NOVEL POLYQUINOLINE DERIVATIVES AND THERAPEUTIC USE THEREOF
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Abstract
The invention relates to compounds of general formula (I), to the process for the preparation thereof and to the use thereof as a therapeutic agent.
25 Citations
44 Claims
-
1-22. -22. (canceled)
-
23. A method for chelating metal ion and/or dissolving amyloid aggregates, comprising chelating metal ions and/or dissolving amyloid aggregates with a compound of formula (I)
wherein in formula (I) either X represents an — - OR, —
NRR′
, —
S(O)pR, —
OCOR or —
OCOOR group, andY represents a group of formula; in which X′
represents an —
OR, —
NRR′
, —
S(O)pR, —
OCOR or —
OCOOR group and Z represents a group of formula -(A)m-(Alk)n-(A′
)m′
-(Alk′
)n′
-(A″
)m″
-(Alk″
)n″
, where m, n, m′
, n′
, m″ and
n″
are the same or different and independently represent 0 or 1, it being understood that at least one of m, n, m′
, n′
m″ and
n″
is equal to 1,A, A′ and
A″
are the same or different and independently represent a group selected from —
NR—
, —
S(O)p-, —
O— and
—
C(═
O)—
, or a 4-11 membered ring selected from cycloalkyls, heterocycles, aryls and heteroaryls, said ring being optionally substituted by one or more substituents selected from alkyl, OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
;Alk, Alk′ and
Alk″
are the same or different and independently represent an -alkyl- group optionally substituted by one or more substituents selected from OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
;
orX represents a group of formula; in which Z represents a group of formula -(A)m-(Alk)n-(A′
)m′
-(Alk′
)n′
-(A″
)m″
-(Alk″
)n″
, where m, n, m′
, n′
, m″ and
n″
are the same or different and independently represent 0 or 1, it being understood that at least one of m, n, m′
, n′
m″ and
n″
is equal to 1,A, A′ and
A″
are the same or different and independently represent a group selected from —
NR—
, —
S(O)p-, —
O— and
—
C(═
O)—
, or a 4-11 membered ring selected from cycloalkyls, heterocycles, aryls and heteroaryls, said ring being optionally substituted by one or more substituents selected from alkyl, OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
;Alk, Alk′ and
Alk″
are the same or different and independently represent an -alkyl- group, optionally substituted by one or more substituents selected from OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
;Y represents a group selected from H, OR, NRR′
, Hal, —
CN, —
CF3 and alkyl optionally substituted by one or more substituents selected from OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
; andR and R′
are the same or different and independently represent a hydrogen atom or a cycloalkyl or alkyl group optionally substituted by one or more groups selected from OR, NRR′
, Hal, —
CN, —
CF3, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
;
heteroaryl;
R1, R2, R3, R4, R5, R11, R2′
, R3, R4′
, R5′ and
R6′
are the same or different and independently represent a group or atom selected from H, OR, NRR′
, Hal, —
CN, —
CF3, S(O)pR, COOR, OCOOR, CONRR′
, NRCOOR′ and
alkyl optionally substituted by one or more groups selected from OR, NRR′
, Hal, —
CN, —
CF3, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
;k represents 1 or 2; p represents 0, 1 or 2; as well as the pharmaceutically acceptable stereoisomers or mixtures, tautomeric forms, hydrates, solvates, salts, free forms and esters thereof, with the exception of compounds for which; X represents an —
OH group, andY represents a group of formula; in which X′
represents an —
OH group, andZ represents a group selected from —
NH—
, —
NBu-, —
NMe-, andR1, R2, R3, R4, R5, R1′
, R2′
, R3′
, R4′
, R5′ and
R6′
are equal to H.- View Dependent Claims (24, 25, 42, 44)
2,2′ - -methanediyl-bis(8-hydroxyquinoline,
