US 9,790,201 B2Granted

Piperidine and azepine derivatives as prokineticin receptor modulators

AssigneeTakeda Pharmaceutical Company Limited

InventorsSarah Bousba, Anne Goldby, Kerry Jenkins, Natasha Kinsella, Martin Teall

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Abstract

The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof (Formula (I)) in which m, X, R1, R2, R3 and R5 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.

Claims23

Dependent claims

A compound of formula

wherein
R1 represents a C5-C10 aryl group which is optionally substituted by at least one substituent independently selected from halogen, hydroxyl, cyano, oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 alkylsulphinyl, C1-C6 alkylsulphonyl, C1-C6 alkylcarbonyl, C1-C6 alkylcarbonyloxy, C1-C6 alkoxycarbonyl, —NR6R7, —CONR8R9, C3-C6 cycloalkyl, C3-C6 cycloalkyloxy or C3-C6 cycloalkylmethyl;
R2 represents a hydrogen or fluorine atom or a hydroxyl, C1-C3 alkoxy or trifluoromethoxy group and R3 represents a hydrogen atom, or R2 and R3 may together form a carbon-carbon bond;
X represents a group CHR4;
R4 represents a hydrogen atom or, when R3 represents a hydrogen atom, R4 may together with R2 form a carbon-carbon bond;
m is 1 or 2;
R5 represents a 5- to 6-membered heteroaryl group comprising a pyrindinyl group, a pyridazninyl group or a pyrazolyl group, the heteroaryl group being optionally substituted by at least one substituent independently selected from halogen, cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylsulphinyl, C1-C6 alkylsulphonyl, C1-C6 alkylcarbonyl, C1-C6 alkylcarbonyloxy, C1-C6 alkoxycarbonyl, —NR10R11, —CONR12R13, C3-C6 cycloalkyl, C3-C6 cycloalkyloxy or C3-C6 cycloalkylmethyl;
R6 and R7 each independently represent a hydrogen atom or a C1-C6 alkyl or C3-C6 cycloalkyl group, or R6 and R7 may together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring optionally substituted by halogen or hydroxy;
R8 and R9 each independently represent a hydrogen atom or a C1-C6 alkyl group, or R8 and R9 may together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
R10 and R11 each independently represent a hydrogen atom or a C1-C6 alkyl or C3-C6 cycloalkyl group, or R10 and R11 may together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring optionally substituted by halogen or hydroxy;
and
R12 and R13 each independently represent a hydrogen atom or a C1-C6 alkyl group, or R12 and R13 may together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
provided that the compound of formula (I) is not:
(3-(4-chlorophenyl)-1-piperidinyl)(1-methyl-3-propyl-1H-pyrazol-5-yl)methanone,
(6-amino-3-pyridinyl)(3-(2-methylphenyl)-1-piperidinyl)methanone,
(2-amino-4-pyridinyl)(3-(2-methylphenyl)-1-piperidinyl)methanone,
[1-ethyl-3-(1-methyethyl)-1H-pyrazol-5-yl][3-(2-methylphenyl)-1-piperidinyl]methanone,
[3-(3-methylphenyl)-1-piperidinyl](1-methyl-3-propyl-1H-pyrazol-5-yl)methanone,
[3-(3-methylphenyl)-1-piperidinyl]-2-pyridinyl-methanone,
5-[[3-(2-methylphenyl)-1-piperidinyl]carbonyl]-2-pyridinecarbonitrile,
(2-methoxy-3-pyridinyl)[3-(3-methylphenyl)-1-piperidinyl]methanone,
[3-(2-methylphenyl)-1-piperidinyl](3-propyl-1H-pyrazol-4-yl)methanone,
(1-ethyl-1H-pyrazol-4-yl)[3-(3-methylphenyl)-1-piperidinyl]methanone,
[1-(1-methylethyl)-1H-pyrazol-4-yl](3-phenyl-1-piperidinyl)methanone, or
[3-hydroxy-3-(2-methoxyphenyl)-1-piperidinyl][1-(1-methylethyl)-1H-pyrazol-5-yl]methanone;
or a pharmaceutically acceptable salt thereof.

