US 2014/0005188 A1Published application

Pyrido[3,4-b]pyrazine derivatives as syk inhibitors

AssigneeGlaxo Group Limited

InventorsFrancis Louis Atkinson, Stephen John Atkinson, Michael David Barker, Clement Douault, Neil Stuart Garton, John Liddle, Vipulkumar Kantibhai Patel, Alexander G. Preston, Tracy Jane Shipley, David Matthew Wilson, Robert J. Watson

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Abstract

A compound of formula (I): or a salt thereof; which is an inhibitor of spleen tyrosine kinase (Syk) and therefore potentially of use in treating diseases resulting from inappropriate activation of mast cells, macrophages, and B-cells and related inflammatory responses and tissue damage, for instance inflammatory disease and/or allergic disorders, and in cancer therapy, specifically heme malignancies, and autoimmune conditions.

Claims14

Dependent claims

A compound of formula (I):

wherein:
X is O, CH2 or NH;
R1 is a 5- or 6-membered heterocyclyl or —(CH2)nR5;
wherein the heterocyclyl is optionally substituted by one or two groups each independently selected from fluoro, methyl, ethyl and trifluoroethyl;
R2 is a 5- or 6-membered heteroaryl, heterocyclyl or phenyl, or a 9- or 10-membered fused heteroaryl;
wherein the heteroaryl, heterocyclyl, phenyl or fused heteroaryl is optionally substituted by one or two groups each independently selected from C1-6alkyl, OH, C1-6alkoxy, —NR3R4, C1-6-fluoroalkyl, benzyl, C3-6cycloalkyl, oxo (═O), OC1-6-fluoroalkyl and halogen;
R3 and R4 are each independently selected from hydrogen and methyl, or R3 and R4 together with the nitrogen to which they are attached form a 5- or 6-membered heterocyclyl;
R5 is —NH2, —CF3, —C(O)NH2 or OH;
and
n is an integer selected from 0, 1, 2 and 3;
or
a pharmaceutically acceptable salt thereof.

9 more elements

A compound which is selected from the group consisting of:

7-[1-(Phenylmethyl)-1H-pyrazol-4-yl]-N-[(3S)-3-piperidinylmethyl]pyrido[3,4-b]pyrazin-5-amine;
7-(1-Cyclopentyl-1H-pyrazol-4-yl)-N-[(3S)-3-piperidinylmethyl]pyrido[3,4-b]pyrazin-5-amine;
N-{[(3S)-3-fluoro-3-piperidinyl]methyl}-7-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-amine;
7-[3,4-bis(Methyloxy)phenyl]-N-{[(3S)-3-fluoro-3-piperidinyl]methyl}pyrido[3,4-b]pyrazin-5-amine hydrochloride;
N-{[(3S)-3-Fluoro-3-piperidinyl]methyl}-7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-amine hydrochloride;
5-{[(3S)-3-piperidinylmethyl]oxy}-7-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazine hydrochloride;
7-(1,5-Dimethyl-1H-pyrazol-4-yl)-5-{[(3S)-3-piperidinylmethyl]oxy}pyrido[3,4-b]pyrazine, hydrochloride;
N,N-Dimethyl-5-(5-{[(3S)-3-piperidinylmethyl]oxy}pyrido[3,4-b]pyrazin-7-yl)-2-pyridinamine hydrochloride;
7-(1-Methyl-1H-pyrazol-4-yl)-5-{[(3S)-3-piperidinylmethyl]oxy}pyrido[3,4-b]pyrazine hydrochloride;
7-(1,5-Dimethyl-1H-pyrazol-4-yl)-5{[(2S)-2-morpholinylmethyl]oxy}pyrido[3,4-b]pyrazine, hydrochloride;
7-(1-Methyl-1H-pyrazol-4-yl)-N-[(2S)-2-morpholinylmethyl]pyrido[3,4-b]pyrazin-5-amine, hydrochloride;
N-{[(2S)-1-methyl-2-piperazinyl]methyl}-7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-amine hydrochloride;
5-{[(4,4-Difluoro-3-piperidinyl)methyl]oxy}-7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazine;
7-(1-Methyl-1H-pyrazol-4-yl)-5-[2-(3-piperidinyl)ethyl]pyrido[3,4-b]pyrazine hydrochloride;
N-{7-[6-(Dimethylamino)-3-pyridinyl]pyrido[3,4-b]pyrazin-5-yl}-1,4-butanediamine hydrochloride;
7-[6-(dimethylamino)-3-pyridinyl]-N-[(2)-2-morpholinylmethyl]pyrido[3,4-b]pyrazin-5-amine, hydrochloride (Isomer 1);
7-[6-(dimethylamino)-3-pyridinyl]-N-[2-morpholinylmethyl]pyrido[3,4-b]pyrazin-5-amine, hydrochloride (Isomer 2);
N-[(4,4-difluoro-3-piperidinyl methyl]-7-[6-(dimethylamino)-3-pyridinyl]pyrido[3,4-b]pyrazin-5-amine (Isomer 2);
N-[(4,4-difluoro-3-piperidinyl methyl]-7-[6-(dimethylamino)-3-pyridinyl]pyrido[3,4-b]pyrazin-5-amine (Isomer 1);
N-((5,5-difluoropiperidin-3-yl)methyl)-7-(6-(dimethylamino)pyridin-3-yl)pyrido[3,4-b]pyrazin-5-amine;
4-(5-{[(3S)-3-piperidinyl methyl]amino}pyrido[3,4-b]pyrazin-7-yl)-2-piperazinone, hydrochloride;
7-(1-piperazinyl)-N-[(3S)-3-piperidinylmethyl]pyrido[3,4-b]pyrazin-5-amine, hydrochloride;
N,N-dimethyl-5-(5-{[(3R)-3-piperidinylmethyl]oxy}pyrido[3,4-b]pyrazin-7-yl)-2-pyridinamine;
7-[6-(dimethylamino)-3-pyridinyl]-N-(2,2,2-trifluoroethyl)pyrido[3,4-b]pyrazin-5-amine;
4-({7-[6-(dimethylamino)-3-pyridinyl]pyrido[3,4-b]pyrazin-5-yl}amino)-1-butanol;
N3-{7-[6-(dimethylamino)-3-pyridinyl]pyrido[3,4-b]pyrazin-5-yl}-β-alaninamide;
7-[6-(dimethylamino)-3-pyridinyl]-N-[(3S)-3-piperidinylmethyl]pyrido[3,4-b]pyrazin-5-amine;
N,N-di methyl-5-{5-[2-(3-piperidinyl ethyl]pyrido[3,4-b]pyrazin-7-yl}-2-pyridinamine;
7-(1-methyl-1H-pyrazol-4-yl)-N-[(3S)-3-piperidinylmethyl]pyrido[3,4-b]pyrazin-5-amine;
N-[(5,5-difluoro-3-piperidinyl)methyl]-7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-amine;
7-[6-(dimethylamino)-3-pyridinyl]-N-[(3R)-3-piperidinylmethyl]pyrido[3,4-b]pyrazin-5-amine;
N-[(3S)-3-piperidinylmethyl]-7-[6-(1-pyrrolidinyl)-3-pyridinyl]pyrido[3,4-b]pyrazin-5-amine;
7-[6-(1-piperazinyl)-3-pyridinyl]-N-[(3S)-3-piperidinyl methyl]pyrido[3,4-b]pyrazin-5-amine;
7-(6-amino-3-pyridinyl)-N-[(3S)-3-piperidinylmethyl]pyrido[3,4-b]pyrazin-5-amine;
7-(2-amino-5-pyrimidinyl)-N-[(3S)-3-piperidinylmethyl]pyrido[3,4-b]pyrazin-5-amine;
5-(5-{[(3S)-3-piperidinyl methyl]amino}pyrido[3,4-b]pyrazin-7-yl)-2(1H)-pyridinone;
N-[(3S)-3-piperidinylmethyl]-7-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrido[3,4-b]pyrazin-5-amine;
7-(5-methyl-2-thienyl)-N-[(3S)-3-piperidinylmethyl]pyrido[3,4-b]pyrazin-5-amine;
7-(5-methyl-2-furanyl)-N-[(3S)-3-piperidinylmethyl]pyrido[3,4-b]pyrazin-5-amine;
N-[(3S)-3-piperidinylmethyl]-7-(1H-pyrazol-3-yl)pyrido[3,4-b]pyrazin-5-amine;
N-[(3S)-3-piperidinylmethyl]-7-(1H-pyrazol-3-yl)pyrido[3,4-b]pyrazin-5-amineN-[7-4-methylphenyl)pyrido[3,4-b]pyrazin-5-yl]-1,4-butanediamine;
7-(4-methylphenyl)-N-(morpholin-2-ylmethyl)pyrido[3,4-b]pyrazin-5-amine hydrochloride, single unknown enantiomer;
7-(4-methylphenyl)-N-(morpholin-2-ylmethyl)pyrido[3,4-b]pyrazin-5-amine hydrochloride, single unknown enantiomer;
7-(4-methoxyphenyl)-N-[(3S)-piperidin-3-ylmethyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
(3S)-3-({[7-(4-methylphenyl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine hydrochloride;
7-(2,3-dihydro-1-benzofuran-5-yl)-N-[(3S)-piperidin-3-ylmethyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(1,3-benzothiazol-5-yl)-N-[(3S)-piperidin-3-ylmethyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(1H-indol-5-yl)-N-[(3S)-piperidin-3-ylmethyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(2,3-dihydro-1,4-benzodioxin-6-yl)-N-[(3S)-piperidin-3-ylmethyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-[6-(morpholin-4-yl)pyridin-3-yl]-N-[(3S)-piperidin-3-ylmethyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
N-[(3S)-piperidin-3-ylmethyl]-7-[6-propan-2-yloxyl)pyridin-3-yl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
(3S)-3-({[7-(4-methoxyphenyl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine hydrochloride;
(3S)-3-({[7-(1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine hydrochloride;
(3S)-3-({[7-(1-benzofuran-3-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine hydrochloride;
(3S)-3-{[(7-{1H-pyrrolo[3,2-c]pyridin-3-yl}pyrido[3,4-b]pyrazin-5-yl)oxy]methyl}piperidine hydrochloride;
(3S)-3-{[(7-{1H-pyrrolo[2,3-b]pyridin-3-yl}pyrido[3,4-b]pyrazin-5-yl)oxy]methyl}piperidine hydrochloride;
(2R)-2-({[7-(1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)morpholine hydrochloride;
(2R)-2-({[7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)morpholine hydrochloride;
N,N-dimethyl-5-{5-[(2R)-morpholin-2-ylmethoxy]pyrido[3,4-b]pyrazin-7-yl}pyridin-2-amine hydrochloride;
N-(morpholin-2-ylmethyl)-7-(1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-amine hydrochloride, single unknown enantiomer;
(3S)-3-{[(7-{4-methyl-2H,3H,4H-pyrido[3,2-b][1,4]oxazin-7-yl}pyrido[3,4-b]pyrazin-5-yl)oxy]methyl}piperidine hydrochloride;
(3S)-3-[({7-[1-(propan-2-yl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-yl}oxy)methyl]piperidine hydrochloride;
(3S)-3-[({7-[1-(propan-2-yl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-yl}oxy)methyl]piperidine;
N,N-dimethyl-5-{5-[(3S)-piperidin-3-ylmethoxy]pyrido[3,4-b]pyrazin-7-yl}pyrimidin-2-amine hydrochloride;
(3S)-3-({[7-(2,3-dihydro-1,4-benzodioxin-6-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine hydrochloride;
(3S)-3-({[7-(4-chlorophenyl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine;
(3S)-[({7-[4-(propan-2-yloxy)phenyl]pyrido[3,4-b]pyrazin-5-yl}oxy)methyl]piperidine;
