US2014296513A1PendingUtilityA1
Novel therapeutic use of p75 receptor antagonists
Est. expiryDec 20, 2031(~5.4 yrs left)· nominal 20-yr term from priority
A61P 3/10A61P 43/00A61P 13/10A61P 13/00A61K 31/4995A61K 31/55A61K 31/496A61K 31/46A61K 31/506
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Claims
Abstract
The present disclosure relates to the use of a p75 receptor antagonist or its pharmaceutically acceptable salts for the preparation of a medicament for use in the treatment and/or prevention of overactive bladder.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A p75 receptor antagonist for the preparation of a medicament for use in the treatment and/or prevention of overactive bladder.
2 . A p75 receptor antagonist according to claim 1 selected from:
a) a compound of general formula (I):
in which:
m (I) represents 0 or 1;
A (I) represents:
and B (I) represents a hydrogen atom;
or
A (I) represents a hydrogen atom and B (I) represents:
W (I) —is a nitrogenous heterocycle chosen from:
1-3 represents 1, 2 or 3;
n (I) represents 1 or 2;
R1 (I) represents a halogen atom, a (C 1 -C 4 )alkyl group, a trifluoromethyl radical, a (C 1 -C 4 )alkoxy group or a trifluoromethoxy radical;
R2 (I) represents a hydrogen atom, a halogen atom, a (C 1 -C 4 )alkyl group, a trifluoromethyl radical, a (C 1 -C 4 )alkoxy group, a trifluoromethoxy radical, a COOR (I) group or a CONH 2 group;
R5 (I) represents a group of formula:
in which R3 (I) and R4 (I) , located on any one of the available positions, independently represent a hydrogen atom, a halogen atom, a (C 1 -C 4 )alkyl or (C 1 -C 4 )alkoxy group, a trifluoromethyl or trifluoromethoxy radical, a cyano, or a COOH, COO(C 1 -C 4 )alkyl, CONH 2 , CONR6 (I) R7 (I) or NHCOR (I) group;
R (I) , R6 (I) and R7 (I) represent independently of each other a (C 1 -C 6 )alkyl group;
in the form of bases or of addition salts with acids;
b) a compound of general formula (II):
in which:
m (II) is 0 or 1;
A (II) is:
and B (II) is a hydrogen atom;
or
A (II) is a hydrogen atom and B (II) is:
R1 (II) and R2 (II) , which may be identical or different, are independently a hydrogen or halogen atom, a C 1 -C 4 alkyl, C 1 -C 4 fluoroalkyl, C 1 -C 2 perfluoroalkyl or C 1 -C 4 alkoxy group or a trifluoromethoxy group;
n (II) is 1 or 2;
R3 (II) is a group of formula:
where R4 (II) and R5 (II) , which may be identical or different, are located on any available positions and are independently a hydrogen or halogen atom, a hydroxyl, a C 1 -C 4 alkyl, C 1 -C 4 fluoroalkyl, C 1 -C 2 perfluoroalkyl or C 1 -C 4 alkoxy group, a trifluoromethoxy group, a cyano group, or a COOH, COOalkyl, CONH 2 , CONR6 (III) R7 (III) or NHCOR (III) group;
R (II) , R6 (II) and R7 (II) are a C 1 -C 6 alkyl group;
in the form of bases or of addition salts with acids;
c) a compound of general formula (Ill):
in which:
A (III) represents a group:
n (III) represents 1 or 2;
m (III) represents 0 or 1;
Y (III) represents a carbon, nitrogen, sulphur or oxygen atom or a single or double bond;
X (III) , X 1 (III) and X 2 (III) represent a carbon, nitrogen, sulphur or oxygen atom, it being understood that at least one of X (III) , X 1 (III) and X 2 (III) is other than a carbon atom;
R (III) and R1 (III) , located on any one of the available positions, independently represent a hydrogen atom, a halogen atom, a (C 1 -C 4 )alkyl group, a (C 1 -C 4 )alkoxy group, a perfluoroalkyl radical, a trifluoromethoxy radical, a cyano, or a COOH, COO(C 1 -C 4 )alkyl, CONR5 (III) R6 (III) or NHCOR5 (III) group;
or R1 (III) represents a group chosen from:
the definition of R (III) remaining unchanged;
