IP Library Granted Patent US 9,718,774
Granted Patent B2
US 9,718,774 · App. 14/651,922 · Granted Aug 1, 2017

Indole carboxamide derivatives as P2X7 receptor antagonist

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Quick Facts
Patent No.
US 9,718,774
App. No.
14/651,922
Granted
Aug 1, 2017
Kind
B2
Abstract

The invention relates to indole carboxamide derivatives of formula (I), wherein R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined in the description, their preparation and their use as pharmaceutically active compounds.

Claims (203)

1. A compound of the formula (I),

wherein

R 1 represents a heteroaryl or an aryl group which groups are independently unsubstituted, mono-, di-, or tri-substituted, wherein the substituents are independently selected from the group consisting of (C 1 -C 4 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 4 )alkoxy, (C 1 -C 3 )fluoroalkyl, (C 1 -C 3 )fluoroalkoxy, hydroxy, halogen and phenoxy;

R 2 represents

heterocyclyl which is unsubstituted, mono- or di-substituted, wherein the substituents are independently selected from (C 1 -C 4 )alkyl, (C 1 -C 4 )alkylcarbonyl, (C 1 -C 4 )alkoxycarbonyl, (C 1 -C 4 )alkylsulfonyl, and halogen;

heterocyclyloxy;

(C 3 -C 6 )cycloalkyl which is unsubstituted or mono- or di-substituted with halogen;

(C 3 -C 6 )cycloalkyloxy;

N—(C 3 -C 6 )cycloalkyl-amino;

N—(C 3 -C 6 )cycloalkylmethyl-amino;

(C 3 -C 6 )alkyl;

(C 2 -C 6 )alkoxy;

N—(C 1 -C 4 )alkylamino;

N,N-di-[(C 1 -C 4 )alkyl]-amino; or

N-arylmethyl-N—(C 1 -C 4 )alkyl-amino;

R 3 represents hydrogen or halogen;

R 4 represents hydrogen, fluoro, chloro, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, (C 1 -C 4 )alkyl-carbonyl, hydroxy-(C 1 -C 4 )alkyl, hydroxy-(C 2 -C 4 )alkoxy, (C 1 -C 2 )alkoxy-(C 1 -C 4 )alkyl or (C 1 -C 4 )alkoxy -(C 2 -C 4 )alkoxy;

R 5 represents hydrogen or (C 1 -C 4 )alkyl; and

R 6 represents fluoro, chloro, methyl, ethyl or (C 1 -C 2 )fluoroalkyl;

or a salt of such a compound.

2. The compound of formula (I) according to claim 1 , wherein

R 1 represents a 5- or 6-membered monocyclic heteroaryl group which is unsubstituted, mono- or di-substituted, wherein the substituents are independently selected from the group consisting of (C 1 -C 4 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 4 )alkoxy, (C 1 -C 3 )fluoroalkyl and halogen;

R 2 represents

heterocyclyl which is unsubstituted, mono- or di-substituted, wherein the substituents are independently selected from methyl and fluoro; or

(C 3 -C 6 )cycloalkyl which is unsubstituted or mono- or di-substituted with fluoro;

R 3 represents hydrogen;

R 4 represents hydrogen or (C 1 -C 4 )alkyl;

R 5 represents hydrogen; and

R 6 represents chloro or methyl;

or a salt of such a compound.

3. The compound of formula (I) according to claim 1 , wherein

R 1 represents a 5- or 6-membered monocyclic heteroaryl or a phenyl group which groups are independently unsubstituted, mono- or di-substituted, wherein the substituents are independently selected from the group consisting of (C 1 -C 4 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 3 )fluoroalkyl and halogen;

or a salt of such a compound.

4. The compound of formula (I) according to claim 2 , wherein

R 2 represents heterocyclyl which is unsubstituted or mono- or di-substituted with fluoro;

or a salt of such a compound.

5. The compound of formula (I) according to claim 3 , wherein

R 2 represents (C 3 -C 6 )alkyl; or (C 3 -C 6 )cycloalkyl which is unsubstituted or mono- or di-substituted with fluoro;

or a salt of such a compound.

6. The compound of formula (I) according to claim 1 , which is also a compound of formula (I Ar )

wherein

A represents N or CH;

B represents N or CH;

R 2 represents heterocyclyl which is unsubstituted or mono- or di-substituted with fluoro, wherein the heterocyclyl is selected from pyrrolidinyl, piperidinyl, tetrahydropyranyl, morpholinyl, azepanyl, 1,4-oxazepanyl and 6-oxa-3-azabicyclo[3.1.1]heptanyl; or

R 2 represents cyclohexyl which is unsubstituted or mono- or di-substituted with fluoro;

R 4 represents hydrogen, fluoro, chloro, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, hydroxy-(C 2 -C 4 )alkoxy or (C 1 -C 2 )alkoxy-(C 1 -C 4 )alkyl;

R 6 represents fluoro, chloro, methyl, ethyl or (C 1 -C 2 )fluoroalkyl; and

R 7 represents hydrogen, halogen, (C 1 -C 4 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 4 )alkoxy or (C 1 -C 3 )fluoroalkyl;

or a salt of such a compound.

7. The compound of formula (I Ar ) according to claim 6 , wherein

A and B represent N and R 7 represents hydrogen, methyl, cyclopropyl or trifluoromethyl; or

A represents N, B represents CH and R 7 represents chloro, methyl, methoxy or trifluoromethyl; or

A and B represent CH and R 7 represents fluoro or chloro;

R 2 represents 3,3-difluoro-pyrrolidin-1-yl, piperidin-1-yl, 4-fluoro-piperidin-1-yl, 3,3-difluoro-piperidin-1-yl, 4,4-difluoro-piperidin-1-yl, tetrahydropyran-4-yl, morpholin-4-yl, azepan-1-yl, 1,4-oxazepan-4-yl, or 6-oxa-3-azabicyclo[3.1.1]heptan-3-yl;

R 4 represents hydrogen, chloro, methyl, ethyl, n-propyl, iso-butyl, methoxy, ethoxy, 2-hydroxy-ethoxy or 3-methoxy-prop-1-yl;

R 6 represents fluoro, chloro, methyl, ethyl or trifluoromethyl;

or a salt of such a compound.

8. The compound of formula (I Ar ) according to claim 6 , wherein

A and B represent N;

or a salt of such a compound.

9. The compound of formula (I) according to claim 1 , wherein

R 6 represents chloro;

or a salt of such a compound.

10. The compound of formula (I) according to claim 1 , wherein

R 6 represents methyl;

or a salt of such a compound.

11. The compound of formula (I) according to claim 1 , selected from the group consisting of:

4-Chloro-1H-indole-5-carboxylic acid [2-morpholin-4-yl-2-(2-trifluoromethyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(6-chloro-pyridin-3-yl)-2-(4,4-difluoro-piperidin-1-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [(R)-2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [(S)-2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [(R)-2-(4,4-difluoro-piperidin-1-yl)-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [(S)-2-(4,4-difluoro-piperidin-1-yl)-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(6-methyl-pyridin-3-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(4,4-difluoro-piperidin-1-yl)-2-(2-trifluoromethyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(2-cyclopropyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-morpholin-4-yl-2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(6-methoxy-pyridin-3-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-dimethylamino-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-azetidin-1-yl-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-pyrrolidin-1-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-diethylamino-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-piperidin-1-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(4-fluoro-phenyl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(3,5-difluoro-phenyl)-2-morpholin-4-yl-ethyl]-amide;

4-{2-[(4-Chloro-1H-indole-5-carbonyl)-amino]-1-pyridin-3-yl-ethyl}-piperidine-1-carboxylic acid tert-butyl ester;

4-Chloro-1H-indole-5-carboxylic acid (2-piperidin-4-yl-2-pyridin-3-yl-ethyl)-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(1-methyl-piperidin-4-yl)-2-pyridin-3-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(1-acetyl-piperidin-4-yl)-2-pyridin-3-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(1-methanesulfonyl-piperidin-4-yl)-2-pyridin-3-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(6-chloro-pyridin-3-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid (2-morpholin-4-yl-2-pyridin-3-yl-ethyl)-amide;

