US 10,329,295 B2Granted

Pyrrolotriazine inhibitors of IRAK4 activity

AssigneeMerck Sharp & Dohme Corp.

InventorsJongwon Lim, Michael D. Altman, Jason D. Brubaker, Craig R. Gibeau

Life of this patent

Estimating the term…

Abstract

The present invention relates to pyrrolotriazine inhibitors of IRAK4 of formula (I) and provides compositions comprising such inhibitors, as well as methods therewith for treating IRAK4-mediated or -associated conditions or diseases.

Claims8

Dependent claims

A compound according to Formula I:

wherein:
Ring A is aryl or heterocyclyl;
n is 0, 1, 2, 3 or 4;
R1 is independently selected from:
(C1-C4)alkyl, (C3-C6)cycloalkyl, heterocyclyl, CF3, CHF2, CN, halo, said alkyl, cycloalkyl and heterocyclyl optionally substituted with halo, OH, CH3, and OCH3;
R2 is H and R3 is independently selected from:
(C1-C6)alkyl, (C3-C8)cycloalkyl, and heterocyclyl each optionally substituted with one or more halo, OH, N(Rb)2, or morpholinyl, or R2 and R3 can be taken together with the nitrogen to which they are attached to form a heterocyclyl, said heterocyclyl optionally substituted with one or more substituents selected from Ra;
Ra is independently selected from (C1-C4)alkyl, (C3-C6)cycloalkyl, CF3, CHF2, OH, halo and NH2, said alkyl optionally substituted with (C3-C6)cycloalkyl and CF3;
and
Rb is independently selected from H and (C1-C4)alkyl;
or a pharmaceutically acceptable salt thereof.

8 more elements

A compound which is selected from:

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-hydroxycyclohexyl]amino}-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]-2-piperazin-1-ylpyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]-2-[(3R)-piperidin-3-ylamino]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(1,4-diazepan-1-yl)-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3R)-3-aminopiperidin-1-yl]-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(5,8-diazaspiro[2.6]non-5-yl)-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(azepan-3-ylamino)-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]-2-piperazin-1-ylpyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(4-cyanothiophen-3-yl)-2-(1,4-diazepan-1-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(4-cyanothiophen-3-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(4-bromothiophen-3-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(1,4-diazepan-1-yl)-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]-2-[(3R)-piperidin-3-ylamino]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]-2-{[(1R,2S)-2-hydroxycyclohexyl]amino}pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3R)-3-aminopiperidin-1-yl]-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(azepan-3-ylamino)-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(5,8-diazaspiro[2.6]non-5-yl)-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(2-cyanothiophen-3-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-cyanothiophen-3-yl)-2-(2,5-diazabicyclo[2.2.2]oct-2-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(4-bromothiophen-3-yl)-2-(1,4-diazepan-1-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(4-bromothiophen-3-yl)-2-(2,5-diazabicyclo[2.2.2]oct-2-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(3-chloro-1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-chloro-1-methyl-1H-pyrazol-4-yl)-2-(1,4-diazepan-1-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-[2-(trifluoromethyl)phenyl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(1,4-diazepan-1-yl)-N-[2-(trifluoromethyl)phenyl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(2,5-diazabicyclo[2.2.2]oct-2-yl)-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(2-chlorothiophen-3-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-chlorothiophen-3-yl)-2-(1,4-diazepan-1-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(2-bromophenyl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-bromophenyl)-2-(1,4-diazepan-1-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-cyano-1-methyl-1H-pyrazol-4-yl)-2-(1,4-diazepan-1-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(3-cyano-1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(4-cyanothiophen-3-yl)-2-(2,5-diazabicyclo[2.2.2]oct-2-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-bromothiophen-3-yl)-2-(1,4-diazepan-1-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(2-bromothiophen-3-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-chlorophenyl)-2-(1,4-diazepan-1-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(2-chlorophenyl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(1,4-diazepan-1-yl)-N-[4-(difluoromethyl)thiophen-3-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-[4-(difluoromethyl)thiophen-3-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-cyanothiophen-3-yl)-2-(1,4-diazepan-1-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-chloro-1-methyl-1H-pyrazol-4-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-chloro-1-methyl-1H-pyrazol-4-yl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-cyano-1-methyl-1H-pyrazol-4-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-cyano-1-methyl-1H-pyrazol-4-yl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-bromothiophen-3-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-bromothiophen-3-yl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(2-cyanophenyl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3R)-3-aminopiperidin-1-yl]-N-(2-cyanophenyl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-cyanophenyl)-2-[(3R)-piperidin-3-ylamino]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-chlorothiophen-3-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-chlorothiophen-3-yl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-chlorophenyl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-[2-(difluoromethyl)phenyl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(1,4-diazepan-1-yl)-N-[2-(difluoromethyl)phenyl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-cyanophenyl)-2-piperazin-1-ylpyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-cyanophenyl)-2-(1,4-diazepan-1-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3S)-azepan-3-ylamino]-N-(2-cyanophenyl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]-N-[2-(difluoromethyl)phenyl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(1R,4R)-2,5-diazabicyclo[2.2.2.2]oct-2-yl]-N-[2-(difluoromethyl)phenyl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-bromo-1-methyl-1H-pyrazol-4-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-bromo-1-methyl-1H-pyrazol-4-yl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-chlorophenyl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(3-bromo-1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-bromo-1-methyl-1H-pyrazol-4-yl)-2-(1,4-diazepan-1-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]-N-[2-(trifluoromethyl)phenyl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3S)-azepan-3-ylamino]-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-[1-methyl-5-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-cyanophenyl)-2-{[(1R,2S)-2-hydroxycyclohexyl]amino}pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3R)-azepan-3-ylamino]-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3R)-azepan-3-ylamino]-N-(2-cyanophenyl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-cyanophenyl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-cyanophenyl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-cyanophenyl)-2-(5,8-diazaspiro[2.6]non-5-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-bromophenyl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]-N-[2-(trifluoromethyl)phenyl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(3-chloro-1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]-N-[4-(difluoromethyl)thiophen-3-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]-N-[4-(difluoromethyl)thiophen-3-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(3,8-diazabicyclo[3.2.1]oct-3-yl)-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(3,8-diazabicyclo[3.2.1]oct-3-yl)-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-bromophenyl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(1,4-diazepan-1-yl)-N-[2-(trifluoromethyl)thiophen-3-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]-N-[2-(trifluoromethyl)thiophen-3-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]-N-[2-(trifluoromethyl)thiophen-3-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-[2-(trifluoromethyl)thiophen-3-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(3-bromo-1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3R)-azepan-3-ylamino]-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3S)-azepan-3-ylamino]-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-[4-(difluoromethyl)thiophen-3-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(2-bromothiophen-3-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-[2-(trifluoromethyl)thiophen-3-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(3,8-diazabicyclo[3.2.1]oct-8-yl)-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(2-chlorothiophen-3-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(3-cyano-1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(3,6-diazabicyclo[3.2.1]oct-3-yl)-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(1S,5S)-3,6-diazabicyclo[3.2.1]oct-3-yl]-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(1R,5R)-3,6-diazabicyclo[3.2.1]oct-3-yl]-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(3,6-diazabicyclo[3.2.1]oct-3-yl)-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(1S,5S)-3,6-diazabicyclo[3.2.1]oct-3-yl]-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(1R,5R)-3,6-diazabicyclo[3.2.1]oct-3-yl]-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(4-chlorothiophen-3-yl)-2-(1,4-diazepan-1-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(2-bromophenyl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(4-chlorothiophen-3-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(4-chlorothiophen-3-yl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(4-chlorothiophen-3-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-cyano-1-methyl-1H-pyrazol-4-yl)-2-(3,8-diazabicyclo[3.2.1]oct-3-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-cyano-1-methyl-1H-pyrazol-4-yl)-2-(3,8-diazabicyclo[3.2.1]oct-8-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-cyano-1-methyl-1H-pyrazol-4-yl)-2-(3,6-diazabicyclo[3.2.1]oct-3-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-cyano-1-methyl-1H-pyrazol-4-yl)-2-[(1S,5S)-3,6-diazabicyclo[3.2.1]oct-3-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-cyano-1-methyl-1H-pyrazol-4-yl)-2-[(1R,5R)-3,6-diazabicyclo[3.2.1]oct-3-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(3,6-diazabicyclo[3.2.1]oct-6-yl)-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(1S,5R)-3,6-diazabicyclo[3.2.1]oct-6-yl]-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(1R,5S)-3,6-diazabicyclo[3.2.1]oct-6-yl]-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(3,6-diazabicyclo[3.2.1]oct-6-yl)-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(1S,5R)-3,6-diazabicyclo[3.2.1]oct-6-yl]-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(1R,5S)-3,6-diazabicyclo[3.2.1]oct-6-yl]-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-(3,8-diazabicyclo[3.2.1]oct-8-yl)-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-cyano-1-methyl-1H-pyrazol-4-yl)-2-{[(1R,2S)-2-hydroxycyclohexyl]amino}pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3S)-3-aminopiperidin-1-yl]-N-(3-cyano-1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-cyano-1-methyl-1H-pyrazol-4-yl)-2-[(3R)-piperidin-3-ylamino]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3R)-3-aminopiperidin-1-yl]-N-(3-cyano-1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(4-chlorothiophen-3-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1S,2R)-2-amino-5,5-difluorocyclohexyl]amino}-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1S,2R)-2-amino-4,4-difluorocyclohexyl]amino}-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1S,2R)-2-amino-4,4-difluorocyclohexyl]amino}-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1S,2R)-2-amino-5,5-difluorocyclohexyl]amino}-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1S,2R)-2-amino-5,5-difluorocyclohexyl]amino}-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1S,2R)-2-amino-4,4-difluorocyclohexyl]amino}-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-cyano-1-methyl-1H-pyrazol-4-yl)-2-(3,6-diazabicyclo[3.2.1]oct-6-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-cyano-1-methyl-1H-pyrazol-4-yl)-2-(3,6-diazabicyclo[3.2.1]oct-6-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(3-cyano-1-methyl-1H-pyrazol-4-yl)-2-(3,6-diazabicyclo[3.2.1]oct-6-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(2-cyanophenyl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-[2-(trifluoromethyl)phenyl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(2-chlorophenyl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1S,2R)-2-amino-4,4-difluorocyclohexyl]amino}-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1S,2R)-2-amino-5,5-difluorocyclohexyl]amino}-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3R)-3-aminopiperidin-1-yl]-N-(2-cyanothiophen-3-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(4-cyanothiophen-3-yl)-2-{[(1R,2S)-2-hydroxycyclohexyl]amino}pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3S)-3-aminopiperidin-1-yl]-N-(4-cyanothiophen-3-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3R)-3-aminopiperidin-1-yl]-N-(4-cyanothiophen-3-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(4-cyanothiophen-3-yl)-2-[(3R)-piperidin-3-ylamino]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-cyanothiophen-3-yl)-2-[(3R)-piperidin-3-ylamino]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-(2-cyanothiophen-3-yl)-2-{[(1R,2S)-2-hydroxycyclohexyl]amino}pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3S,5R)-3-amino-5-fluoropiperidin-1-yl]-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3R,5R)-3-amino-5-fluoropiperidin-1-yl]-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3S,5S)-3-amino-5-fluoropiperidin-1-yl]-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3S,5R)-3-amino-5-fluoropiperidin-1-yl]-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3S)-3-aminopiperidin-1-yl]-N-(2-cyanothiophen-3-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(4-cyanothiophen-3-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(3S,5R)-5-fluoropiperidin-3-yl]amino}-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]-2-{[(3S,5R)-5-fluoropiperidin-3-yl]amino}pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3R,5R)-3-amino-5-fluoropiperidin-1-yl]-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3S,5S)-3-amino-5-fluoropiperidin-1-yl]-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(2-cyanothiophen-3-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]-2-{[(3R,5S)-5-fluoropiperidin-3-yl]amino}pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(3R,5S)-5-fluoropiperidin-3-yl]amino}-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(3S,5S)-5-fluoropiperidin-3-yl]amino}-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(3R,5R)-5-fluoropiperidin-3-yl]amino}-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(3R,5S)-3-amino-5-fluoropiperidin-1-yl]-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]-2-{[(3S,5S)-5-fluoropiperidin-3-yl]amino}pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]-2-{[(3R,5R)-5-fluoropiperidin-3-yl]amino}pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(1-ethyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-[1-(2-methoxyethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(1-methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
and
2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrrolo[2,1-f][1,2,4]triazine-7-carboxamide;
or a pharmaceutically acceptable salt thereof.

170 more elements

Dependencies are inferred from the claim text.

Facts

Application: 15/557,203Filed 7 Mar 2016 · us provisional application
Priority: 12 Mar 2015
Published: US 2018/0051030 A122 Feb 2018
Granted: 25 Jun 2019
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 codes

C07D 487/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61K 31/519
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: ortho- or peri-condensed with heterocyclic rings
A61K 31/53
Having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins: having six-membered rings with three nitrogens as the only ring hetero…
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…

Family

Application62/132,202Us provisional application · filed 12 Mar 2015
US 2018/0051030 A1Pre-grant publication · published 22 Feb 2018
US 10,329,295 B2This patent

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

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Abstract

Facts

Application

15/557,203Filed 7 Mar 2016 · us provisional application

Priority

12 Mar 2015

Published

US 2018/0051030 A122 Feb 2018

Granted

25 Jun 2019

Term ends

Not estimatedThe source records don’t support an estimate.

Classification9 codes

C07D 487/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61K 31/519
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: ortho- or peri-condensed with heterocyclic rings
A61K 31/53
Having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins: having six-membered rings with three nitrogens as the only ring hetero…
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…