R3 (III) and R4 (III) , located on any one of the available positions, independently represent a hydrogen atom, a halogen atom, a (C 1 -C 4 )alkyl group, a (C(C 1 -C 4 )—C4)alkoxy group, a perfluoroalkyl radical, a trifluoromethoxy radical, a cyano, or a COOH, COO(C 1 -C 4 )alkyl, CONR5 (III) R6 (III) or NHCOR5 (III) group;
W (III) —is a nitrogenous heterocycle chosen from:
1-2 represents 1 or 2;
1-3 represents 1, 2 or 3;
R2 (III) represents a group of formula:
R7 (III) and R8 (III) , located on any one of the available positions, independently represent a hydrogen atom, a halogen atom, a (C 1 -C 4 ))alkyl group, a (C 1 -C 4 )alkoxy group, a trifluoromethyl radical, a trifluoromethoxy radical, a cyano, or a COOH, COO(C 1 -C 4 )alkyl, COO(C 1 -C 4 )cycloalkyl, SO(C 1 -C 4 )alkyl, SO2(C 1 -C 4 )alkyl, CONH 2 , CONR5 (III) R6 (III) or NHCOR5 (III) group;
or one of R7 (III) and R8 (III) represents a heterocycle chosen from:
Z (III) represents an oxygen or sulphur atom;
R5 (III) and R6 (III) represent a hydrogen or a C1-C6 alkyl group;
in the form of bases or of addition salts with acids; and
d) a compound of general formula (IV):
in which:
n (IV) represents 1 or 2;
m (IV) represents 0 or 1;
A (IV) represents a fused heterocyclic group of formula (Y (IV) )
and B (IV) represents a hydrogen atom;
or
A (IV) represents a hydrogen atom; and
B (IV) represents a fused heterocyclic group of formula (Y (IV) )
wherein the fused heterocycle of formula Y (IV) is attached to the rest of the molecule via any of the available carbon atoms, and in which:
U (IV) completes:
either an aromatic or saturated 6-atom nucleus, containing one or two nitrogen atoms, the nucleus optionally being substituted with one or two halogen atoms, one or two (C1-C4)alkyl or (C1-C4)alkoxy groups, or one or two perfluoroalkyl radicals;
or an aromatic or saturated 5-atom nucleus, containing a nitrogen, oxygen or sulfur atom, the nucleus optionally being substituted with one or two (C1-C4)alkyl groups;
X (IV) and X1 (IV) represent independently of each other CH or N;
R (IV) and R1 (IV) located on any of the available positions, independently represent a hydrogen atom, a halogen atom, a (C 1 -C 4 )alkyl group, (C 1 -C 4 )alkoxy, a perfluoroalkyl or trifluoromethoxy radical, a cyano or a COOH, COO(C 1 -C 4 )alkyl, CONR3 (IV) R4 (IV) or NHCOR3 (IV) group;
W (IV) —bis a nitrogenous heterocycle chosen from:
1-2 represents 1 or 2;
1-3 represents 1, 2 or 3;
R2 (IV) represents a group of formula:
in which R5 (IV) and R6 (IV) , located on any of the available positions, independently represent a hydrogen atom, a halogen atom, a (C 1 -C 4 )alkyl or (C 1 -C 4 )alkoxy group, a trifluoromethyl or trifluoromethoxy radical, a cyano or a group COOH, COO(C 1 -C 4 )alkyl, COO(C 1 -C 4 )cycloalkyl, SO(C 1 -C 4 )alkyl, SO2(C 1 -C 4 )alkyl, CONR3 (IV) R4 (IV) , NR3 (IV) R4 (IV) or NHCOR3 (IV) ;
or one of the groups R5 (IV) and R6 (IV) may also represent a heterocycle chosen from:
Z (IV) represents an oxygen or sulfur atom; and
R3 (IV) and R4 (IV) represent a hydrogen or a C 1 -C 6 alkyl group;
in the form of bases or of addition salts with acids.
3 . A p75 receptor antagonist according to claim 2 selected from:
1-[4-(4-chloro-3-trifluoromethyl-phenyl)-3,6-dihydro-2H-pyridin-1-yl]-2-[8-(5-fluoro-pyrimidin-2-yl)-3,8-diaza-bicyclo[3.2.1]oct-3-yl]-ethanone;
6-{(3S,5R)-3,5-Dimethyl-4-[2-oxo-2-(2-phenyl-2,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)ethyl]piperazin-1-yl}nicotinic acid hydrochloride;
6-{(3S,5R)-4-[2-(4-benzofuran-7-yl-3,6-dihydro-2H-pyridin-1-yl)-2-oxoethyl]-3,5-dimethylpiperazin-1-yl}nicotinic acid; and
1-(2-phenyl-2,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)-2-(8-pyridin-3-yl-3,8-diazabicyclo[3.2.1]oct-3-yl)ethanone;
in the form of a base or of an addition salt with an acid.
4 . Use of a p75 receptor antagonist in the preparation of medicaments for use in the treatment and/or prevention of overactive bladder.
5 . Use according to claim 4 , wherein said p75 receptor antagonist is selected from:
a) a compound of general formula (I):
in which:
m (I) represents 0 or 1;
A (I) represents:
and B (I) represents a hydrogen atom
or
A (I) represents a hydrogen atom and B (I) represents:
W (I) —is a nitrogenous heterocycle chosen from:
1-3 represents 1, 2 or 3;
n (I) represents 1 or 2;
R1 (I) represents a halogen atom, a (C 1 -C 4 )alkyl group, a trifluoromethyl radical, a (C 1 -C 4 )alkoxy group or a trifluoromethoxy radical;
R2 (I) represents a hydrogen atom, a halogen atom, a (C 1 -C 4 )alkyl group, a trifluoromethyl radical, a (C 1 -C 4 )alkoxy group, a trifluoromethoxy radical, a COOR (I) group or a CONH 2 group;
R5 (I) represents a group of formula:
in which R3 (I) and R4 (I) , located on any one of the available positions, independently represent a hydrogen atom, a halogen atom, a (C 1 -C 4 )alkyl or (C 1 -C 4 )alkoxy group, a trifluoromethyl or trifluoromethoxy radical, a cyano, or a COOH, COO(C 1 -C 4 )alkyl, CONH 2 , CONR6 (I) R7 (I) or NHCOR (I) group;
R (I) , R6 (I) and R7 (I) represent independently of each other a (C 1 -C 6 )alkyl group;
in the form of bases or of addition salts with acids;
b) a compound of general formula (II):
in which:
m (II) is 0 or 1;
A (II) is:
and B (II) is a hydrogen atom;
or
A (II) is a hydrogen atom and B (II) is:
R1 (II) and R2 (II) , which may be identical or different, are independently a hydrogen or halogen atom, a (C 1 -C 4 )alkyl, (C 1 -C 4 ) fluoroalkyl, (C 1 -C 2 ) perfluoroalkyl or (C 1 -C 4 ) alkoxy group or a trifluoromethoxy group;
n (II) is 1 or 2;
R3 (II) is a group of formula:
where R4 (II) and R5 (II) , which may be identical or different, are located on any available positions and are independently a hydrogen or halogen atom, a hydroxyl, a (C 1 -C 4 ) alkyl, (C 1 -C 4 ) fluoroalkyl, (C 1 -C 2 ) perfluoroalkyl or (C 1 -C 4 ) alkoxy group, a trifluoromethoxy group, a cyano group, or a COOH, COO(C 1 -C 4 )alkyl, CONH 2 , CONR6 (III) R7 (III) or NHCOR (III) group;
R (II) , R6 (II) and R7 (II) are independently of each other a (C 1 -C 6 ) alkyl group;
in the form of bases or of addition salts with acids;
c) a compound of general formula (Ill):
in which:
A (III) represents a group:
n (III) represents 1 or 2;
m (III) represents 0 or 1;
Y (III) represents a carbon, nitrogen, sulphur or oxygen atom or a single or double bond;
X (III) , X 1 (III) and X 2 (III) represent a carbon, nitrogen, sulphur or oxygen atom, it being understood that at least one of X (III) , X 1 (III) and X 2 (III) is other than a carbon atom;
R (III) and R1 (III) , located on any one of the available positions, independently represent a hydrogen atom, a halogen atom, a (C 1 -C 4 )alkyl group, a (C 1 -C 4 )alkoxy group, a perfluoroalkyl radical, a trifluoromethoxy radical, a cyano, or a COOH, COO(C 1 -C 4 )alkyl, CONR5 (III) R6 (III) or NHCOR5 (III) group;
or R1 (III) represents a group chosen from:
the definition of R (III) remaining unchanged;
R3 (III) and R4 (III) , located on any one of the available positions, independently represent a hydrogen atom, a halogen atom, a (C 1 -C 4 )alkyl group, a (C(C 1 -C 4 )—C4)alkoxy group, a perfluoroalkyl radical, a trifluoromethoxy radical, a cyano, or a COOH, COO(C 1 -C 4 )alkyl, CONR5 (III) R6 (III) or NHCOR5 (III) group;
W (III) —is a nitrogenous heterocycle chosen from:
1-2 represents 1 or 2;