23 more elements

A compound being selected from:

4-{[3-(2-Fluorophenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
4-{[3-(2,4-Dichlorophenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
4-{[3-(4-Chlorophenyl)piperidin-1-yl]carbonyl}-2-cyclopropylpyridine,
4-{[3-(4-Chloro-2-methylphenyl)piperidin-1-yl]carbonyl}-2-ethylpyridine,
4-{[3-(4-Chloro-2-methylphenyl)piperidin-1-yl]carbonyl}-2-methylpyridine,
4-({3-[4-Chloro-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-2-ethylpyridine,
4-({3-[4-Chloro-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-N,N-dimethylpyridin-2-amine,
4-{[3-(4-Chlorophenyl)piperidin-1-yl]carbonyl}-N-(propan-2-yl)pyridin-2-amine,
4-({3-[4-Chloro-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-2-methoxypyridine,
4-({3-[4-Chloro-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-2-methylpyridine,
N-Methyl-4-{[3-(4-methylphenyl)piperidin-1-yl]carbonyl}pyridin-2-amine,
2-Methyl-4-{[3-(4-methylphenyl)piperidin-1-yl]carbonyl}pyridine,
N,N-Dimethyl-4-{[3-(3-methylphenyl)piperidin-1-yl]carbonyl}pyridin-2-amine,
N,N-Dimethyl-4-{[3-(2-methylphenyl)piperidin-1-yl]carbonyl}pyridin-2-amine,
N,N-Dimethyl-4-[(3-phenylpiperidin-1-yl)carbonyl]pyridin-2-amine,
4-{[3-(4-Chlorophenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
4-{[(3 S)-3-(4-Chlorophenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
4-{[(3R)-3-(4-Chlorophenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
4-{[3-(4-Fluorophenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
2-Ethyl-4-{[3-(4-methylphenyl)piperidin-1-yl]carbonyl}pyridine,
2-(Azetidin-1-yl)-4-{[3-(4-methylphenyl)piperidin-1-yl]carbonyl}pyridine,
2-(Azetidin-1-yl)-4-{[3-(4-chlorophenyl)piperidin-1-yl]carbonyl}pyridine,
2-(Azetidin-1-yl)-4-{[3-(2-methylphenyl)piperidin-1-yl]carbonyl}pyridine,
4-{[3-(4-Chloro-2-methylphenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
4-{[3-(4-Chloro-2-fluorophenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
4-{[3-(2-Chloro-4-fluorophenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
4-{[3-(4-Chlorophenyl)piperidin-1-yl]carbonyl}-N-methylpyridin-2-amine,
4-{[3-(4-Chlorophenyl)piperidin-1-yl]carbonyl}-2,6-dimethylpyridine,
2-Chloro-4-{[3-(4-chlorophenyl)piperidin-1-yl]carbonyl}pyridine,
4-{[3-(4-Chlorophenyl)piperidin-1-yl]carbonyl}-2-(propan-2-yl)pyridine,
4-{[3-(4-Chloro-2-methylphenyl)piperidin-1-yl]carbonyl}-N-methylpyridin-2-amine,
4-{[3-(4-Chloro-2-methylphenyl)piperidin-1-yl]carbonyl}-2-methoxypyridine,
2-(Azetidin-1-yl)-4-{[3-(4-chloro-2-methylphenyl)piperidin-1-yl]carbonyl}pyridine,
2-Methoxy-4-{[3-(4-methylphenyl)piperidin-1-yl]carbonyl}pyridine,
4-{[3-(4-Methylphenyl)piperidin-1-yl]carbonyl}-2-(pyrrolidin-1-yl)pyridine,
4-{[(3S)-3-(3-Methoxyphenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
N-Ethyl-N-methyl-4-{[3-(4-methylphenyl)piperidin-1-yl]carbonyl}pyridin-2-amine,
2-(3,3-Difluoroazetidin-1-yl)-4-{[3-(4-methylphenyl)piperidin-1-yl]carbonyl}pyridine,
N-Methyl-4-{[3-(4-methylphenyl)piperidin-1-yl]carbonyl}-N-propylpyridin-2-amine,
N-Methyl-4-{[3-(4-methylphenyl)piperidin-1-yl]carbonyl}-N-(propan-2-yl)pyridin-2-amine,
1-(4-{[3-(4-Methylphenyl)piperidin-1-yl]carbonyl}pyridin-2-yl)azetidin-3-ol,
4-{[3-(4-Chlorophenyl)piperidin-1-yl]carbonyl}-2-ethoxypyridine,