2,2′
-methanediyl-bis(5-chloro-8-hydroxyquinoline),2,2′
-(2,2-propanediyl)-bis(8-hydroxyquinoline),2,2′
-(2,2-propanediyl)-bis(5-chloro-8-hydroxyquinoline),2,2′
-(difluoromethanediyl)-bis(8-hydroxyquinoline),bis(8-hydroxy-2-quinolinyl)methanone, 2,2′
-(1,2-ethanediyl)-bis[8-(methyloxy)quinoline],2,2′
-(1,2-ethanediyl)-bis(8-hydroxyquinoline),2,2′
-(1,2-ethanediyl)-bis(5-chloro-8-hydroxyquinoline),2,2′
-(1,2-ethanediyl)-bis(5-chloro-7-iodo-8-hydroxyquinoline),2,2′
-(1,4-butanediyl)-bis[8-(methyloxy)quinoline],2,2′
-(1,4-butanediyl)-bis(8-hydroxyquinoline),2,2′
,2″
-(1,2,3-propanetriol)-tris[8-(methyloxy)quinoline],2,2′
,2″
-(1,2,3-propanetriol)-tris(8-hydroxyquinoline),bis(8-quinolinyl)amine, N,N′
-di-8-quinolinyl-1,3-propanediamine,8,8′
-oxydiquinoline,N,N′
-bis(2-methyl-8-quinolinyl)-1,2-ethanediamine,dimethyl bis{7-(methyloxy)-8-[phenylmethyl)oxy]-2quinolinyl}propanedioate, 2,2′
-(methanediyl)-bis(7-methyloxy-8-hydroxy-2-quinolinium) dichloride,2,2′
-(1,2-ethanediyl)-bis[7-(methyloxy)-8-quinolinol],8-hydroxy-N-(8-hydroxy-2-quinolinyl)-2-quinoline carboxamide, 2-{[8-hydroxy-2-quinolinyl)amino]methyl}-8-quinolinol, 2,2′
-(iminodimethanediyl)di(N-boc-8-quinoline amine),2,2′
-(Iminodimethanediyl)di(8-quinoline amine),2,2′
,2″
-(nitrilotrimethanediyl)tri(N-boc-8-quinoline amine),2,2′
,2″
-(nitrilotrimethanediyl)tri(8-quinoline amine),2,2′
-[(butylimino)dimethanediyl]di(N-boc-8-quinoline amine),2,2′
-[(butylimino)dimethanediyl]di(8-quinoline amine),N-butyl-2,2′
-imino-bis(8-quinoline amine),N-8-quinolinyl-8-quinoline carboxamide, and N-8-quinolinyl-8-quinoline sulfonamide, as well as the pharmaceutically acceptable stereoisomers or mixtures, tautomeric forms, hydrates, solvates, salts, free forms and esters thereof.
- OR, —
-
25. The method according to claim 23, wherein said metals are selected from zinc, copper and/or iron.
-
42. The method according to claim 25, wherein X represents OR and Y represents a group of formula (IY), in which X′
- represents OR and Z represents A, where A represents —
C(O)—
or Z represents Alk, where Alk represents a linear or branched alkyl group optionally substituted by one or more halogen atoms;
orX represents OR and Y represents a group of formula (IY), in which X′
represents OR and Z represents A-A′
, where A represents —
C(O)— and
A′
represents NR′
;
orX represents OR and Y represents a group of formula (IY), in which X′
represents OR and Z represents A-Alk, where A represents NR′ and
Alk represents a linear or branched alkyl group optionally substituted by one or more halogen atoms;
orX represents NRR′ and
Y represents a group of formula (IY) in which X′
represents NRR′ and
Z represents Alk-NR″
-Alk, where Alk represents a linear or branched alkyl group optionally substituted by one or more halogen atoms;
orX represents NRR′ and
Y represents a group of formula (IY), in which X′
represents NRR′ and
Z represents NR″
;
orX represents a group of formula (IX), in which Z represents —
NR—
, —
NR-Alk-NR—
, —
O—
, —
NR—
C(O)—
ou —
NR—
S(O)2— and
Y represents H;k=1 or 2 R═
H or COOR′
or alkyl, optionally substituted, R′
═
H or alkyl, optionally substituted, R″
═
H, alkyl or heteroaryl optionally substituted, andR1, R2, R3, R4, R5, R1, R2′
, R3, R4′
, R5′ and
R6′
are the same or different and independently represent a group or atom selected from H, OR, NRR′
, Hal, —
CN, —
CF3 and alkyl optionally substituted by one or more substituents selected from OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
.
- represents OR and Z represents A, where A represents —
-
44. The method according to claim 25, wherein the compound is selected from bis(8-quinolinyl)amine and 2,2′
- -(2,2-propanediyl)-bis-(hydroxyquinoline), said compounds having no mutagenic or bactericidal effect.
