US 2025/0019382 A1Published application

Novel inhibitors of cyclin-dependent kinases

AssigneeOrigenis GmbH

InventorsRoland Koestler, Julie Kondrotas, Jean Tassel, Michael Thormann, Nadine Traube

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Abstract

The present invention relates to novel compounds of formula (I): These compounds are inhibitors of CDK2 and/or CDK9 and are useful in the treatment of a variety of diseases including hyperproliferative diseases, virally induced infectious diseases, and cardiovascular diseases.

Claims29

Dependent claims

A compound of formula (I):

wherein
R1 is an alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, aryl, heteroaryl, aralkyl or heteroaralkyl group;
all of which groups may optionally be substituted;
R2 is selected from the following groups:
wherein
X is a carbon atom of an optionally substituted alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, aryl, heteroaryl, aralkyl or heteroaralkyl group;
X1 is a carbon atom of an optionally substituted alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkylcycloalkyl or heteroalkylcycloalkyl group;
Y is a halogen atom, CN, OH, NH2, N3;
or a carbon atom of an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl or aralkyl group;
or a carbon or nitrogen, atom of an optionally substituted heterocycloalkyl or heteroaryl group;
or a carbon, nitrogen oxygen or sulfur atom of an optionally substituted heteroalkyl, heteroalkylcycloalkyl, or heteroaralkyl group;
Y1 is an oxygen atom, a sulfur atom, NH;
or a carbon atom of an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl or alkylcycloalkyl group;
or a carbon or nitrogen atom of an optionally substituted heteroalkyl or heteroalkylcycloalkyl group;
Z and Z2 are a carbon atom of an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl or aralkyl group;
or a carbon or nitrogen atom of an optionally substituted heterocycloalkyl or heteroaryl group;
or a carbon, nitrogen, oxygen or sulfur atom of an optionally substituted heteroalkyl, heteroalkylcycloalkyl or heteroaralkyl group;
and
Z1 is a carbon atom of an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl or alkylcycloalkyl group;
or a carbon or nitrogen atom of an optionally substituted heteroalkyl or heteroalkylcycloalkyl group;
or
X and Z, or X and Z1, or X and Z2, or X1 and Z, or X1 and Z1 together are part of a ring of a cycloalkyl or heterocycloalkyl group, or X and Z, or X1 and Z1 together are part of a ring of an aryl or heteroaryl group;
wherein X is a carbon atom, X1 is a carbon atom, Z is a carbon, nitrogen, oxygen or sulfur atom, Z1 is a carbon or nitrogen atom and Z2 is a carbon, nitrogen, oxygen or sulfur atom;
R3 is a hydrogen atom, a halogen atom, a CN group or an alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, aryl, heteroaryl, aralkyl or heteroaralkyl group;
all of which groups may optionally be substituted;
and
R4 is a hydrogen atom, a halogen atom, a CN group or an alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, aryl, heteroaryl, aralkyl or heteroaralkyl group;
all of which groups may optionally be substituted;
or
R3 and R4 together form a fused cycloalkyl, heterocycloalkyl, aryl or heteroaryl group;
all of which groups may optionally be substituted;
or a salt thereof.

29 more elements

A compound which is selected from the following compounds;

or a salt thereof:
2-(2,6-difluorophenyl)-N-(3-ethoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-dichlorophenyl)-N-(3-ethoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-dichlorophenyl)-N-(3-ethoxy-4-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(3-ethoxy-4-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine
2-(2-chloro-6-fluorophenyl)-N-(3,3-dimethyl-2,3-dihydrobenzofuran-6-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2-chloro-6-fluorophenyl)-N-(3-ethoxy-4-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2-chloro-6-fluorophenyl)-N-(3-ethoxy-4-(1-methylpiperidin-4-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-dichlorophenyl)-N-(3-ethoxy-4-(1-methylpiperidin-4-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-dichlorophenyl)-N-(3,3-dimethyl-2,3-dihydrobenzofuran-6-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(3-ethoxy-4-(1-methylpiperidin-4-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(3,3-dimethyl-2,3-dihydrobenzofuran-6-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
4-((2-(2-chloro-6-fluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)-N-(2,2,2-trifluoroethyl)benzamide;
N-(tert-butyl)-4-((2-(2-chloro-6-fluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)benzamide;
4-((2-(2-chloro-6-fluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)-N-ethylbenzamide;
4-((2-(2-chloro-6-fluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)-N-(tetrahydro-2H-pyran-4-yl)benzamide;
4-((2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)-N-(2,2,2-trifluoroethyl)benzamide;
N-(tert-butyl)-4-((2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)benzamide;
4-((2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)-N-ethylbenzamide;
4-((2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)-N-(tetrahydro-2H-pyran-4-yl)benzamide;
N-(4-(1-cyclopropyl-1,2,3,6-tetrahydropyridin-4-yl)-3-ethoxyphenyl)-2-(2,6-dichlorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
N-(4-(1-cyclopropylpiperidin-4-yl)-3-ethoxyphenyl)-2-(2,6-dichlorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2-chloro-6-fluorophenyl)-N-(3-ethoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2-chloro-6-fluorophenyl)-N-(4-(1-cyclopropylpiperidin-4-yl)-3-ethoxyphenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2-chloro-6-fluorophenyl)-N-(4-(1-cyclopropyl-1,2,3,6-tetrahydropyridin-4-yl)-3-ethoxyphenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(4-((2-(2-chloro-6-fluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)phenyl)-2-methylpropanenitrile;
2-(4-((2-(2-chloro-6-fluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)-1H-pyrazol-1-yl)-2-methylpropanenitrile;
2-(2,6-difluorophenyl)-N-(4-morpholinophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
1-(4-(4-((2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)phenyl)piperazin-1-yl)ethan-1-one;
2-(2,6-difluorophenyl)-N-(3-fluoro-4-morpholinophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(3-methoxy-4-morpholinophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
5-((2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)-2-morpholinobenzonitrile;
2-(2,6-difluorophenyl)-N-(4-(4-morpholinopiperidin-1-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(3-isopropoxy-4-morpholinophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(4-((2S,6R)-2,6-dimethylmorpholino)-3-ethoxyphenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(3-isopropoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2-fluorophenyl)-N-(4-morpholinophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2-fluorophenyl)-N-(4-(4-methylpiperazin-1-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
1-(4-(4-((2-(2-fluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)phenyl)piperazin-1-yl)ethan-1-one;
N-(3-fluoro-4-morpholinophenyl)-2-(2-fluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-2-(2-fluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2-fluorophenyl)-N-(3-methoxy-4-morpholinophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
5-((2-(2-fluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)-2-morpholinobenzonitrile;
2-(2-fluorophenyl)-N-(4-(4-morpholinopiperidin-1-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2-fluorophenyl)-N-(3-isopropoxy-4-morpholinophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2-fluorophenyl)-N-(4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2-fluorophenyl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2-fluorophenyl)-N-(3-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(3-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
N-(2-(1H-pyrazol-1-yl)benzyl)-8-bromo-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(3,4-dimethoxyphenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(1-(1′-methyl-[1,4′-bipiperidin]-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(1-((1r,4r)-4-morpholinocyclohexyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
N-(2-(1H-pyrazol-1-yl)benzyl)-7-cyclopropyl-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-((1r,4r)-4-morpholinocyclohexyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2-chloro-6-fluorophenyl)-N-(1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
7-cyclopropyl-2-(2,6-difluorophenyl)-N-(1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
N-(5-chloro-1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-pyrazol-4-yl)-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
N-(3-chloro-1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-pyrazol-4-yl)-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2-chloro-6-fluorophenyl)-N-((1r,4r)-4-morpholinocyclohexyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-8-methyl-N-(1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-pyrazol-4-yl)-8,9-dihydro-7H-cyclopenta[3,4]pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-7-methyl-N-(1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
N-(1-(1-(cyclopropylmethyl)piperidin-4-yl)-1H-pyrazol-4-yl)-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(1-(1-(2-fluoroethyl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
methyl-4-(4-((2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)-1H-pyrazol-1-yl)piperidine-1-carboxylate;
N-(1-(1-cyclopropylpiperidin-4-yl)-1H-pyrazol-4-yl)-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(1-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
N-(1-(1-(2,2-difluoroethyl)piperidin-4-yl)-1H-pyrazol-4-yl)-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
N-(1-(1-(but-3-en-1-yl)piperidin-4-yl)-1H-pyrazol-4-yl)-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-4-((1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-pyrazol-4-yl)amino)pyrazolo[1,5-a][1,3,5]triazine-8-carbonitrile;
8-chloro-2-(2,6-difluorophenyl)-N-((1r,4r)-4-morpholinocyclohexyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-8-phenyl-N-(1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-((1r,4r)-4-morpholinocyclohexyl)-8-phenylpyrazolo[1,5-a][1,3,5]triazin-4-amine;
8-chloro-2-(2,6-difluorophenyl)-N-(1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-4-(((1r,4r)-4-morpholinocyclohexyl)amino)pyrazolo[1,5-a][1,3,5]triazine-8-carbonitrile;
8-bromo-2-(2,6-difluorophenyl)-N-(1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
8-bromo-2-(2,6-difluorophenyl)-N-((1r,4r)-4-morpholinocyclohexyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
8-chloro-2-(2,6-difluorophenyl)-N-(1-(1′-methyl-[1,4′-bipiperidin]-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
N-(4-(4-(tert-butyl)piperazin-1-yl)phenyl)-8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
(4-((8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)phenyl)(morpholino)methanone;
8-chloro-N-(1-(1-cyclopropylpiperidin-4-yl)-1H-pyrazol-4-yl)-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
8-chloro-N-(1-(1-(cyclopropylmethyl)piperidin-4-yl)-1H-pyrazol-4-yl)-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
8-chloro-2-(2-chloro-6-fluorophenyl)-N-(1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
8-chloro-2-(2,6-dichlorophenyl)-N-(1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
8-chloro-2-(2,6-difluorophenyl)-N-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
8-chloro-2-(2,6-difluorophenyl)-N-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
8-chloro-2-(2,6-difluorophenyl)-N-(1-methyl-1H-pyrazol-3-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
8-chloro-2-(2,6-difluorophenyl)-N-(1-methyl-1H-imidazol-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-((4-((8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)pentyl)(ethyl)amino)ethan-1-ol;
(1r,4r)-N1-(8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)cyclohexane-1,4-diamine;
(1r,4r)-N1-(8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)-N4,N4-dimethylcyclohexane-1,4-diamine;
8-chloro-2-(2,6-difluorophenyl)-N-((1r,4r)-4-(piperidin-1-yl)cyclohexyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-N-((1r,4r)-4-morpholinocyclohexyl)-8-(trifluoromethyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
(1s,4s)-N1-(8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)cyclohexane-1,4-diamine;
8-chloro-2-(2,6-difluorophenyl)-N-((1s,4s)-4-(piperidin-1-yl)cyclohexyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
(1s,4s)-N1-(8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)-N4,N4-dimethylcyclohexane-1,4-diamine;
2-(2,6-difluorophenyl)-N-(1-methyl-1H-pyrazol-4-yl)-8-(trifluoromethyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
(1R,3R)-N1-(8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)cyclopentane-1,3-diamine;
N1-(8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)cyclopentane-1,3-diamine;
(1r,4r)-N1-(2-(2,6-difluorophenyl)-8-(trifluoromethyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)cyclohexane-1,4-diamine;
(1R,3R)-N1-(8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)-N3,N3-dimethylcyclopentane-1,3-diamine;
(1r,4r)-N1-(2-(2,6-difluorophenyl)-8-(trifluoromethyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)-N4,N4-dimethylcyclohexane-1,4-diamine;
(1r,4r)-N1-(8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)-N4-(2-methoxyethyl)cyclohexane-1,4-diamine;
(1S,3R)-N1-(8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)cyclopentane-1,3-diamine;
(1r,4r)-N1-(8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)-N4-(2-fluoroethyl)cyclohexane-1,4-diamine;
2-(((1r,4r)-4-((8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)cyclohexyl)amino)ethan-1-ol;
(1r,4r)-N1-(8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)-N4-(3-fluoropropyl)cyclohexane-1,4-diamine;
(1r,3r)-N1-(8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)cyclobutane-1,3-diamine;
(1r,3r)-N1-(8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)-N3,N3-dimethylcyclobutane-1,3-diamine;
(1r,4r)-N1-(8-chloro-2-(2,4,6-trifluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)-N4,N4-dimethylcyclohexane-1,4-diamine;
(1r,4r)-N1-(8-chloro-2-(2,6-difluoro-4-methylphenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)-N4,N4-dimethylcyclohexane-1,4-diamine;
2-(((1r,4r)-4-((8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)amino)cyclohexyl)(methyl)amino)ethan-1-ol;
3-({4-[8-Chloro-2-(2,6-difluoro-phenyl)-pyrazolo[1,5-a][1,3,5]triazin-4-ylamino]-cyclohexyl}-methyl-amino)-propan-1-ol;
(1r,4r)-N1-(8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)-N4-(3-fluoropropyl)-N4-methylcyclohexane-1,4-diamine;
8-chloro-2-(2,6-difluorophenyl)-N-((1r,4r)-4-(pyrrolidin-1-yl)cyclohexyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-8-ethynyl-N-((1r,4r)-4-morpholinocyclohexyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
2-(2,6-difluorophenyl)-8-iodo-N-((1r,4r)-4-morpholinocyclohexyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
8-chloro-2-(2,6-difluorophenyl)-N-(1-methylpiperidin-4-yl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
N-(8-chloro-2-(2,6-difluorophenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)quinuclidin-4-amine;
8-chloro-2-(2,6-difluorophenyl)-N-((1s,4s)-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
8-chloro-2-(2,6-difluorophenyl)-N-((1r,4r)-4-(4-methylpiperazin-1-yl)cyclohexyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
8-chloro-2-(2,6-difluorophenyl)-N-((4,6-dimethylpyridin-3-yl)methyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine;
and
8-chloro-2-(2,6-difluorophenyl)-N-(pyridin-3-ylmethyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine.

129 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/711,682Filed 21 Nov 2022
Priority: EP 21210011.923 Nov 2021
Published: 16 Jan 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification7 codes

C07D 487/04
In which the condensed system contains two hetero rings: ortho-condensed systems
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…
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents
A61P 35/00
Antineoplastic agents

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Abstract

A compound of formula (I):

wherein
R1 is an alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, aryl, heteroaryl, aralkyl or heteroaralkyl group;
all of which groups may optionally be substituted;
R2 is selected from the following groups:
wherein
X is a carbon atom of an optionally substituted alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, aryl, heteroaryl, aralkyl or heteroaralkyl group;
X1 is a carbon atom of an optionally substituted alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkylcycloalkyl or heteroalkylcycloalkyl group;
Y is a halogen atom, CN, OH, NH2, N3;
or a carbon atom of an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl or aralkyl group;
or a carbon or nitrogen, atom of an optionally substituted heterocycloalkyl or heteroaryl group;
or a carbon, nitrogen oxygen or sulfur atom of an optionally substituted heteroalkyl, heteroalkylcycloalkyl, or heteroaralkyl group;
Y1 is an oxygen atom, a sulfur atom, NH;
or a carbon atom of an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl or alkylcycloalkyl group;
or a carbon or nitrogen atom of an optionally substituted heteroalkyl or heteroalkylcycloalkyl group;
Z and Z2 are a carbon atom of an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl or aralkyl group;
or a carbon or nitrogen atom of an optionally substituted heterocycloalkyl or heteroaryl group;
or a carbon, nitrogen, oxygen or sulfur atom of an optionally substituted heteroalkyl, heteroalkylcycloalkyl or heteroaralkyl group;
and
Z1 is a carbon atom of an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl or alkylcycloalkyl group;
or a carbon or nitrogen atom of an optionally substituted heteroalkyl or heteroalkylcycloalkyl group;
or
X and Z, or X and Z1, or X and Z2, or X1 and Z, or X1 and Z1 together are part of a ring of a cycloalkyl or heterocycloalkyl group, or X and Z, or X1 and Z1 together are part of a ring of an aryl or heteroaryl group;
wherein X is a carbon atom, X1 is a carbon atom, Z is a carbon, nitrogen, oxygen or sulfur atom, Z1 is a carbon or nitrogen atom and Z2 is a carbon, nitrogen, oxygen or sulfur atom;
R3 is a hydrogen atom, a halogen atom, a CN group or an alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, aryl, heteroaryl, aralkyl or heteroaralkyl group;
all of which groups may optionally be substituted;
and
R4 is a hydrogen atom, a halogen atom, a CN group or an alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, aryl, heteroaryl, aralkyl or heteroaralkyl group;
all of which groups may optionally be substituted;
or
R3 and R4 together form a fused cycloalkyl, heterocycloalkyl, aryl or heteroaryl group;
all of which groups may optionally be substituted;
or a salt thereof.

29 more elements

Facts

Application

18/711,682Filed 21 Nov 2022

Priority

EP 21210011.923 Nov 2021

Published

16 Jan 2025

Term ends

Not estimatedThe source records don’t support an estimate.

Classification7 codes

C07D 487/04
In which the condensed system contains two hetero rings: ortho-condensed systems
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…
A61P 29/00
Non-central analgesic, antipyretic or antiinflammatory agents
A61P 35/00
Antineoplastic agents