4-Chloro-1H-indole-5-carboxylic acid (2-morpholin-4-yl-2-pyrimidin-5-yl-ethyl)-amide;

4-Chloro-1H-indole-5-carboxylic acid (2-piperidin-1-yl-2-pyrimidin-5-yl-ethyl)-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(1-methyl-1H-pyrazol-4-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(1-methyl-1H-pyrazol-4-yl)-2-piperidin-1-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-piperidin-1-yl-2-(2,4,6-trifluoro-phenyl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(2,4-difluoro-phenyl)-2-piperidin-1-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(5-fluoro-pyridin-2-yl)-2-piperidin-1-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-morpholin-4-yl-2-(2,4,6-trifluoro-phenyl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(2,4-difluoro-phenyl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(2-fluoro-phenyl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(5-fluoro-pyridin-2-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(3-fluoro-phenyl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(4-chloro-phenyl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(2,4-dichloro-phenyl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(4-chloro-2-fluoro-phenyl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(cis-2,6-dimethyl-morpholin-4-yl)-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(trans-2,6-dimethyl-morpholin-4-yl)-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(3-fluoro-phenyl)-2-piperidin-1-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-piperidin-1-yl-2-(4-trifluoromethyl-phenyl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(3,4-difluoro-phenyl)-2-piperidin-1-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid (2-piperidin-1-yl-2-pyridin-3-yl-ethyl)-amide;

4-Chloro-1H-indole-5-carboxylic acid (2-morpholin-4-yl-2-p-tolyl-ethyl)-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-morpholin-4-yl-2-(4-trifluoromethoxy-phenyl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-morpholin-4-yl-2-(4-trifluoromethyl-phenyl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(3,4-difluoro-phenyl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-(tetrahydro-pyran-4-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-cyclopentyloxy-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(3,5-dimethyl-isoxazol-4-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(3,5-dimethyl-isoxazol-4-yl)-2-piperidin-1-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid (2-piperidin-1-yl-2-p-tolyl-ethyl)-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(6-chloro-pyridin-3-yl)-2-piperidin-1-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(4-phenoxy-phenyl)-2-piperidin-1-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-morpholin-4-yl-2-(4-phenoxy-phenyl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(4-methoxy-phenyl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(5-methyl-pyrazin-2-yl)-2-piperidin-1-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid (2-isothiazol-5-yl-2-piperidin-1-yl-ethyl)-amide;

4-Chloro-1H-indole-5-carboxylic acid (2-piperidin-1-yl-2-thiazol-5-yl-ethyl)-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(5-methyl-pyrazin-2-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid (2-morpholin-4-yl-2-thiazol-5-yl-ethyl)-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(6-chloro-pyridin-3-yl)-2-cyclohexyl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(6-chloro-pyridin-3-yl)-4-methyl-pentyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-ethoxy-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-(2-oxa-5-azabicyclo[2.2.1]hept-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-cyclohexyloxy-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-(tetrahydro-pyran-4-yloxy)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(1-ethyl-propoxy)-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-2-methyl-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid (2-piperidin-1-yl-2-pyridazin-3-yl-ethyl)-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(2-hydroxypyridin-4-yl)-2-piperidin-1-yl-ethyl]-amide;

1-[2-[(4-Chloro-1H-indole-5-carbonyl)-amino]-1-(2-methyl-pyrimidin-5-yl)-ethyl]-piperidine-4-carboxylic acid tert-butyl ester;

4-Chloro-1H-indole-5-carboxylic acid [2-(4-methyl-piperidin-1-yl)-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [(R)-2-(2-methyl-piperidin-1-yl)-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(4-fluoro-piperidin-1-yl)-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(3,3-difluoro-piperidin-1-yl)-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-azepan-1-yl-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-[1,4]oxazepan-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(3,3-difluoro-pyrrolidin-1-yl)-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-cyclopentylamino-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(cyclopentylmethyl-amino)-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-isobutylamino-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(isobutyl-methyl-amino)-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(benzyl-methyl-amino)-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid (3-ethyl-2-pyrimidin-5-yl-pentyl)-amide;

4-[2-[(4-Chloro-1H-indole-5-carbonyl)-amino]-1-(2-methyl-pyrimidin-5-yl)-ethyl]-piperazine-1-carboxylic acid tert-butyl ester;