-
26. A method for treating and/or preventing diseases that affect the central nervous system, comprising administering to a patient in need thereof an effective amount of a compounds of formula (I)
wherein in formula (I): -
either X represents an —
OR, —
NRR′
, —
S(O)pR, —
OCOR or —
OCOOR group andY represents a group of formula; in which X′
represents an —
OR, —
NRR′
, —
S(O)pR, —
OCOR or —
OCOOR group andZ represents a group of formula -(A)m-(Alk)n-(A′
)m′
-(Alk′
)n′
-(A″
)m″
-(Alk″
)n″
, wherem, n, m′
, n′
, m″ and
n″
are the same or different and independently represent 0 or 1, it being understood that at least one of m, n, m′
, n′
m″ and
n″
is equal to 1, A, A′ and
A″
are the same or different and independently represent a group selected from —
NR—
, —
S(O)p—
, —
O— and
—
C(═
O)—
, or a 4-11 membered ring selected from cycloalkyls, heterocycles, aryls and heteroaryls, said ring being optionally substituted by one or more substituents selected from alkyl, OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
;Alk, Alk′ and
Alk″
are the same or different and independently represent an -alkyl- group, optionally substituted by one or more substituents selected from OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
;
orX represents a group of formula; in which Z represents a group of formula -(A)n-(Alk)n-(A′
)m′
-(Alk′
)n′
-(A″
)m″
-(Alk″
)n″
where m, n, m′
, n′
, m″ and
n″
are the same or different and independently represent 0 or 1, it being understood that at least one of m, n, m′
, n′
m″ and
n″
is equal to 1,A, A′ and
A″
are the same or different and independently represent a group selected from —
NR—
, —
S(O)p—
, —
O— and
—
C(═
O)—
, or a 4-11 membered ring selected from cycloalkyls, heterocycles, aryls and heteroaryls, said ring being optionally substituted by one or more substituents selected from alkyl, OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
;Alk, Alk′ and
Alk″
are the same or different and independently represent an -alkyl- group, optionally substituted by one or more substituents selected from OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
;Y represents a group selected from H, OR, NRR′
, Hal, —
CN, —
CF3 and alkyl optionally substituted by one or more substituents selected from OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
; andR and R′
are the same or different and independently represent a hydrogen atom or a cycloalkyl or alkyl group, optionally substituted by one or more groups selected from OR, NRR′
, Hal, —
CN, —
CF3, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
;
heteroaryl;R1, R2, R3, R4, R5, R11, R2′
, R3, R4′
, R5′ and
R6′
are the same or different and independently represent a group or atom selected from H, OR, NRR′
, Hal, —
CN, —
CF3, S(O)pR, COOR, OCOOR, CONRR′
, NRCOOR″
, and alkyl optionally substituted by one or more substituents selected from OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
;k represents 1 or 2; p represents 0, 1 or 2; as well as the pharmaceutically acceptable stereoisomers or mixtures, tautomeric forms, hydrates, solvates, salts, free forms and esters thereof, with the exception of compounds for which; X represents an —
OH group, andY represents a group of formula; in which X′
represents an —
OH group,Z represents a group selected from —
NBu-, —
NMe-, andR1, R2, R3, R4, R5, R1′
, R2′
, R3′
, R4′
, R5′ and
R6′
are equal to Hand compounds for which X represents a group of formula; in which Z represents a group of formula —
(NH)—
(CH2)2—
(NH)—
(CH2)2—
(NH)—
,Y represents H R1, R2, R3, R4, R5, R1′
, R2′
, R3′
, R4′
, R5′ and
R6′
represent H.- View Dependent Claims (27, 28)
2,2′ - -methanediyl-bis(8-hydroxyquinoline),
2,2′
