US 2020/0392155 A1Published application

Pyrazine carbamates and their use as glun2b receptor modulators

AssigneeJanssen Pharmaceutica NV

InventorChristine GELIN

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Abstract

Pyridine carbamates, pharmaceutical compositions containing pyridine carbamates, and uses of the pyridine carbamates and pharmaceutical compositions for modulating GluN2B receptors and for treating diseases, disorders, and medical conditions mediated by GluN2B receptor activity.

Claims32

Dependent claims

A compound of Formula (I):

or a pharmaceutically acceptable salt, solvate, isotopic variant, or N-oxide thereof, wherein:
n is 0 or 1;
R2 is H or C1-C6alkyl;
R3 is H or C1-C6alkyl;
R5 is aryl which is optionally substituted with one or two substituents each of which is independently halogen, C1-C6haloalkyl, or O—C1-C6haloalkyl;
and
R6a and R6b are, each independent from the other, H or C1-C6alkyl which is optionally substituted with (═O) and a 4 to 6 membered heterocycloalkyl, —NHCH3, or —N(CH3)2;
or R6a and R6b together with the carbon atom to which they are attached form (i) a C3-C6cycloalkyl ring or (ii) a 4 to 6 membered heterocycloalkyl ring which is optionally substituted with C1-C6alkyl.

5 more elements

A compound, or a pharmaceutically acceptable salt, solvate, isotopic variant, or N-oxide thereof, wherein the compound is

