Patent NZ-334125-A (NZ)
Title: Quinoline derivatives inhibiting the effect of growth factors such as VEGF
Inventor: THOMAS ANDREW PETER
IPC: C07D521/00
Filed: 1997-09-23
Abstract: The use of a compound of the formula above wherein:  R represents hydroxy, halogeno, alkyl, alkoxy, alkanoyloxy, trifluoromethyl, cyano, amino or nitro;  n is an integer from 0 to 5;  Z represents -O-, -NH-, -S- or -CH2-;  G represents phenyl or a heteroaromatic cyclic or bicyclic group;  Y1, Y2, Y3 and Y4 each independently represents carbon or nitrogen with the proviso that they are not all nitrogen;  R' represents fluoro or hydrogen;  m is an integer from 1 to 3;  R3 represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, alkyl, -NR4R5 (wherein R4 and R5, which may be the same or different, each represents hydrogen or C, 3alkyl), or a group R6-X'- wherein X' represents -O-, -CH2-, -OCO-, carbonyl, -S-, -SO-, SO2-, -NR7CO-, -CONR8-, -SO2NR9-, -NR10SO2- or -NR"- (wherein R7, R8, R9, R10 and R" each independently represents hydrogen, alkyl or alkoxyC2-3alkyl) and R6 is selected from one of the following sixteen groups;  1) optionally substituted alkyl;  2) alkylXCOR12 (wherein X represents -0- or -NR13- (wherein R13 represents hydrogen, alkyl or alkoxyalkyl) and R'2 represents -NR'4R'5- or -OR16- (wherein R'4, R'5 and R'6 which may be the same or different each represents hydrogen, alkyl or alkoxyalkyl));  3) alkylX3 R17 (wherein X3 represents -O-, -S-, -SO-, -SO2-, -OCO-, -NR18CO-. CONR19-, -SO2NR20-, -NR21SO2- or -NR22- (wherein R18, R19, R20, R21 and R22 each independently represents hydrogen, alkyl or alkoxyalkyl) and R17 represents hydrogen, alkyl, cyclopentyl, cyclohexyl or a saturated heterocyclic group;  4) alkylX4alkylX5R23 (wherein X4 and X5 which may be the same or different are each -O-, -S-, -SO-, -SO2-, -NR24CO-, -CONR25-, -SO2NR26-, -NR27SO2- or -NR28- (wherein R24, R25, R26, R27 and R28 each independently represents hydrogen alkyl or alkoxyalkyl) and R23 represents hydrogen or alkyl);  5) alkylR29 (wherein R29 is an optionally substituted saturated heterocyclic group;  6) (CH2)qX6R30 (wherein q is an integer from 0 to 5, X6 represents a direct bond, -0--S-, SO-, -SO2-, -NR31CO-, -CONR32-, -SO2NR33-, -NR34SO2- or -NR35- (wherein R31, R32, R33,, R34 and R35 each independently represents hydrogen, alkyl or alkoxyalkyl) and R30 is an optionally substituted phenyl group, a pyridone group or a 5 or 6 membered aromatic heterocyclic group;  7) alkenylR29;  8) alkynylR29;  9) X7R40 (wherein X7 is -SO2-, -O-, or -CONR41R42- (wherein R4l and R42, which may be the same or different, each represents hydrogen, alkyl or alkoxyalkyl) and R40 represents optionally substituted alkyl) with the provisos that when X7 is SO2-, X'is -O-, when X7 is -O-, X' is carbonyl, when X7 is -CONR41R42-, X' is -O- or NR11;  10) alkenylR30;  11) alkynylR30;  12) alkenylX8R30 (wherein X8 represents -O-, -S-, -SO-, -SO2-, -NR43CO-, -CONR44-, SO2NR45-, -NR46So,- or -NR4'- (wherein R43, R44, R45 R46 and R47 each independently represents hydrogen alkyl or alkoxyalkyl);  13) alkynylX9R30 (wherein X9 represents -O-, -S-, -SO2-, -NR48CO-, -CONR49-, SO2NR50-, -NR51SO2- or -NR52- (wherein R48, R49, R50, R51 and R52 each independently represents hydrogen, alkyl or alkoxyalkyl);  14) C1-3alkylX10C1-3alkylR30 (wherein X10 represents -O-, -S-, -SO2-, -NR53CO-, CONR54-. -SO2NR5 -, -NR56SO2- or -NR57- (wherein R53, R54 R55, R56 and R57 each independently represents hydrogen, alkyl or alkoxyalkyl);  15) R29  and 16) C1-3alkylX10C1-3alkylR29; and salts 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.