N-Cyclopropyl-N-methyl-4-{[3-(4-methylphenyl)piperidin-1-yl]carbonyl}pyridin-2-amine,
N,N-Dimethyl-4-({3-[4-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)pyridin-2-amine,
N,N-Dimethyl-4-({3-[2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)pyridin-2-amine,
4-{[3-(2-Chlorophenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
4-{[3-(4-Methoxyphenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
4-{[3-(2-Methoxyphenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
N,N-Dimethyl-4-{[3-(4-methylphenyl)piperidin-1-yl]carbonyl}pyridin-2-amine,
N,N-Dimethyl-4-{[3-(4-methylphenyl)piperidin-1-yl]carbonyl}pyridin-2-amine (R Enantiomer),
N,N-Dimethyl-4-{[3-(4-methylphenyl)piperidin-1-yl]carbonyl}pyridin-2-amine (S Enantiomer),
4-{[3-(4-Chlorophenyl)piperidin-1-yl]carbonyl}-2-ethylpyridine,
N-Methyl-4-({3-[4-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)pyridin-2-amine,
N-Methyl-4-({3-[2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)pyridin-2-amine,
4-{[3-(4-Methoxyphenyl)piperidin-1-yl]carbonyl}-N-methylpyridin-2-amine,
4-{[3-(2-Methoxyphenyl)piperidin-1-yl]carbonyl}-N-methylpyridin-2-amine,
4-({3-[4-Chloro-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-N-methylpyridin-2-amine,
2-Ethyl-4-({3-[2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)pyridine,
2-Ethyl-4-{[3-(2-methoxyphenyl)piperidin-1-yl]carbonyl}pyridine,
N,N-Dimethyl-4-({3-[2-(trifluoromethoxy)phenyl]piperidin-1-yl}carbonyl)pyridin-2-amine,
4-{[3-(4-Chloro-2-ethoxyphenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
4-({3-[4-Methoxy-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-N,N-dimethylpyridin-2-amine,
4-{[3-(4-Methoxy-2-methylphenyl)piperidin-1-yl]carbonyl}-N-methylpyridin-2-amine,
4-({3-[4-Methoxy-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-N-methylpyridin-2-amine,
4-{[3-(4-Chloro-2-ethoxyphenyl)piperidin-1-yl]carbonyl}-N-methylpyridin-2-amine,
4-({3-[2-(Difluoromethoxy)phenyl]piperidin-1-yl}carbonyl)-N,N-dimethylpyridin-2-amine,
2-(1-{[2-(Dimethylamino)pyridin-4-yl]carbonyl}piperidin-3-yl)benzonitrile,
4-{[3-(4-Chloro-2,6-dimethylphenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
5-{[3-(4-Chlorophenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridazin-3-amine,
5-{[3-(4-Chloro-2-methylphenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridazin-3-amine,
5-{[3-(4-Chloro-2-methylphenyl)piperidin-1-yl]carbonyl}-N-methylpyridazin-3-amine,
5-{[(3R)-3-(4-Chloro-2-methylphenyl)piperidin-1-yl]carbonyl}-N-methylpyridazin-3-amine,
5-{[(3S)-3-(4-Chloro-2-methylphenyl)piperidin-1-yl]carbonyl}-N-methylpyridazin-3-amine,
5-{[3-(4-Chloro-2-methylphenyl)piperidin-1-yl]carbonyl}-3-methoxypyridazine,
5-({3-[4-Chloro-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-N,N-dimethylpyridazin-3-amine,
5-({3-[4-Chloro-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-N-methylpyridazin-3-amine,
3-(Azetidin-1-yl)-5-({3-[4-chloro-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)pyridazine,
5-({3-[2-Methoxy-4-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-N-methylpyridazin-3-amine,
5-{[3-(4-Methoxy-2-methylphenyl)piperidin-1-yl]carbonyl}-N-methylpyridazin-3-amine,
5-{[3-(4-Methoxy-2-methylphenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridazin-3-amine,
5-({3-[4-Methoxy-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-N-methylpyridazin-3-amine,