3-[[6-[3-(Difluoromethyl)-4-fluoro-phenyl]pyrazin-2-yl]methyl]oxazolidin-2-one;
3-[[6-[3-(Difluoromethoxy)-4-fluoro-phenyl]pyrazin-2-yl]methyl]oxazolidin-2-one;
5-[[6-[3-(Difluoromethyl)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-7-oxa-5-azaspiro[2.4]heptan-6-one;
3-[[6-[3-(Difluoromethyl)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-5,5-dimethyl-oxazolidin-2-one;
(5R)-3-[[6-[3-(Difluoromethyl)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-5-methyl-oxazolidin-2-one;
(5S)-3-[[6-[3-(Difluoromethyl)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-5-methyl-oxazolidin-2-one;
(4R)-3-[[6-[3-(Difluoromethyl)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-4-methyl-oxazolidin-2-one;
(4S)-3-[[6-[3-(Difluoromethyl)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-4-methyl-oxazolidin-2-one;
3-[[6-[3-(Difluoromethyl)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-1,3-oxazinan-2-one;
5-[[6-[3-(Difluoromethyl)-4-fluoro-phenyl]-3-methyl-pyrazin-2-yl]methyl]-7-oxa-5-azaspiro[2.4]heptan-6-one;
(4R)-3-[[6-[3-(Difluoromethyl)-4-fluoro-phenyl]-3-methyl-pyrazin-2-yl]methyl]-4-methyl-oxazolidin-2-one;
(4S)-3-[[6-[3-(Difluoromethyl)-4-fluoro-phenyl]-3-methyl-pyrazin-2-yl]methyl]-4-methyl-oxazolidin-2-one;
(5R)-3-[[6-[3-(Difluoromethyl)-4-fluoro-phenyl]-3-methyl-pyrazin-2-yl]methyl]-5-methyl-oxazolidin-2-one;
(5S)-3-[[6-[3-(Difluoromethyl)-4-fluoro-phenyl]-3-methyl-pyrazin-2-yl]methyl]-5-methyl-oxazolidin-2-one;
3-[[6-[3-(Difluoromethyl)-4-fluoro-phenyl]-3-methyl-pyrazin-2-yl]methyl]-1,3-oxazinan-2-one;
5-[[6-[3-(Difluoromethoxy)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-7-oxa-5-azaspiro[2.4]heptan-6-one;
3-[[6-[3-(Difluoromethoxy)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-5,5-dimethyl-oxazolidin-2-one;
(4R)-3-[[6-[3-(Difluoromethoxy)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-4-methyl-oxazolidin-2-one;
(4S)-3-[[6-[3-(Difluoromethoxy)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-4-methyl-oxazolidin-2-one;
(5R)-3-[[6-[3-(Difluoromethoxy)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-5-methyl-oxazolidin-2-one;
(5S)-3-[[6-[3-(Difluoromethoxy)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-5-methyl-oxazolidin-2-one;
3-[[6-[3-(Difluoromethoxy)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-1,3-oxazinan-2-one;
5-[[6-[3-(Difluoromethoxy)-4-fluoro-phenyl]-3-methyl-pyrazin-2-yl]methyl]-7-oxa-5-azaspiro[2.4]heptan-6-one;
(4R)-3-[[6-[3-(Difluoromethoxy)-4-fluoro-phenyl]-3-methyl-pyrazin-2-yl]methyl]-4-methyl-oxazolidin-2-one;
(4S)-3-[[6-[3-(Difluoromethoxy)-4-fluoro-phenyl]-3-methyl-pyrazin-2-yl]methyl]-4-methyl-oxazolidin-2-one;
(5R)-3-[[6-[3-(Difluoromethoxy)-4-fluoro-phenyl]-3-methyl-pyrazin-2-yl]methyl]-5-methyl-oxazolidin-2-one;
(5S)-3-[[6-[3-(Difluoromethoxy)-4-fluoro-phenyl]-3-methyl-pyrazin-2-yl]methyl]-5-methyl-oxazolidin-2-one;
3-[[6-[3-(Difluoromethoxy)-4-fluoro-phenyl]-3-methyl-pyrazin-2-yl]methyl]-1,3-oxazinan-2-one;
5-[[6-[4-Chloro-3-(difluoromethoxy)phenyl]pyrazin-2-yl]methyl]-7-oxa-5-azaspiro[2.4]heptan-6-one;
3-[[6-[4-Chloro-3-(difluoromethoxy)phenyl]pyrazin-2-yl]methyl]-5,5-dimethyl-oxazolidin-2-one;
(5R)-3-[[6-[4-Chloro-3-(difluoromethoxy)phenyl]pyrazin-2-yl]methyl]-5-methyl-oxazolidin-2-one;
(5S)-3-[[6-[4-Chloro-3-(difluoromethoxy)phenyl]pyrazin-2-yl]methyl]-5-methyl-oxazolidin-2-one;
(4R)-3-[[6-[4-Chloro-3-(difluoromethoxy)phenyl]pyrazin-2-yl]methyl]-4-methyl-oxazolidin-2-one;
(4S)-3-[[6-[4-Chloro-3-(difluoromethoxy)phenyl]pyrazin-2-yl]methyl]-4-methyl-oxazolidin-2-one;
3-[[6-[4-Chloro-3-(difluoromethoxy)phenyl]pyrazin-2-yl]methyl]-1,3-oxazinan-2-one;
5-[[6-[4-Chloro-3-(difluoromethoxy)phenyl]-3-methyl-pyrazin-2-yl]methyl]-7-oxa-5-azaspiro[2.4]heptan-6-one;
3-[[6-[4-Chloro-3-(difluoromethoxy)phenyl]-3-methyl-pyrazin-2-yl]methyl]-1,3-oxazinan-2-one;
5-[[6-[3-(1,1-Difluoroethyl)phenyl]pyrazin-2-yl]methyl]-7-oxa-5-azaspiro[2.4]heptan-6-one;
3-[[6-[3-(1,1-Difluoroethyl)phenyl]pyrazin-2-yl]methyl]-5,5-dimethyl-oxazolidin-2-one;
(5R)-3-[[6-[3-(1,1-Difluoroethyl)phenyl]pyrazin-2-yl]methyl]-5-methyl-oxazolidin-2-one;
(5S)-3-[[6-[3-(1,1-Difluoroethyl)phenyl]pyrazin-2-yl]methyl]-5-methyl-oxazolidin-2-one;
3-[[6-[3-(1,1-Difluoroethyl)phenyl]pyrazin-2-yl]methyl]-1,3-oxazinan-2-one;