(3S)-3-({[7-(1-ethyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine hydrochloride;
N,N-dimethyl-5-[5-({[(2S)-1-methylpiperazin-2-yl]methyl}amino)pyrido[3,4-b]pyrazin-7-yl]pyridin-2-amine hydrochloride;
4-(5-{5-[(3S)-piperidin-3-ylmethoxy]pyrido[3,4-b]pyrazin-7-yl}pyridin-2-yl)morpholine
(3S)-3-({[7-(3-methylphenyl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine dihydrochloride;
N-(morpholin-2-ylmethyl) 7-[6-(morpholin-4-yl)pyridin-3-yl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
single unknown enantiomer;
N-{[(2S)-1-methylpiperazin-2-yl]methyl}-7-(1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-amine hydrochloride;
N-{[(2S)-1-methylpiperazin-2-yl]methyl}-7-[6-(morpholin-4-yl)pyridin-3-yl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
(3S)-3-({[7-(1,3-dimethyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine;
(3S)-3-({[7-(1,3-dimethyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine hydrochloride;
7-(1-ethyl-1H-pyrazol-4-yl)-N-[(2R)-morpholin-2-ylmethyl]pyrido[3,4-b]pyrazin-5-amine;
N-[(2R)-morpholin-2-ylmethyl]-7-[1-(propan-2-yl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-amine;
(3S)-3-({[7-(2-chloro-4-methylphenyl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine hydrochloride;
(3S)-3-({[7-(3-chloropheny)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine hydrochloride;
N-{[(2S)-1-methylpiperazin-2-yl]methyl}-7-[1-(propan-2-yl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
(3S)-[({7-[4-(trifluoromethyl phenyl]pyrido[3,4-b]pyrazin-5-yl}oxy)methyl]piperidine hydrochloride;
(3S)-[({7-[4-(trifluoromethyl)phenyl]pyrido[3,4-b]pyrazin-5-yl}oxy)methyl]piperidine;
(3S)-3-({[7-(2-fluoro-4-methylphenyl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine;
N,N-dimethyl-5-(5-{[(2S)-1-methylpiperazin-2-yl]methoxy}pyrido[3,4-b]pyrazin-7-yl)pyridin-2-amine;
(2S)-1-methyl-2-({[7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperazine
7-(1,3-dimethyl-1H-pyrazol-4-yl)-N-[(2S)-morpholin-2-ylmethyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
N,N-dimethyl-5-[5-({[(2R)-1-methylpiperazin-2-yl]methyl}amino)pyrido[3,4-b]pyrazin-7-yl]pyridin-2-amine hydrochloride;
7-(1,5-dimethyl-1H-pyrazol-4-yl)-N-[(2S)-morpholin-2-ylmethyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
(2S)-2-({[7-(4-methylphenyl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)morpholine hydrochloride;
7-(1-methyl-1H-pyrazol-5-yl)-N-[(2S)-morpholin-2-ylmethyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(1,3-dimethyl-1H-pyrazol-5-yl)-N-[(2S)-morpholin-2-ylmethyl]pyrido[3,4-b]pyrazin-5-amine;
7-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(2S)-morpholin-2-ylmethyl]pyrido[3,4-b]pyrazin-5-amine;
N-[(2S)-morpholin-2-ylmethyl]-7-[6-(morpholin-4-yl)pyridin-3-yl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(1-ethyl-1H-pyrazol-4-yl)-N-[(2S)-morpholin-2-ylmethyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
N-[(2S)-morpholin-2-ylmethyl]-7-[1-(propan-2-yl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-amine;
(2S)-2-({[7-(1,5-dimethyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)-1-methylpiperazine
(2S)-2-({[7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)morpholine hydrochloride;
N-[(2S)-morpholin-2-ylmethyl]-7-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
N-[(2S)-morpholin-2-ylmethyl]-7-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-amine;
N-[(2S)-morpholin-2-ylmethyl]-7-(1-propyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-amine;
N-[(2S)-morpholin-2-ylmethyl]-7-(1-propyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(4-tert-butylphenyl)-N-[(2S)-morpholin-2-ylmethyl]pyrido[3,4-b]pyrazin-5-amine;
(2S)-1-ethyl-2-({[7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperazine hydrochloride;
5-{5-[(3-fluoropiperidin-3-yl)methoxy]pyrido[3,4-b]pyrazin-7-yl}-N,N-dimethylpyridin-2-amine;
5-{5-[(3-fluoropiperidin-3-ylmethoxy]pyrido[3,4-b]pyrazin-7-yl}-N,N-dimethylpyridin-2-amine, single unknown enantiomer;
5-{5-[(3-fluoropiperidin-3-yl)methoxy]pyrido[3,4-b]pyrazin-7-yl}-N,N-dimethylpyridin-2-amine, single unknown enantiomer;
5-(5-{[(2S)-1-ethylpiperazin-2-yl]methoxy}pyrido[3,4-b]pyrazin-7-yl)-N,N-dimethylpyridin-2-amine hydrochloride;
(3S)-3-{[(7-{4H,5H,6H-pyrrolo[1,2-b]pyrazol-3-yl}pyrido[3,4-b]pyrazin-5-yl)oxy]methyl}piperidine;
(3R)-3-({[7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine;
N,N-dimethyl-5-(5-{[(2S)-1-(2,2,2-trifluoroethyl)piperazin-2-yl]-methoxy}pyrido[3,4-b]pyrazin-7-yl)pyridin-2-amine;
(2S)-2-({[7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)-1-(2,2,2-trifluoroethyl)piperazine
(6S)-2,2-dimethyl-6-({[7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)morpholine
N-[(4,4-difluoropiperidin-3-yl)methyl]-7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-amine;
3-fluoro-3-({[7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine, single unknown enantiomer;
3-fluoro-3-({[7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine, single unknown enantiomer;
5-[5-({[(3R)-3-fluoropiperidin-3-yl]methyl}amino)pyrido[3,4-b]pyrazin-7-yl]-N,N-dimethylpyridin-2-amine hydrochloride;
N-{[(3S)-3-fluoropiperidin-3-yl]methyl}-7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-amine hydrochloride;
N-[(4,4-difluoropiperidin-3-yl)methyl]-7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-amine, single unknown enantiomer;
N-[(4,4-difluoropiperidin-3-yl)methyl]-7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-amine, single unknown enantiomer;
5-[5-({[(3S)-3-fluoropiperidin-3-yl]-methyl}amino)pyrido[3,4-b]pyrazin-7-yl]-N,N-dimethylpyridin-2-amine hydrochloride;
(2S,3S)-2-methyl-3-({[7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine;
7-(1-methyl-1H-pyrazol-4-yl)-N-[(2R)-morpholin-2-ylmethyl]pyrido[3,4-b]pyrazin-5-amine;
3,3-difluoro-5-({[7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine hydrochloride;
N-[(3-fluoropiperidin-3-yl)methyl]-7-(4-methylphenyl)pyrido[3,4-b]pyrazin-5-amine;
N-[(3-fluoropiperidin-3-yl)methyl]-7-(6-methoxypyridin-3-yl)pyrido[3,4-b]pyrazin-5-amine;
N-[(3-fluoropiperidin-3-yl)methyl]-7-(5-methoxypyridin-3-yl)pyrido[3,4-b]pyrazin-5-amine;
N-[(3-fluoropiperidin-3-yl)methyl]-7-(6-methylpyridin-3-yl)pyrido[3,4-b]pyrazin-5-amine;
N-[(3-fluoropiperidin-3-yl)methyl]-7-(4-methoxyphenyl)pyrido[3,4-b]pyrazin-5-amine;
N-[(4,4-difluoropiperidin-3-yl)methyl]-7-(4-methyl phenyl)pyrido[3,4-b]pyrazin-5-amine;
N-[(4,4-difluoropiperidin-3-yl)methyl]-7-(4-methoxyphenyl)pyrido[3,4-b]pyrazin-5-amine;
5-(5-{[(3-fluoropiperidin-3-yl)methyl]amino}pyrido[3,4-b]pyrazin-7-yl)-N,N-dimethylpyrimidin-2-amine;
N-(4-methylphenyl)-5-[(3S)-piperidin-3-ylmethoxy]pyrido[3,4-b]pyrazin-7-amine hydrochloride;
7-(1-cyclopentyl-1H-pyrazol-4-yl)-N-[(3-fluoropiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(1-cyclopentyl-1H-pyrazol-4-yl)-N-[(3-fluoropiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine;
N-[(3-fluoropiperidin-3-yl)methyl]-7-[1-(propan-2-yl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
N-[(3-fluoropiperidin-3-yl)methyl]-7-[1-(pentan-3-yl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(1-benzyl-1H-pyrazol-4-yl)-N-[(3-fluoropiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(1-ethyl-1H-pyrazol-4-yl)-N-[(3-fluoropiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(1,5-dimethyl-1H-pyrazol-4-yl)-N-[(3-fluoropiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
N-[(3-fluoropieridin-3-yl)methyl]-7-[1-(2-methylpropyl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
N-[(3-fluoropieridin-3-yl)methyl]-7-(1-propyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-N-[(3S)-piperidin-3-ylmethyl]pyrido[3,4-b]pyrazin-5-amine;
7-(1,5-dimethyl-1H-pyrazol-4-yl)-N-[(3S)-piperidin-3-ylmethyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
(3S)-[({7-[(4-methylphenyl methyl]pyrido[3,4-b]pyrazin-5-yl}oxy)methyl]piperidine hydrochloride;
7-(1,3-dimethyl-1H-pyrazol-4-yl)-N-[(3S)-piperidin-3-ylmethyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
N-[(3S)-piperidin-3-ylmethyl]-7-(1-propyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(1,3-dimethyl-1H-pyrazol-4-yl)-N-[(3-fluoropiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(1-ethyl-1H-pyrazol-4-yl)-N-[(3S)-piperidin-3-ylmethyl]pyrido[3,4-b]pyrazin-5-amine;
7-[1-(pentan-3-yl)-1H-pyrazol-4-yl]-N-[(3S)-piperidin-3-ylmethyl]pyrido[3,4-b]pyrazin-5-amine;
N-[(3S)-piperidin-3-ylmethyl]-7-[1-(propan-2-yl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-amine;
N-[(3S)-piperidin-3-ylmethyl]-7-[1-(propan-2-yl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(dimethyl-1,2-oxazol-4-yl)-N-[(3-fluoropiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
N-[(3-fluoropiperidin-3-yl)methyl]-7-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
3-(2-{7-[1-(propan-2-yl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-yl}ethyl)piperidine;
7-[5-methyl-1-(propan-2-yl)-1H-pyrazol-4-yl]-N-[(3S)-piperidin-3-ylmethyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
(+/−)(3S,5R)-3-fluoro-5-({[7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine;
(+/−)(3R,5R)-3-fluoro-5-({[7-(1-methyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine;
N-[(3-fluoropiperidin-3-yl)methyl]-7-[3-(trifluoromethoxy)phenyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
N-[(3-fluoropiperidin-3-yl)methyl]-7-[4-(trifluoromethoxy phenyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
N-[(3-fluoropiperidin-3-yl)methyl]-7-(1,3-oxazol-5-yl)pyrido[3,4-b]pyrazin-5-amine;
7-(2,4-difluorophenyl)-N-[(3-fluoropiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine;
7-(4-fluorophenyl)-N-[(3-fluoropiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine;
7-(3,4-difluorophenyl)-N-[(3-fluoropiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine;
3-fluoro-3-(2-{7-[1-(propan-2-yl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-yl}ethyl)piperidine;
N-[(3-fluoropiperidin-3-yl)methyl]-7-(2-methyl-1,3-benzothiazol-5-yl)pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(1-methyl-1H-pyrazol-4-yl)-N-[(3R)-piperidin-3-ylmethyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(1,3-dimethyl-1H-pyrazol-4-yl)-N-{[(3S)-3-fluoropiperidin-3-yl]methyl}pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(6-ethoxypyridin-3-yl)-N-[(3-fluoropiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(1,3-benzothiazol-6-yl)-N-[(3-fluoropiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