5-({3-[4-Methoxy-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-N,N-dimethylpyridazin-3-amine,
5-{[3-(4-Chloro-2-ethoxyphenyl)piperidin-1-yl]carbonyl}-N-methylpyridazin-3-amine,
5-{[3-(4-Chloro-2-ethoxyphenyl)piperidin-1-yl]carbonyl}-N,N-dimethylpyridazin-3-amine,
5-{[3-(4-Chloro-2-methylphenyl)piperidin-1-yl]carbonyl}-3-methylpyridazine,
5-{[3-(2-Methoxyphenyl)piperidin-1-yl]carbonyl}-N-methylpyridazin-3-amine,
3-(4-Chloro-2-methylphenyl)-1-[(1,3-dimethyl-1H-pyrazol-4-yl)carbonyl]piperidine,
3-(4-Chlorophenyl)-1-[(1,3-dimethyl-1H-pyrazol-4-yl)carbonyl]piperidine,
3-(4-Chlorophenyl)-1-[(1-methyl-1H-pyrazol-4-yl)carbonyl]piperidine,
3-(4-Chlorophenyl)-1-[(1-ethyl-1H-pyrazol-4-yl)carbonyl]piperidine,
3-(4-Chlorophenyl)-1-{[1-(propan-2-yl)-1H-pyrazol-4-yl]carbonyl}piperidine,
3-(4-Chloro-2-methylphenyl)-1-[(1-ethyl-1H-pyrazol-4-yl)carbonyl]piperidine,
3-(4-Chloro-2-methylphenyl)-1-{[1-(propan-2-yl)-1H-pyrazol-4-yl]carbonyl}piperidine,
3-(4-Chloro-2-methylphenyl)-1-[(1-methyl-1H-pyrazol-4-yl)carbonyl]piperidine,
4-{[3-(4-Chloro-2-methylphenyl)piperidin-1-yl]carbonyl}-1-methyl-1H-pyrazol-5-amine,
3-[4-Chloro-2-(trifluoromethyl)phenyl]-1-[(1H-pyrazol-4-yl)carbonyl]piperidine,
3-[4-Chloro-2-(trifluoromethyl)phenyl]-1-[(1-methyl-1H-pyrazol-4-yl)carbonyl]piperidine,
3-[4-Chloro-2-(trifluoromethyl)phenyl]-1-[(1-ethyl-1H-pyrazol-4-yl)carbonyl]piperidine,
3-[4-Chloro-2-(trifluoromethyl)phenyl]-1-{[1-(propan-2-yl)-1H-pyrazol-4-yl]carbonyl}piperidine,
4-({3-[4-Chloro-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-1-methyl-1H-pyrazol-3-amine,
1-[(1,3-Dimethyl-1H-pyrazol-4-yl)carbonyl]-3-(4-methoxy-2-methylphenyl)piperidine,
4-{[3-(4-Methoxy-2-methylphenyl)piperidin-1-yl]carbonyl}-1-methyl-1H-pyrazol-3-amine,
3-[4-Chloro-2-(trifluoromethyl)phenyl]-1-[(1,3-dimethyl-1H-pyrazol-4-yl)carbonyl]piperidine,
4-{[5-(4-Chlorophenyl)-1,2,3,4-tetrahydropyridin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
4-{[5-(4-Chloro-2-methylphenyl)-1,2,3,4-tetrahydropyridin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
4-{[5-(2,4-Dichlorophenyl)-1,2,3,4-tetrahydropyridin-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
N,N-Dimethyl-4-[(3-phenylazepan-1-yl)carbonyl]pyridin-2-amine,
4-{[3-(4-Chlorophenyl)azepan-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
4-{[3-(4-Methoxyphenyl)azepan-1-yl]carbonyl}-N,N-dimethylpyridin-2-amine,
4-{[3-(4-Methoxyphenyl)azepan-1-yl]carbonyl}-N-methylpyridin-2-amine,
4-{[3-(4-Chlorophenyl)azepan-1-yl]carbonyl}-N-methylpyridin-2-amine,
5-{[3-(4-Methoxyphenyl)azepan-1-yl]carbonyl}-N-methylpyridazin-3-amine,
5-{[3-(4-Chlorophenyl)azepan-1-yl]carbonyl}-N-methylpyridazin-3-amine,
5-{[3-(4-Methoxyphenyl)azepan-1-yl]carbonyl}-N,N-dimethylpyridazin-3-amine,
5-{[3-(4-Chlorophenyl)azepan-1-yl]carbonyl}-N,N-dimethylpyridazin-3-amine,
3-(4-Chloro-2-methylphenyl)-1-{[2-(dimethylamino)pyridin-4-yl]carbonyl}piperidin-3-ol,
1-{[2-(Dimethylamino)pyridin-4-yl]carbonyl}-3-(4-fluorophenyl)piperidin-3-ol,
4-({3-[4-Chloro-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-1-methyl-1H-pyrazol-3-amine (R Enantiomer),
4-({3-[4-Chloro-2-(trifluoromethyl)phenyl]piperidin-1-yl}carbonyl)-1-methyl-1H-pyrazol-3-amine (S Enantiomer),
and pharmaceutically acceptable salts thereof.