-methanediyl-bis(5-chloro-8-hydroxyquinoline),2,2′
-(2,2-propanediyl)-bis(8-hydroxyquinoline),2,2′
-(2,2-propanediyl)-bis(5-chloro-8-hydroxyquinoline),2,2′
-(difluoromethanediyl)-bis(8-hydroxyquinoline),bis(8-hydroxy-2-quinolinyl)methanone, 2,2′
-(1,2-ethanediyl)-bis[8-(methyloxy)quinoline],2,2′
-(1,2-ethanediyl)-bis(8-hydroxyquinoline),2,2′
-(1,2-ethanediyl)-bis(5-chloro-8-hydroxyquinoline),2,2′
-(1,2-ethanediyl)-bis(5-chloro-7-iodo-8-hydroxyquinoline),2,2′
-(1,4-butanediyl)-bis[8-(methyloxy)quinoline],2,2′
-(1,4-butanediyl)-bis(8-hydroxyquinoline),2,2′
,2″
-(1,2,3-propanetriol)-tris[8-(methyloxy)quinoline],2,2′
,2″
-(1,2,3-propanetriol)-tris(8-hydroxyquinoline),bis(8-quinolinyl)amine, N,N′
-di-8-quinolinyl-1,3-propanediamine,8,8′
-oxydiquinoline,N,N′
-bis(2-methyl-8-quinolinyl)-1,2-ethanediamine,dimethyl bis{7-(methyloxy)-8-[phenylmethyl)oxy]-2-quinolinyl}propanedioate, 2,2′
-(methanediyl)-bis(7-methyloxy-8-hydroxy-2-quinolinium) dichloride,2,2′
-(1,2-ethanediyl)-bis[7-(methyloxy)-8-quinolinol],8-hydroxy-N-(8-hydroxy-2-quinolinyl)-2-quinoline carboxamide, 2-{[8-hydroxy-2-quinolinyl)amino]methyl}-8-quinolinol, 2,2′
-(iminodimethanediyl)di(N-boc-8-quinoline amine),2,2′
-(Iminodimethanediyl)di(8-quinoline amine),2,2′
,2″
-(nitrilotrimethanediyl)tri(N-boc-8-quinoline amine),2,2′
,2″
-(nitrilotrimethanediyl)tri(8-quinoline amine),2,2′
-[(butylimino)dimethanediyl]di(N-boc-8-quinoline amine),2,2′
-[(butylimino)dimethanediyl]di(8-quinoline amine),N-butyl-2,2′
-imino-bis(8-quinoline amine),N-8-quinolinyl-8-quinoline carboxamide, and N-8-quinolinyl-8-quinoline sulfonamide, as well as the pharmaceutically acceptable stereoisomers or mixtures, tautomeric forms, hydrates, solvates, salts, free forms and esters thereof.
-
-
28. The method according to claim 26, wherein the disease is a neurodegenerative disease selected from the group consisting Alzheimer'"'"'s disease, Parkinson'"'"'s disease, Huntington'"'"'s disease, amyotrophic lateral sclerosis, Down syndrome, spongiform encephalopathies, and Creutzfeldt-Jakob'"'"'s disease.
-
29. A pharmaceutical composition comprising a compound
wherein in formula (I) X represents an — - OR, —
NRR′
, —
S(O)pR or —
OCOOR group andY represents a group of formula; in which X′
represents an —
OR, —
NRR′
, —
S(O)pR, —
OCOOR group and Z represents a group of formula -(A)m-(Alk)n-(A′
)m′
-(Alk′
)n′
-(A″
)m″
-(Alk″
)n″
, wherem, n, m′
, n′
, m″ and
n″
are the same or different and independently represent 0 or 1, it being understood that at least one of m, n, m′
, n′
m″ and
n″
is equal to 1,A, A′ and
A″
are the same or different and independently represent a group selected from —
NR—
, —
S(O)p—
, —
O— and
—
C(═
O)—
, or a 4-11 membered ring selected from cycloalkyls, heterocycles, aryls and heteroaryls, said ring being optionally substituted by one or more substituents selected from alkyl, OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
;Alk, Alk′ and
Alk″
are the same or different and independently represent an -alkyl- group, optionally substituted by one or more substituents selected from OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
; andR and R′
are the same or different and independently represent a hydrogen atom or a cycloalkyl or alkyl group, optionally substituted by one or more groups selected from OR, NRR′
, Hal, —
CN, —
CF3, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
;
heteroaryl;R1, R2, R3, R4, R5, R11, R2′
, R3, R4′
, R5′ and
R6′
are the same or different and independently represent a group or atom selected from H, OR, NRR′
, Hal, —
CN, —
CF3 and alkyl optionally substituted by one or more substituents selected from OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