N-[(3-fluoropiperidin-3-yl)methyl]-7-(2-methyl-1,3-benzoxazol-5-yl)pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(1-methyl-1H-pyrazol-4-yl)-N-[(6-methylpiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
single unknown enantiomer;
7-(2,3-dihydro-1,4-benzodioxin-6-yl)-N-[(3-fluoropiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
N-[(3-fluoropiperidin-3-yl)methyl]-7-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]pyrido[3,4-b]pyrazin-5-amine;
N-[(3-fluoropiperidin-3-yl)methyl]-7-(pyridin-4-yl)pyrido[3,4-b]pyrazin-5-amine hydrochloride;
3-({[7-(1-ethyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)-3-fluoropiperidine hydrochloride;
7-(1,3-benzothiazol-5-yl)-N-[(3-fluoropiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(1-methyl-1H-pyrazol-4-yl)-N-[(6-methylpiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride, single unknown enantiomer;
N-[(3-fluoropiperidin-3-yl)methyl]-7-(2-methyl-1,3-benzoxazol-6-yl)pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(1-methyl-1H-pyrazol-4-yl)-N-[(6-methylpiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride, single unknown enantiomer;
7-(1-methyl-1H-pyrazol-4-yl)-N-[(6-methylpiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride, single unknown enantiomer;
5-{5-[(3-fluoropiperidin-3-yl)methoxy]pyrido[3,4-b]pyrazin-7-yl}-N,N-dimethylpyrimidin-2-amine hydrochloride;
N-[(3-fluoropiperidin-3-yl)methyl]-7-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-amine, single unknown enantiomer;
N-[(3-fluoropiperidin-3-yl)methyl]-7-[1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-amine hydrochloride, single unknown enantiomer;
3-fluoro-3-[({7-[1-(propan-2-yl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-yl}oxy)methyl]piperidine hydrochloride;
7-(1-ethyl-1H-pyrazol-4-yl)-N-[(3R)-piperidin-3-ylmethyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(1-ethyl-1H-pyrazol-4-yl)-N-[(3R)-piperidin-3-ylmethyl]pyrido[3,4-b]pyrazin-5-amine;
N-[(3R)-piperidin-3-ylmethyl]-7-[1-(propan-2-yl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-amine;
7-(1-tert-butyl-1H-pyrazol-4-yl)-N-[(3-fluoropiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(3,4-dimethoxyphenyl)-N-[(3-fluoropiperidin-3-yl)methyl]pyrido[3,4-b]pyrazin-5-amine;
(3R)-3-({[7-(1-ethyl-1H-pyrazol-4-yl)pyrido[3,4-b]pyrazin-5-yl]oxy}methyl)piperidine;
N-[(3-fluoropiperidin-3-yl)methyl]-7-[5-methyl-1-(propan-2-yl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-amine;
N-[(3-fluoropiperidin-3-yl)methyl]-7-[1-(methoxymethyl)-1H-pyrazol-4-yl]pyrido[3,4-b]pyrazin-5-amine;
7-(1-tert-butyl-1H-pyrazol-4-yl)-N-{[(3S)-3-fluoropiperidin-3-yl]methyl}pyrido[3,4-b]pyrazin-5-amine;
7-(1-tert-butyl-1H-pyrazol-4-yl)-N-{[(3S)-3-fluoropiperidin-3-yl]methyl}pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(3,4-dimethoxyphenyl)-N-[(3R)-piperidin-3-ylmethyl]pyrido[3,4-b]pyrazin-5-amine;
7-(3,4-dimethoxyphenyl)-N-[(3R)-piperidin-3-ylmethyl]pyrido[3,4-b]pyrazin-5-amine hydrochloride;
7-(5,6-dimethoxypyridin-3-yl)-N-{[(3S)-3-fluoropiperidin-3-yl]methyl}pyrido[3,4-b]pyrazin-5-amine;
7-(2,2-difluoro-2H-1,3-benzodioxol-5-yl)-N-{[(3S)-3-fluoropiperidin-3-yl]methyl}pyrido[3,4-b]pyrazin-5-amine;
and salts thereof.

199 more elements

Dependencies are inferred from the claim text.