitutes selected from oxo, hydroxy, halogeno, C1-4alkyl), C1-4hydroxyalkyl, C1-4alkoxy, carbamoyl, C1-4alkylcarbamoyl, N,N-di(C1-4alkyl)carbamoyl, C1-4alkanoyl and C1-4alkoxycarbonyl); 9) R39 (wherein R39 is a group selected from pyrrolidin-3-yl, piperidine-3-yl and piperidine-4-yl which group may bear one or two substituent selected from oxo, hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl, C1-4alkoxy, carbamoyl, C1-4alkylcarbamoyl, N,N-di(C1-4alkyl)carbamoyl, C1-4alkanoyl and C1-4alkoxycarbonyl); 10) C1-5alkylR40 (wherein R40 is piperazin-1-yl which bears at least one substituent selected from C1-4alkanoyl, C1-4alkoxycarbonyl, C1-4hydroxyalkyl and â€”CONR41R42 (wherein R41 and R42 each independently represents hydrogen or C1-4alkyl); and 11) C1-5alkylR44 (wherein R44 is morpholino which bears at least one and optionally two substituent selected from oxo, C1-4alkyl, C1-4hydroxyalkyl, carbamoyl, C1-4alkylcarbamoyl, N,N-di(C1-4alkyl)carbamoyl, C1-4alkanoyl and C1-4alkoxycarbonyl); with the further proviso that when R4 is selected from group 7) R1 and/or R2 is/are nitro or at least one R3 is C1-3alkanoyloxy; or a salt thereof.