;k represents 1 or 2; p represents 0, 1 or 2; as well as the pharmaceutically acceptable stereoisomers or mixtures, tautomeric forms, hydrates, solvates, salts, free forms and esters thereof, with the exception of compounds for which; X represents an —
OH group, andY represents a group of formula; in which X′
represents an —
OH group, andZ represents a group selected from —
NH—
, —
NBu-, —
NMe-, R1, R2, R3, R4, R5, R1′
, R2′
, R3′
, R4′
, R5′ and
R6′
are equal to H.- View Dependent Claims (30, 43)
dimethyl-bis[8-(acetyloxy)-2-quinoline]propanedioate, 2,2′ - -methanediyl-bis(8-hydroxyquinoline),
2,2′
-methanediyl-bis(5-chloro-8-hydroxyquinoline),2,2′
-(2,2-propanediyl)-bis(8-hydroxyquinoline),2,2′
-(2,2-propanediyl)-bis(5-chloro-8-hydroxyquinoline),2,2′
-(difluoromethanediyl)-bis(8-hydroxyquinoline),bis(8-hydroxy-2-quinolinyl)methanone, 2,2′
-(1,2-ethanediyl)-bis[8-(methyloxy)quinoline],2,2′
-(1,2-ethanediyl)-bis(8-hydroxyquinoline),2,2′
-(1,2-ethanediyl)-bis(5-chloro-8-hydroxyquinoline),2,2′
-(1,2-ethanediyl)-bis(5-chloro-7-iodo-8-hydroxyquinoline),2,2′
-(1,4-butanediyl)-bis[8-(methyloxy)quinoline],2,2′
-(1,4-butanediyl)-bis(8-hydroxyquinoline),2,2′
,2″
-(1,2,3-propanetriol)-tris[8-(methyloxy)quinoline],2,2′
,2″
-(1,2,3-propanetriol)-tris(8-hydroxyquinoline),dimethyl bis{7-(methyloxy)-8-[phenylmethyl)oxy]-2-quinolinyl}propanedioate, 2,2′
-(methanediyl)-bis(7-methyloxy-8-hydroxyquinolinium) dichloride,2,2′
-(1,2-ethanediyl)-bis[7-(methyloxy)-8-quinoline],8-hydroxy-N-(8-hydroxy-2-quinolinyl)-2-quinoline carboxamide, 2-{[8-hydroxy-2-quinolinyl)amino]methyl}-8-quinolinol, 2,2′
-(iminodimethanediyl)di(N-boc-8-quinoline amine),2,2′
-(iminodimethanediyl)di(8-quinoline amine),2,2′
,2″
-(nitrilotrimethanediyl)tri(N-boc-8-quinoline amine),2,2′
,2″
-(nitrilotrimethanediyl)tri(8-quinoline amine),2,2′
-[(butylimino)dimethanediyl]di(N-boc-8-quinoline amine),2,2′
-[(butylimino)dimethanediyl]di(8-quinoline amine), andN-butyl-2,2′
-imino-bis(8-quinoline amine),as well as the pharmaceutically acceptable stereoisomers or mixtures, tautomeric forms, hydrates, solvates, salts, free forms and esters thereof.
- OR, —
-
43. The pharmaceutical composition according to claim 29, wherein X represents OR and Y represents a group of formula (IY), in which X′
- represents OR and Z represents A, where A represents —
C(O)—
or Z represents Alk, where Alk represents a linear or branched alkyl group optionally substituted by one or more halogen atoms;
orX represents OR and Y represents a group of formula (IY), in which X′
represents OR and Z represents A-A′
, where A represents —
C(O)— and
A′
represents NR′
;
orX represents OR and Y represents a group of formula (IY), in which X′
represents OR and Z represents A-Alk, where A represents NR′ and
Alk represents a linear or branched alkyl group optionally substituted by one or more halogen atoms;
orX represents NRR′ and
Y represents a group of formula (IY), in which X′
represents NRR′ and
Z represents Alk-NR″
-Alk, where Alk represents a linear or branched alkyl group optionally substituted by one or more halogen atoms;
orX represents NRR′ and
Y represents a group of formula (IY), in which X′
represents NRR′ and
Z represents NR″
;k=1 or 2 R═
H or COOR′
or alkyl, optionally substituted, R′
═
H or alkyl, optionally substituted, R″
═
H, alkyl or heteroaryl optionally substituted and Y represents H; andR1, R2, R3, R4, R5, R1, R2′
, R3, R4′
, R5′ and
R6′
are the same or different and independently represent a group or atom selected from H, OR, NRR′
, Hal, —
CN, —
CF3 and alkyl optionally substituted by one or more substituents selected from OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
.