1-3 represents 1, 2 or 3;
R2 (III) represents a group of formula:
R7 (III) and R8 (III) , located on any one of the available positions, independently represent a hydrogen atom, a halogen atom, a (C 1 -C 4 ))alkyl group, a (C 1 -C 4 )alkoxy group, a trifluoromethyl radical, a trifluoromethoxy radical, a cyano, or a COOH, COO(C 1 -C 4 )alkyl, COO(C 1 -C 4 )cycloalkyl, SO(C 1 -C 4 )alkyl, SO2(C 1 -C 4 )alkyl, CONH 2 , CONR5 (III) R6 (III) or NHCOR5 (III) group;
or one of R7 (III) and R8 (III) represents a heterocycle chosen from:
Z (III) represents an oxygen or sulphur atom;
R5 (III) and R6 (III) represent a hydrogen or a C1-C6 alkyl group;
in the form of bases or of addition salts with acids; and
d) a compound of general formula (IV):
in which:
n (IV) represents 1 or 2;
m (IV) represents 0 or 1;
A (IV) represents a fused heterocyclic group of formula (Y (IV) )
and B (IV) represents a hydrogen atom;
or
A (IV) represents a hydrogen atom; and
B (IV) represents a fused heterocyclic group of formula (Y (IV) )
wherein the fused heterocycle of formula Y (IV) is attached to the rest of the molecule via any of the available carbon atoms, and in which:
U (IV) completes:
either an aromatic or saturated 6-atom nucleus, containing one or two nitrogen atoms, the nucleus optionally being substituted with one or two halogen atoms, one or two (C1-C4)alkyl or (C1-C4)alkoxy groups, or one or two perfluoroalkyl radicals;
or an aromatic or saturated 5-atom nucleus, containing a nitrogen, oxygen or sulfur atom, the nucleus optionally being substituted with one or two groups (C1-C4)alkyl groups;
X (IV) and X1 (IV) represent independently of each other CH or N;
R (IV) and R1 (IV) located on any of the available positions, independently represent a hydrogen atom, a halogen atom, a group (C 1 -C 4 )alkyl group, (C 1 -C 4 )alkoxy, a perfluoroalkyl or trifluoromethoxy radical, a cyano or a group COOH, COO(C 1 -C 4 )alkyl, CONR3 (IV) R4 (IV) or NHCOR3 (IV) ; group;
W (IV) —is a nitrogenous heterocycle chosen from:
1-2 represents 1 or 2;
1-3 represents 1, 2 or 3;
R2 (IV) represents a group of formula:
in which R5 (IV) and R6 (IV) , located on any of the available positions, independently represent a hydrogen atom, a halogen atom, a group (C 1 -C 4 )alkyl or (C 1 -C 4 )alkoxy group, a trifluoromethyl or trifluoromethoxy radical, a cyano or a group COOH, COO(C 1 -C 4 )alkyl, COO(C 1 -C 4 )cycloalkyl, SO(C 1 -C 4 )alkyl, SO2(C 1 -C 4 )alkyl, CONR3 (IV) R4 (IV) , NR3 (IV) R4 (IV) or NHCOR3 (IV) ;
or one of the groups R5 (IV) and R6 (IV) may also represent a heterocycle chosen from:
Z (IV) represents an oxygen or sulfur atom; and
R3 (IV) and R4 (IV) represent a hydrogen or a group C 1 -C 6 alkyl group;
in the form of bases or of addition salts with acids.
6 . Use according to claim 5 , wherein said p75 receptor antagonist is selected from:
1-[4-(4-chloro-3-trifluoromethyl-phenyl)-3,6-dihydro-2H-pyridin-1-yl]-2-[8-(5-fluoro-pyrimidin-2-yl)-3,8-diaza-bicyclo[3.2.1]oct-3-yl]-ethanone; 6-{(3S,5R)-3,5-Dimethyl-4-[2-oxo-2-(2-phenyl-2,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)ethyl]piperazin-1-yl}nicotinic acid hydrochloride; 6-{(3S,5R)-4-[2-(4-benzofuran-7-yl-3,6-dihydro-2H-pyridin-1-yl)-2-oxoethyl]-3,5-dimethylpiperazin-1-yl}nicotinic acid; and 1-(2-phenyl-2,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)-2-(8-pyridin-3-yl-3,8-diazabicyclo[3.2.1]oct-3-yl)ethanone; in the form of a base or of an addition salt with an acid.Join the waitlist — get patent alerts
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