4-Chloro-1H-indole-5-carboxylic acid (2-morpholin-4-yl-2-pyridazin-3-yl-ethyl)-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-morpholin-4-yl-2-(2-hydroxypyridin-4-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(1,1-dioxo-thiomorpholin-4-yl)-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(4,4-difluoro-cyclohexyl)-2-(2-methyl-pyrimidin-5-yl)-ethyl]-amide;

4,6-Dichloro-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-(6-oxa-3-azabicyclo[3.1.1]hept-3-yl)-ethyl]-amide;

4-Chloro-7-methyl-1H-indole-5-carboxylic acid [(R)-2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-7-methyl-1H-indole-5-carboxylic acid [(S)-2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-7-isobutyl-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-7-(3-methoxy-propyl)-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Methyl-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Ethyl-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

7-Acetyl-4-chloro-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

7-Methyl-4-trifluoromethyl-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4,7-Dimethyl-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Methyl-1H-indole-5-carboxylic acid [(S)-2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Methyl-1H-indole-5-carboxylic acid [(R)-2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-7-ethyl-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

7-Chloro-4-methyl-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

7-Methoxy-4-methyl-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-7-ethoxy-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-7-propyl-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

7-(2-tert-Butoxy-ethoxy)-4-chloro-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-7-(2-hydroxy-ethoxy)-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-7-methoxy-1H-indole-5-carboxylic acid [(S)-2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-7-methoxy-1H-indole-5-carboxylic acid [(R)-2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4-Chloro-7-(1-hydroxy-1-methyl-ethyl)-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

4,7-Difluoro-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide; and

4-Fluoro-7-methoxy-1H-indole-5-carboxylic acid [2-(2-methyl-pyrimidin-5-yl)-2-morpholin-4-yl-ethyl]-amide;

or a salt of such a compound.

12. The compound of formula (I Ar ) according to claim 7 , wherein A and B represent N:

or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition containing, as active principle, the compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

14. A method for the treatment of a disease selected from spinal cord injury, stroke, epilepsy, amyotrophic lateral sclerosis, pain, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, lung emphysema, glomerulonephritis, irritable bowel syndrome, psoriasis, atopic dermatitis, Crohn's disease, ulcerative colitis, diabetes mellitus, osteoporosis, and ischemic heart disease, comprising administering to a subject a pharmaceutically active amount of the compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof.

15. A method for the treatment of a disease selected from spinal cord injury, stroke, epilepsy, amyotrophic lateral sclerosis, pain, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, lung emphysema, glomerulonephritis, irritable bowel syndrome, psoriasis, atopic dermatitis, Crohn's disease, ulcerative colitis, diabetes mellitus, osteoporosis, and ischemic heart disease, comprising administering to a subject a pharmaceutically active amount of a compound according to claim 11 , or a pharmaceutically acceptable salt thereof.

16. The compound of formula (I Ar ) according to claim 8 , wherein

R 6 represents chloro;

or a salt of such a compound.

17. The compound of formula (I Ar ) according to claim 8 , wherein

R 6 represents methyl;

or a salt of such a compound.

18. The compound of formula (I Ar ) according to claim 12 , wherein

R 6 represents chloro;

or a salt of such a compound.

19. The compound of formula (I Ar ) according to claim 12 , wherein

R 6 represents methyl;

or a salt of such a compound.

Assignments (3)
CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE ADDRESS PREVIOUSLY RECORDED AT REEL: 042464 FRAME: 0407. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Jun 28, 2017
From: ACTELION PHARMACEUTICALS LTD
To: IDORSIA PHARMACEUTICALS LTD
Reel/Frame 043017/0022 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 13, 2017
From: ACTELION PHARMACEUTICALS LTD
To: IDORSIA PHARMACEUTICALS LTD
Reel/Frame 042464/0407 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 19, 2015
From: HILPERT, KURT; HUBLER, FRANCIS; KIMMERLIN, THIERRY; RENNEBERG, DORTE; STAMM, SIMON
To: ACTELION PHARMACEUTICALS LTD.
Reel/Frame 035864/0694 →