- represents OR and Z represents A, where A represents —
-
31. A compound of formula (I)
wherein in formula (I) X represents an — - OR, —
NRR′
, —
S(O)pR, —
OCOOR or —
NO2 group andY represents a group of formula; in which X′
represents an —
OR, —
NRR′
, —
S(O)pR, —
OCOOR or —
NO2 group andZ represents a group of formula -(A)m-(Alk)n-(A′
)m′
-(Alk′
)n′
-(A″
)m″
-(Alk″
)n″
, wherem, n, m′
, n′
, m″ and
n″
are the same or different and independently represent 0 or 1, it being understood that at least one of m, n, m′
, n′
m″ and
n″
is equal to 1,A, A′ and
A″
are the same or different and independently represent a group selected from —
NR—
, —
S(O)p—
, —
O— and
—
C(═
O)—
, or a 4-11 membered ring selected from cycloalkyls, heterocycles, aryls and heteroaryls, said ring being optionally substituted by one or more substituents selected from alkyl, OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
;Alk, Alk′ and
Alk″
are the same or different and independently represent an -alkyl- group optionally substituted by one or more substituents selected from OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR″
; andR and R′
are the same or different and independently represent a hydrogen atom or a cycloalkyl or alkyl group, optionally substituted by one or more groups selected from OR, NRR′
, Hal, —
CN, —
CF3, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR″
;
heteroaryl;R1, R2, R3, R4, R5, R11, R2′
, R3, R4′
, R5′ and
R6′
are the same or different and independently represent a group or atom selected from H, OR, NRR′
, Hal, —
CN, —
CF3 and alkyl optionally substituted by one or more substituents selected from OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
;k represents 1 or 2; p represents 0, 1 or 2; as well as the pharmaceutically acceptable stereoisomers or mixtures, tautomeric forms, hydrates, solvates, salts, free forms and esters thereof, with the exception of compounds for which; X represents an —
OH group, andY represents a group of formula; in which X′
represents an —
OH group, andZ represents a group selected from —
CH2—
, —
CH2—
CH2—
, —
(CH2)6—
, —
CH═
CH—
,—
C(Me)2-, -thienyl-, —
CH2—
S—
CH2—
, —
NH—
, —
NBu-, —
NMe-,R1, R2, R3, R4, R5, R1′
, R2′
, R3′
, R4′
, R5′ and
R6′
are equal to H.- View Dependent Claims (32, 38, 34, 35, 36, 37, 39, 40, 41)
2,2′ - -methanediyl-bis(5-chloro-8-hydroxyquinoline),
2,2′
-(2,2-propanediyl)-bis(5-chloro-8-hydroxyquinoline),2,2′
-(difluoromethanediyl)-bis(8-hydroxyquinoline),bis(8-hydroxy-2-quinolinyl)methanone, 2,2′
-(1,2-ethanediyl)-bis(5-chloro-8-hydroxyquinoline),2,2′
-(1,2-ethanediyl)-bis(5-chloro-7-iodo-8-hydroxyquinoline),2,2′
-(1,4-butanediyl)-bis[8-(methyloxy)quinoline],2,2′
-(1,4-butanediyl)-bis(8-hydroxyquinoline),2,2′
,2″
-(1,2,3-propanetriol)-tris[8-(methyloxy)quinoline],2,2′
,2″
-(1,2,3-propanetriol)-tris(8-hydroxyquinoline),dimethyl bis{7-(methyloxy)-8-[phenylmethyl)oxy]-2-quinolinyl}propanedioate, 2,2′
-(methanediyl)-bis(7-methyloxy-8-hydroxy-2-quinolinium)dichloride,2,2′
-(1,2-ethanediyl)-bis[7-(methyloxy)-8-quinolinol],8-hydroxy-N-(8-hydroxy-2-quinolinyl)-2-quinoline carboxamide, 2-{[8-hydroxy-2-quinolinyl)amino]methyl}-8-quinolinol, 2,2′
-(iminodimethanediyl)di(N-boc-8-quinoline amine),2,2′
-(iminodimethanediyl)di(8-quinoline amine),2,2′
,2″
-(nitrilotrimethanediyl)tri(N-boc-8-quinoline amine),2,2′
,2″
-(nitrilotrimethanediyl)tri(8-quinoline amine),2,2′
-[(butylimino)dimethanediyl]di(N-boc-8-quinoline amine),2,2′
-[(butylimino)dimethanediyl]di(8-quinoline amine),N-butyl-2,2′
-imino-bis(8-quinoline amine),N-butyl-2,2′
-imino-bis(8-quinoline amine),as well as the pharmaceutically acceptable stereoisomers or mixtures, tautomeric forms, hydrates, solvates, salts, free forms and esters thereof.
- OR, —
-
38. The compound according to claim 31, wherein X represents OR and Y represents a group of formula (IY), in which X′
- represents OR and Z represents A, where A represents —
C(O)—
or Z represents Alk, where Alk represents a linear or branched alkyl group optionally substituted by one or more halogen atoms;
orX represents OR and Y represents a group of formula (IY), in which X′
represents OR and Z represents A-A′
, where A represents —
C(O)— and
A′
represents NR′
;
orX represents OR and Y represents a group of formula (IY) in which X′
represents OR and Z represents A-Alk, where A represents NR′ and
Alk represents a linear or branched alkyl group optionally substituted by one or more halogen atoms;
orX represents NRR′ and
Y represents a group of formula (IY), in which X′
represents NRR′ and
Z represents Alk-NR″
-Alk, where Alk represents a linear or branched alkyl group optionally substituted by one or more halogen atoms;
orX represents NRR′ and
Y represents a group of formula (IY), in which X′
represents NRR′ and
Z represents NR″k=1 or 2 R═
H or COOR′
or alkyl, optionally substituted, R′
═
H or alkyl, optionally substituted, R″
═
H, alkyl or heteroaryl, optionally substituted, and Y represents H; andR1, R2, R3, R4, R5, R1, R2′
, R3, R4′
, R5′ and
R6′
are the same or different and independently represent a group or atom selected from H, OR, NRR′
, Hal, —
CN, —
CF3 and alkyl optionally substituted by one or more substituents selected from OR, NRR′
, CF3, Hal, CN, S(O)pR, COOR, OCOOR, CONRR′ and
NRCOOR′
.
- represents OR and Z represents A, where A represents —
-
34. A process for preparing a compound according to claim 31, comprising the stage of coupling the compounds of formula (II) and (II′
- );
followed by hydrolysis, and optionally followed by derivatisation or derivatisations of the product of formula (I) obtained in order to acquire the desired product of formula (I) and/or the stage of isolation of the product obtained.
- );
-
35. A process for preparing a compound according to claim 31, comprising the stage of coupling the compounds of formulae (III) and (III′
- );
optionally followed by derivatisation or derivatisations of the product of formula (I) obtained in order to acquire the desired product of formula (I) and/or the stage of isolation of the final product obtained.
- );
-
36. A process for preparing a compound according to claim 31, comprising the stage of coupling the compounds of formula (VII) and (VII′
- );
optionally followed by derivatisation or derivatisations of the product of formula (I) obtained in order to acquire the desired product of formula (I) and/or the isolation stage of the final product obtained.
- );
-
37. A process for preparing a compound according to claim 31, comprising the stage of coupling the compounds of formulae (VIII) and (VIII′
- );
optionally followed by derivatisation or derivatisations of the product of formula (I) obtained in order to acquire the desired product of formula (I) and/or the isolation stage of the final product obtained.
- );
-
39. A process for preparing a compound according to claim 31, comprising the stage of coupling the compounds of formula (VV) and two compounds of formula (VV′
- );
in the presence of NH3, optionally followed by derivatisation or derivatisations of the product of formula (I) obtained in order to acquire the desired product of formula (I) and/or the isolation stage of the final product obtained.
- );
-
40. A process for preparing a compound according to claim 31, comprising the stage of coupling the compounds of formulae (VVI) and (VVI′
- );
optionally followed by derivatisation or derivatisations of the product of formula (I) obtained in order to acquire the desired product of formula (I) and/or the isolation stage of the final product obtained.
- );
-
41. A process for preparing a compound according to claim 31, comprising the stage of coupling the compounds of formulae (VVII) and (VVII′
- );
in which Hal and Hal′
are halogen atoms in the presence of a group of formula—
RNH2, optionally followed by derivatisation or derivatisations of the product of formula (I) obtained in order to acquire the desired product of formula (I) and/or the isolation stage of the final product obtained.
- );
-
38-1. A process for preparing a compound according to claim 31, comprising the stage of coupling the compounds of formulae (VIII) and (VIII′
- );
in the presence of a group of formula R″
NH2 optionally followed by derivatisation or derivatisations of the product of formula (I) obtained in order to acquire the desired product of formula (I) and/or the isolation stage of the final product obtained.
- );
Specification