117 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/910,377Filed 7 Aug 2014
Priority: GB 1314286.48 Aug 2013
Published: US 2016/0185752 A130 Jun 2016
Granted: 17 Oct 2017
Term ends: Not estimatedThe source records don’t support an estimate.

Classification15 codes

C07D 401/06
Containing two hetero rings: linked by a carbon chain containing only aliphatic carbon atoms
A61K 31/454
Containing further heterocyclic ring systems: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4545
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/501
Pyridazines; Hydrogenated pyridazines: not condensed and containing further heterocyclic rings

Family

US 2016/0185752 A1Pre-grant publication · published 30 Jun 2016
US 9,790,201 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of formula

wherein
R1 represents a C5-C10 aryl group which is optionally substituted by at least one substituent independently selected from halogen, hydroxyl, cyano, oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 alkylsulphinyl, C1-C6 alkylsulphonyl, C1-C6 alkylcarbonyl, C1-C6 alkylcarbonyloxy, C1-C6 alkoxycarbonyl, —NR6R7, —CONR8R9, C3-C6 cycloalkyl, C3-C6 cycloalkyloxy or C3-C6 cycloalkylmethyl;
R2 represents a hydrogen or fluorine atom or a hydroxyl, C1-C3 alkoxy or trifluoromethoxy group and R3 represents a hydrogen atom, or R2 and R3 may together form a carbon-carbon bond;
X represents a group CHR4;
R4 represents a hydrogen atom or, when R3 represents a hydrogen atom, R4 may together with R2 form a carbon-carbon bond;
m is 1 or 2;
R5 represents a 5- to 6-membered heteroaryl group comprising a pyrindinyl group, a pyridazninyl group or a pyrazolyl group, the heteroaryl group being optionally substituted by at least one substituent independently selected from halogen, cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylsulphinyl, C1-C6 alkylsulphonyl, C1-C6 alkylcarbonyl, C1-C6 alkylcarbonyloxy, C1-C6 alkoxycarbonyl, —NR10R11, —CONR12R13, C3-C6 cycloalkyl, C3-C6 cycloalkyloxy or C3-C6 cycloalkylmethyl;
R6 and R7 each independently represent a hydrogen atom or a C1-C6 alkyl or C3-C6 cycloalkyl group, or R6 and R7 may together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring optionally substituted by halogen or hydroxy;
R8 and R9 each independently represent a hydrogen atom or a C1-C6 alkyl group, or R8 and R9 may together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
R10 and R11 each independently represent a hydrogen atom or a C1-C6 alkyl or C3-C6 cycloalkyl group, or R10 and R11 may together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring optionally substituted by halogen or hydroxy;
and
R12 and R13 each independently represent a hydrogen atom or a C1-C6 alkyl group, or R12 and R13 may together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring;
provided that the compound of formula (I) is not:
(3-(4-chlorophenyl)-1-piperidinyl)(1-methyl-3-propyl-1H-pyrazol-5-yl)methanone,
(6-amino-3-pyridinyl)(3-(2-methylphenyl)-1-piperidinyl)methanone,
(2-amino-4-pyridinyl)(3-(2-methylphenyl)-1-piperidinyl)methanone,
[1-ethyl-3-(1-methyethyl)-1H-pyrazol-5-yl][3-(2-methylphenyl)-1-piperidinyl]methanone,
[3-(3-methylphenyl)-1-piperidinyl](1-methyl-3-propyl-1H-pyrazol-5-yl)methanone,
[3-(3-methylphenyl)-1-piperidinyl]-2-pyridinyl-methanone,
5-[[3-(2-methylphenyl)-1-piperidinyl]carbonyl]-2-pyridinecarbonitrile,
(2-methoxy-3-pyridinyl)[3-(3-methylphenyl)-1-piperidinyl]methanone,
[3-(2-methylphenyl)-1-piperidinyl](3-propyl-1H-pyrazol-4-yl)methanone,
(1-ethyl-1H-pyrazol-4-yl)[3-(3-methylphenyl)-1-piperidinyl]methanone,
[1-(1-methylethyl)-1H-pyrazol-4-yl](3-phenyl-1-piperidinyl)methanone, or
[3-hydroxy-3-(2-methoxyphenyl)-1-piperidinyl][1-(1-methylethyl)-1H-pyrazol-5-yl]methanone;
or a pharmaceutically acceptable salt thereof.

23 more elements

Facts

Application

14/910,377Filed 7 Aug 2014

Priority

GB 1314286.48 Aug 2013

Published

US 2016/0185752 A130 Jun 2016

Granted

17 Oct 2017

Term ends

Not estimatedThe source records don’t support an estimate.

Classification15 codes

C07D 401/06
Containing two hetero rings: linked by a carbon chain containing only aliphatic carbon atoms
A61K 31/454
Containing further heterocyclic ring systems: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4545
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/501
Pyridazines; Hydrogenated pyridazines: not condensed and containing further heterocyclic rings