5-[[6-[3-(1,1-Difluoroethyl)phenyl]-3-methyl-pyrazin-2-yl]methyl]-7-oxa-5-azaspiro[2.4]heptan-6-one;
3-[[6-[3-(1,1-Difluoroethyl)phenyl]-3-methyl-pyrazin-2-yl]methyl]-5,5-dimethyl-oxazolidin-2-one;
3-[[6-[3-(1,1-Difluoroethyl)phenyl]-3-methyl-pyrazin-2-yl]methyl]-1,3-oxazinan-2-one;
(4R)-3-[[6-[3-(1,1-Difluoroethyl)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-4-methyl-oxazolidin-2-one;
(4S)-3-[[6-[3-(1,1-Difluoroethyl)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-4-methyl-oxazolidin-2-one;
6-[[6-[3-(1,1-Difluoroethyl)phenyl]pyrazin-2-yl]methyl]-8-oxa-6-azaspiro[2.5]octan-7-one;
6-[[6-[3-(Difluoromethoxy)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-8-oxa-6-azaspiro[2.5]octan-7-one;
6-[[6-[4-Chloro-3-(difluoromethoxy)phenyl]pyrazin-2-yl]methyl]-8-oxa-6-azaspiro[2.5]octan-7-one;
6-[[6-[4-Chloro-3-(difluoromethoxy)phenyl]-3-methyl-pyrazin-2-yl]methyl]-8-oxa-6-azaspiro[2.5]octan-7-one;
6-[[6-[3-(Difluoromethyl)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-8-oxa-6-azaspiro[2.5]octan-7-one;
6-[[6-[3-(Difluoromethyl)-4-fluoro-phenyl]-3-methyl-pyrazin-2-yl]methyl]-8-oxa-6-azaspiro[2.5]octan-7-one;
6-[[6-[3-(Difluoromethoxy)-4-fluoro-phenyl]-3-methyl-pyrazin-2-yl]methyl]-8-oxa-6-azaspiro[2.5]octan-7-one;
(R/S)-3-[[6-[4-Chloro-3-(difluoromethoxy)phenyl]pyrazin-2-yl]methyl]-N,N-dimethyl-2-oxo-oxazolidine-5-carboxamide;
(R/S)-3-[[6-[4-Chloro-3-(difluoromethoxy)phenyl]pyrazin-2-yl]methyl]-N-methyl-2-oxo-oxazolidine-5-carboxamide;
5-(Azetidine-1-carbonyl)-3-[[6-[4-chloro-3-(difluoromethoxy)phenyl]pyrazin-2-yl]methyl]oxazolidin-2-one;
(R/S)-5-(Azetidine-1-carbonyl)-3-[[6-[3-(difluoromethyl)-4-fluoro-phenyl]pyrazin-2-yl]methyl]oxazolidin-2-one;
(R/S)-3-[[6-[3-(Difluoromethyl)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-N-methyl-2-oxo-oxazolidine-5-carboxamide;
(R/S)-3-[[6-[3-(Difluoromethoxy)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-N-methyl-2-oxo-oxazolidine-5-carboxamide;
(R/S)-5-(Azetidine-1-carbonyl)-3-[[6-[3-(difluoromethoxy)-4-fluoro-phenyl]pyrazin-2-yl]methyl]oxazolidin-2-one;
(R/S)-3-[[6-[3-(1,1-Difluoroethyl)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-N,N-dimethyl-2-oxo-oxazolidine-5-carboxamide;
(R/S)-3-[[6-[3-(1,1-Difluoroethyl)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-N-methyl-2-oxo-oxazolidine-5-carboxamide;
(R/S)-5-(Azetidine-1-carbonyl)-3-[[6-[3-(1,1-difluoroethyl)-4-fluoro-phenyl]pyrazin-2-yl]methyl]oxazolidin-2-one;
(R/S)-3-[[6-[3-(Difluoromethyl)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-N,N-dimethyl-2-oxo-oxazolidine-5-carboxamide;
(R/S)-3-[[6-[3-(Difluoromethoxy)-4-fluoro-phenyl]pyrazin-2-yl]methyl]-N,N-dimethyl-2-oxo-oxazolidine-5-carboxamide;
6-[[6-[4-Chloro-3-(difluoromethoxy)phenyl]pyrazin-2-yl]methyl]-8-oxa-2,6-diazaspiro[3.4]octan-7-one;
or
6-[[6-[4-Chloro-3-(difluoromethoxy)phenyl]pyrazin-2-yl]methyl]-2-methyl-8-oxa-2,6-diazaspiro[3.4]octan-7-one.

66 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/899,817Filed 12 Jun 2020
Priority: 14 Jun 2019
Published: 17 Dec 2020
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 codes

A61P 25/00
Drugs for disorders of the nervous system
C07D 498/10
In which the condensed system contains two hetero rings: spiro-condensed systems
A61P 25/08
Drugs for disorders of the nervous system: antiepileptics; Anticonvulsants
A61P 25/18
Drugs for disorders of the nervous system: antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia

Family

Application62/861,642Us provisional application · filed 14 Jun 2019
US 11,459,336 B2Related patent
US 2020/0392155 A1This patent

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

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Abstract

Facts

Application

16/899,817Filed 12 Jun 2020

Priority

14 Jun 2019

Published

17 Dec 2020

Term ends

Not estimatedThe source records don’t support an estimate.

Classification9 codes

A61P 25/00
Drugs for disorders of the nervous system
C07D 498/10
In which the condensed system contains two hetero rings: spiro-condensed systems
A61P 25/08
Drugs for disorders of the nervous system: antiepileptics; Anticonvulsants
A61P 25/18
Drugs for disorders of the nervous system: antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia