HRP20191460T1

HRP20191460T1 - Compounds useful for treating cancer

Info

Publication number: HRP20191460T1
Authority: HR
Inventors: Pierre Roux; Florence Mahuteau; Romain Najman; Jamal Tazi; Gilles Gadea; Didier Scherrer; Carsten Brock; Nathalie Cahuzac
Original assignee: Abivax; Centre Nat Rech Scient; Inst Curie; Univ Montpellier
Priority date: 2009-06-12
Filing date: 2019-08-12
Publication date: 2019-11-15
Also published as: JP2018162290A; JP2016128463A; JP6149127B2; JP6378802B2; JP2016135776A; JP2018162292A; JP6606577B2; JP2016128462A; JP6149128B2; JP2018162291A; MX2019008390A; JP6149129B2; JP6419243B2; JP6336650B2; JP6694476B2; JP2017137341A; JP2016147850A; JP2017137342A; JP6154922B2; JP6150445B2

Claims

1. Spoj s formulom (I): naznačen time što: predstavlja aromatski prsten pri čemu V je C, R neovisno predstavlja vodikov atom, halogeni atom ili skupinu koja se bira između skupine -CN, hidroksilne skupine, skupine -COOR1, skupine (C1-C3)fluoroalkil, skupine (C1-C3)fluoroalkoksi, skupine -NO2, skupine -NR1R2, skupine (C1-C4)alkoksi, fenoksi skupine i skupine (C1-C3)alkil, navedeni alkil je po izboru mono-supstituiran s hidroksilnom skupinom, R1 i R2 su neovisno vodikov atom ili skupina (C1-C3)alkil, n je 1, 2 ili 3, n' je 1 ili 2, R' je vodikov atom, halogeni atom ili skupinu koja se bira između skupine (C1-C3)alkil, skupine -COOR1, skupine -NO2, skupine -NR1R2, morfolinil skupine ili morfolino skupine, skupine N-metilpiperazinil, skupine (C1-C3)fluoroalkil, skupine (C1-C4)alkoksi i skupine -CN, R" je vodikov atom ili skupina (C1-C4)alkil, Z je N, V je C, Y je N, X je C, T je C, U je C i W je C, ili bilo koja od njegovih farmaceutski prihvatljivih soli, za upotrebu kao sredstvo za prevenciju, inhibiranje ili liječenje raka.1. Compound with formula (I): characterized by: represents an aromatic ring where V is C, R independently represents a hydrogen atom, a halogen atom or a group selected from the group -CN, hydroxyl group, group -COOR1, group (C1-C3)fluoroalkyl, group (C1-C3)fluoroalkoxy, group -NO2, group -NR1R2, group (C1-C4)Alkoxy, phenoxy groups and (C1-C3)alkyl groups, said alkyl is optionally mono-substituted with a hydroxyl group, R1 and R2 are independently a hydrogen atom or a (C1-C3)alkyl group, n is 1, 2 or 3, n' is 1 or 2, R' is a hydrogen atom, a halogen atom or a group selected from the (C1-C3)alkyl group, the -COOR1 group, the -NO2 group, the -NR1R2 group, the morpholinyl group or the morpholino group, the N-methylpiperazinyl group, the (C1-C3 )fluoroalkyl, (C1-C4) alkoxy groups and -CN groups, R" is a hydrogen atom or a (C1-C4)alkyl group, Z is N, V is C, Y is N, X is C, T is C, U is C and W is C, or any of its pharmaceutically acceptable salts, for use as an agent for the prevention, inhibition or treatment of cancer.

2. Spoj s formulom (I) prema patentnom zahtjevu 1, za upotrebu kao sredstvo za prevenciju, inhibiranje ili liječenje raka, koji je s formulom (Ia) naznačen time što: R neovisno predstavlja vodikov atom, halogeni atom ili skupinu koja se bira između skupine (C1-C3)alkil, skupine -CN, hidroksilne skupine, skupine -COOR1, skupine (C1-C3)fluoroalkil, skupine -NO2, skupine -NR1R2 i skupine (C1-C3)alkoksi, R" je kako je definirano u zahtjevu 1 i povoljno je vodikov atom, n je kako je definirano u zahtjevu 1 i povoljno je 1, n' je kako je definirano u zahtjevu 1 i povoljno je 1, R' je vodikov atom, halogeni atom ili skupinu koja se bira između skupine (C1-C3)alkil, skupine -NO2, skupine (C1-C3)alkoksi i skupine -NR1R2, R1 i R2 su vodikov atom ili skupina (C1-C3)alkil, ili jedna od njegovih farmaceutski prihvatljivih soli.2. A compound of formula (I) according to claim 1, for use as an agent for preventing, inhibiting or treating cancer, which is of formula (Ia) characterized by: R independently represents a hydrogen atom, a halogen atom or a group selected from the group (C1-C3)alkyl, the group -CN, the hydroxyl group, the group -COOR1, the group (C1-C3)fluoroalkyl, the group -NO2, the group -NR1R2 and the group (C1-C3)Alkoxy, R" is as defined in claim 1 and is preferably a hydrogen atom, n is as defined in claim 1 and is preferably 1, n' is as defined in claim 1 and is preferably 1, R' is a hydrogen atom, a halogen atom or a group selected from the group (C1-C3)alkyl, the group -NO2, the group (C1-C3)alkoxy and the group -NR1R2, R1 and R2 are a hydrogen atom or a (C1-C3)alkyl group, or one of its pharmaceutically acceptable salts.

3. Spoj s formulom (I) prema bilo kojem od prethodnih patentnih zahtjeva, za upotrebu kao sredstvo za prevenciju, inhibiranje ili liječenje raka, koji je s formulom (Ia) naznačen time što: R neovisno predstavlja vodikov atom, halogeni atom ili skupinu koja se bira između skupine (C1-C3)alkil, skupine -CN, skupine -COOR1 i skupine (C1-C3)fluoroalkil, R1 je vodikov atom ili skupina (C1-C3)alkil, R" je kako je definirano u zahtjevu 1 i poželjnije je vodikov atom, n je kako je definirano u zahtjevu 1 i poželjnije je 1, n' je kako je definirano u zahtjevu 1, R' je vodikov atom, halogeni atom ili skupina (C1-C3)alkil, ili jedna od njegovih farmaceutski prihvatljivih soli.3. A compound of formula (I) according to any of the preceding claims, for use as an agent for preventing, inhibiting or treating cancer, which is of formula (Ia) characterized by: R independently represents a hydrogen atom, a halogen atom or a group selected from the group (C1-C3)alkyl, the group -CN, the group -COOR1 and the group (C1-C3)fluoroalkyl, R1 is a hydrogen atom or a (C1-C3)alkyl group, R" is as defined in claim 1 and is more preferably a hydrogen atom, n is as defined in claim 1 and is preferably 1, n' is as defined in claim 1, R' is a hydrogen atom, a halogen atom or a (C1-C3)alkyl group, or one of its pharmaceutically acceptable salts.

4. Spoj naznačen time što je odabran iz niza koji čine: - (1) (8-Kloro-kinolin-2-il)-piridin-2-il-amin - (2) 2-(Kinolin-2-ilamino)-izonikotinska kiselina - (3) (4-Metil-piridin-2-il)-kinolin-2-il-amin - (4) Piridin-2-il-kinolin-2-il-amin - (5) 2-(8-Kloro-kinolin-2-ilamino)-izonikotinska kiselina - (6) (8-Kloro-kinolin-2-il)-(4-metil-piridin-2-il)-amin - (7) 6-(Kinolin-2-ilamino)-nikotinonitril - (17) N-(6-metilpiridin-2-il)kinolin-2-amin - (18) 8-kloro-N-(6-metilpiridin-2-il)kinolin-2-amin - (19) 4-metil-N-(piridin-2-il)kinolin-2-amin - (20) 4-metil-N-(4-metilpiridin-2-il)kinolin-2-amin - (21) 3-metil-N-(4-metilpiridin-2-il)kinolin-2-amin - (22) 3-metil-N-(piridin-2-il)kinolin-2-amin - (23) 6-((4-metilkinolin-2-il)amino)nikotinonitril - (24) 6-((3-metilkinolin-2-il)amino)nikotinonitril - (25) 6-kloro-N-(4-metilpiridin-2-il)kinolin-2-amin - (26) 6-kloro-N-(6-metilpiridin-2-il)kinolin-2-amin - (27) 4-metil-N-(5-nitropiridin-2-il)kinolin-2-amin - (28) N-(3-nitropiridin-2-il)kinolin-2-amin - (29) 8-kloro-N-(3-nitropiridin-2-il)kinolin-2-amin - (30) 2-((4-metilkinolin-2-il)amino)nikotinonitril - (31) N-(3-metilpiridin-2-il)kinolin-2-amin - (32) N-(5-metilpiridin-2-il)kinolin-2-amin - (33) 2-(kinolin-2-ilamino)izonikotinonitril - (34) N-(5-(trifluorometil)piridin-2-il)kinolin-2-amin - (35) 8-kloro-N-(3-metilpiridin-2-il)kinolin-2-amin - (36) 8-kloro-N-(5-metilpiridin-2-il)kinolin-2-amin - (37) 8-kloro-N-(5-(trifluorometil)piridin-2-il)kinolin-2-amin - (38) N-(3-methoksipiridin-2-il)kinolin-2-amin - (39) N-(5-nitropiridin-2-il)kinolin-2-amin - (40) 6-((8-klorokinolin-2-il)amino)nikotinonitril - (41) N-(5-fluoropiridin-2-il)kinolin-2-amin - (42) N-(6-(trifluorometil)piridin-2-il)kinolin-2-amin - (43) 8-kloro-N-(5-fluoropiridin-2-il)kinolin-2-amin - (44) 2-((8-klorokinolin-2-il)amino)nikotinska kiselina - (45) 4-metil-N-(6-metilpiridin-2-il)kinolin-2-amin - (46) 3-metil-N-(6-metilpiridin-2-il)kinolin-2-amin - (47) 5-cijano-2-(kinolin-2-ilamino)piridin-1-ium klorid - (48) 2-((8-klorokinolin-2-il)amino)-4-metilpiridin-1-ium klorid - (49) 8-kloro-N-(4-etilpiridin-2-il)kinolin-2-amin - (50) 8-kloro-N-(6-etilpiridin-2-il)kinolin-2-amin - (51) 8-kloro-N-(4,6-dimetilpiridin-2-il)kinolin-2-amin - (52) 6-((8-klorokinolin-2-il)amino)-2-metilnikotinonitril - (53) 8-kloro-N-(4-kloropiridin-2-il)kinolin-2-amin - (54) 8-metil-N-(4-metilpiridin-2-il)kinolin-2-amin - (55) N-(5-bromo-4-metilpiridin-2-il)-8-klorokinolin-2-amin - (56) 8-kloro-N-(3-etil-6-metilpiridin-2-il)kinolin-2-amin - (57) 8-fluoro-N-(4-metilpiridin-2-il)kinolin-2-amin - (58) 8-bromo-N-(4-metilpiridin-2-il)kinolin-2-amin - (59) metil 6-(kinolin-2-ilamino)nikotinat - (60) metil 6-[(8-klorokinolin-2-il)amino]piridin-3-karboksilat - (61) metil 6-[(3-metilkinolin-2-il)amino]piridin-3-karboksilat - (62) metil 2-[(8-klorokinolin-2-il)amino]piridin-3-karboksilat - (63) 8-methoksi-N-(4-metilpiridin-2-il)kinolin-2-amin - (64) N-(4-metilpiridin-2-il)-5-nitrokinolin-2-amin - (65) 2-N-(4-metilpiridin-2-il)kinolin-2,8-diamin - (66) N-(4-metilpiridin-2-il)-5-aminokinolin-2-amin - (67) metil 6-[(4-metilkinolin-2-il)amino]piridin-3-karboksilat - (68) 8-kloro-N-[4-(trifluorometil)piridin-2-il]kinolin-2-amin - (69) 2-[(8-klorokinolin-2-il)amino]piridin-3-ol - (70) 8-kloro-N-[6-(trifluorometil)piridin-2-il]kinolin-2-amin - (71) 6-kloro-N-(5-fluoropiridin-2-il)kinolin-2-amin - (72) N-(6-etilpiridin-2-il)-3-metilkinolin-2-amin - (73) N-(5-fluoropiridin-2-il)-3-metilkinolin-2-amin - (74) 3-metil-N-[5-(trifluorometil)piridin-2-il]kinolin-2-amin - (150) N-(4-metilpiridin-2-il)-8-nitrokinolin-2-amin - (151) 6-kloro-N-(6-etilpiridin-2-il)kinolin-2-amin - (152) 6-kloro-N-(5-metilpiridin-2-il)kinolin-2-amin - (153) 6-kloro-N-[5-(trifluorometil)piridin-2-il]kinolin-2-amin - (154) N2-(8-klorokinolin-2-il)-4-metilpiridin-2,3-diamin - i njihove farmaceutski prihvatljive soli, za upotrebu kao sredstvo za prevenciju, inhibiranje ili liječenje raka.4. A compound characterized by the fact that it is selected from the series consisting of: - (1) (8-Chloro-quinolin-2-yl)-pyridin-2-yl-amine - (2) 2-(Quinolin-2-ylamino)-isonicotinic acid - (3) (4-Methyl-pyridin-2-yl)-quinolin-2-yl-amine - (4) Pyridin-2-yl-quinolin-2-yl-amine - (5) 2-(8-Chloro-quinolin-2-ylamino)-isonicotinic acid - (6) (8-Chloro-quinolin-2-yl)-(4-methyl-pyridin-2-yl)-amine - (7) 6-(Quinolin-2-ylamino)-nicotinonitrile - (17) N-(6-methylpyridin-2-yl)quinolin-2-amine - (18) 8-chloro-N-(6-methylpyridin-2-yl)quinolin-2-amine - (19) 4-methyl-N-(pyridin-2-yl)quinolin-2-amine - (20) 4-methyl-N-(4-methylpyridin-2-yl)quinolin-2-amine - (21) 3-methyl-N-(4-methylpyridin-2-yl)quinolin-2-amine - (22) 3-methyl-N-(pyridin-2-yl)quinolin-2-amine - (23) 6-((4-methylquinolin-2-yl)amino)nicotinonitrile - (24) 6-((3-methylquinolin-2-yl)amino)nicotinonitrile - (25) 6-chloro-N-(4-methylpyridin-2-yl)quinolin-2-amine - (26) 6-chloro-N-(6-methylpyridin-2-yl)quinolin-2-amine - (27) 4-methyl-N-(5-nitropyridin-2-yl)quinolin-2-amine - (28) N-(3-nitropyridin-2-yl)quinolin-2-amine - (29) 8-chloro-N-(3-nitropyridin-2-yl)quinolin-2-amine - (30) 2-((4-methylquinolin-2-yl)amino)nicotinonitrile - (31) N-(3-methylpyridin-2-yl)quinolin-2-amine - (32) N-(5-methylpyridin-2-yl)quinolin-2-amine - (33) 2-(quinolin-2-ylamino)isonicotinonitrile - (34) N-(5-(trifluoromethyl)pyridin-2-yl)quinolin-2-amine - (35) 8-chloro-N-(3-methylpyridin-2-yl)quinolin-2-amine - (36) 8-chloro-N-(5-methylpyridin-2-yl)quinolin-2-amine - (37) 8-chloro-N-(5-(trifluoromethyl)pyridin-2-yl)quinolin-2-amine - (38) N-(3-methoxypyridin-2-yl)quinolin-2-amine - (39) N-(5-nitropyridin-2-yl)quinolin-2-amine - (40) 6-((8-chloroquinolin-2-yl)amino)nicotinonitrile - (41) N-(5-fluoropyridin-2-yl)quinolin-2-amine - (42) N-(6-(trifluoromethyl)pyridin-2-yl)quinolin-2-amine - (43) 8-chloro-N-(5-fluoropyridin-2-yl)quinolin-2-amine - (44) 2-((8-chloroquinolin-2-yl)amino)nicotinic acid - (45) 4-methyl-N-(6-methylpyridin-2-yl)quinolin-2-amine - (46) 3-methyl-N-(6-methylpyridin-2-yl)quinolin-2-amine - (47) 5-cyano-2-(quinolin-2-ylamino)pyridin-1-ium chloride - (48) 2-((8-chloroquinolin-2-yl)amino)-4-methylpyridin-1-ium chloride - (49) 8-chloro-N-(4-ethylpyridin-2-yl)quinolin-2-amine - (50) 8-chloro-N-(6-ethylpyridin-2-yl)quinolin-2-amine - (51) 8-chloro-N-(4,6-dimethylpyridin-2-yl)quinolin-2-amine - (52) 6-((8-chloroquinolin-2-yl)amino)-2-methylnicotinonitrile - (53) 8-chloro-N-(4-chloropyridin-2-yl)quinolin-2-amine - (54) 8-methyl-N-(4-methylpyridin-2-yl)quinolin-2-amine - (55) N-(5-bromo-4-methylpyridin-2-yl)-8-chloroquinolin-2-amine - (56) 8-chloro-N-(3-ethyl-6-methylpyridin-2-yl)quinolin-2-amine - (57) 8-fluoro-N-(4-methylpyridin-2-yl)quinolin-2-amine - (58) 8-bromo-N-(4-methylpyridin-2-yl)quinolin-2-amine - (59) methyl 6-(quinolin-2-ylamino)nicotinate - (60) methyl 6-[(8-chloroquinolin-2-yl)amino]pyridine-3-carboxylate - (61) methyl 6-[(3-methylquinolin-2-yl)amino]pyridine-3-carboxylate - (62) methyl 2-[(8-chloroquinolin-2-yl)amino]pyridine-3-carboxylate - (63) 8-methoxy-N-(4-methylpyridin-2-yl)quinolin-2-amine - (64) N-(4-methylpyridin-2-yl)-5-nitroquinolin-2-amine - (65) 2-N-(4-methylpyridin-2-yl)quinolin-2,8-diamine - (66) N-(4-methylpyridin-2-yl)-5-aminoquinolin-2-amine - (67) methyl 6-[(4-methylquinolin-2-yl)amino]pyridine-3-carboxylate - (68) 8-chloro-N-[4-(trifluoromethyl)pyridin-2-yl]quinolin-2-amine - (69) 2-[(8-chloroquinolin-2-yl)amino]pyridin-3-ol - (70) 8-chloro-N-[6-(trifluoromethyl)pyridin-2-yl]quinolin-2-amine - (71) 6-chloro-N-(5-fluoropyridin-2-yl)quinolin-2-amine - (72) N-(6-ethylpyridin-2-yl)-3-methylquinolin-2-amine - (73) N-(5-fluoropyridin-2-yl)-3-methylquinolin-2-amine - (74) 3-methyl-N-[5-(trifluoromethyl)pyridin-2-yl]quinolin-2-amine - (150) N-(4-methylpyridin-2-yl)-8-nitroquinolin-2-amine - (151) 6-chloro-N-(6-ethylpyridin-2-yl)quinolin-2-amine - (152) 6-chloro-N-(5-methylpyridin-2-yl)quinolin-2-amine - (153) 6-chloro-N-[5-(trifluoromethyl)pyridin-2-yl]quinolin-2-amine - (154) N2-(8-chloroquinolin-2-yl)-4-methylpyridin-2,3-diamine - and their pharmaceutically acceptable salts, for use as an agent for the prevention, inhibition or treatment of cancer.