IP Library Granted Patent US 9,969,749
Granted Patent B2
US 9,969,749 · App. 15/515,383 · Granted May 15, 2018

Inhibitors of IRAK4 activity

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Quick Facts
Patent No.
US 9,969,749
App. No.
15/515,383
Granted
May 15, 2018
Kind
B2
Abstract

The present invention relates to 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.

Claims (198)

1. A compound according to Formula I:

wherein:

X is NH or O;

b is 0 or 1;

n is 0, 1, 2, 3 or 4;

R 1 and R 2 are independently H and (C 1 -C 4 )alkyl, or R 1 and R 2 can be taken together with the nitrogen to which they are attached to form a heterocycle optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N, O and S, said alkyl and heterocycle are optionally substituted with one or more substituents selected from R a ;

R 3 is (C 1 -C 4 )alkyl wherein two adjacent alkyl groups can join together and form a bridged moiety of 3-6 carbon atoms;

R 4 is absent, halo or O b (C 1 -C 4 )alkyl;

R 5 is aryl or heteroaryl each optionally substituted with one or more substituents selected from R b ;

R 6 is absent, halo, or O(C 1 -C 4 )alkyl;

R a is independently selected from: halo, O b (C 1 -C 4 )alkyl, SO 2 (C 1 -C 4 )alkyl, C(O)C 1 -C 4 alkyl, said alkyl optionally substituted with halo or heterocyclyl; and

R b is independently selected from OH, halo, CHF 2 , CF 3 , COOH, SO 2 (C 1 -C 4 )alkyl, C═O(O)C 1 -C 4 alkyl, O b (C 1 -C 4 )alkyl, aryl, heterocyclyl, CN, C(O)N(R c ) 2 , N(R c ) 2 ; said R c and alkyl are optionally substituted with OH, O(C 1 -C 4 )alkyl and heterocyclyl; and

R c is independently H, SO 2 (C 1 -C 4 )alkyl, or C 1 -C 4 alkyl;

or a pharmaceutically acceptable salt or a stereoisomer thereof.

2. A compound according to claim 1 of Formula II:

wherein:

b is 0 or 1;

R 1 and R 2 are independently H and (C 1 -C 4 )alkyl, or R 1 and R 2 can be taken together with the nitrogen to which they are attached to form: morpholinyl, piperidinyl, azetidinyl and piperazinyl, said alkyl, morpholinyl, piperidinyl, azetidinyl and piperaziyle are optionally substituted with one or more substituents selected from R a ;

R 4 is absent or methyl;

R 5 is aryl or heteroaryl each optionally substituted with one or more substituents selected from R b ;

R 6 is absent or F;

R a is independently selected from: F, O b (C 1 -C 4 )alkyl, SO 2 (C 1 -C 4 )alkyl, C(O)C 1 -C 4 alkyl, said alkyl optionally substituted with F or morpholinyl;

R b is independently selected from OH, halo, CHF 2 , CF 3 , COOH, SO 2 (C 1 -C 4 )alkyl, C═O(O)C 1 -C 4 alkyl, O b (C 1 -C 4 )alkyl, aryl, heterocyclyl, CN, C(O)N(R c ) 2 , N(R c ) 2 ; said R c and alkyl are optionally substituted with OH, O(C 1 -C 4 )alkyl and heterocyclyl; and

R c is independently H, SO 2 (C 1 -C 4 )alkyl, or C 1 -C 4 alkyl;

or a pharmaceutically acceptable salt or a stereoisomer thereof.

3. A compound which is selected from:

trans-N,N-dimethyl-N′-[6(6-methylpyridazin-4-yl)quinazolin-4-yl]cyclohexane-1,4-diamine;

cis or trans-N,N-dimethyl-N′-(6-phenylquinazolin-4-yl)cyclohexane-1,4-diamine;

cis or trans-N,N-dimethyl-N′-[6-(pyridin-4-yl)quinazolin-4-yl]cyclohexane-1,4-diamine;

cis or trans-N,N-dimethyl-N′-[6-(pyridin-3-yl)quinazolin-4-yl]cyclohexane-1,4-diamine;

cis or trans-N,N-dimethyl-N′-(6-phenylquinazolin-4-yl)cyclohexane-1,4-diamine;

cis or trans-N,N-dimethyl-N′-[6-(pyridin-4-yl)quinazolin-4-yl]cyclohexane-1,4-diamine;

cis or trans-N,N-dimethyl-N′-[6-(pyridin-3-yl)quinazolin-4-yl]cyclohexane-1,4-diamine;

trans-N′-[6-(2-methoxypyridin-4-yl)quinazolin-4-yl]-N,N-dimethylcyclohexane-1,4-diamine;

trans-N,N-dimethyl-N′-[6-(1-methyl-1H-pyrazol-4-yl)quinazolin-4-yl]cyclohexane-1,4-diamine;

cis or trans-N,N-dimethyl-N′-[6-(1H-pyrazol-4-yl)quinazolin-4-yl]cyclohexane-1,4-diamine;

cis or trans-N′-[6-(6-aminopyridin-3-yl)quinazolin-4-yl]-N,N-dimethylcyclohexane-1,4-diamine;

trans-N,N-dimethyl-N′-[6-(1H-pyrazol-3-yl)quinazolin-4-yl]cyclohexane-1,4-diamine;

trans-N,N-dimethyl-N′-{6-[2-(methylamino)pyrimidin-5-yl]quinazolin-4-yl}cyclohexane-1,4-diamine;

trans-N′-{6-[1-(1-ethoxyethyl)-1H-pyrazol-4-yl]quinazolin-4-yl}-N,N-dimethylcyclohexane-1,4-diamine;

trans-N,N-dimethyl-N′-(6-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}quinazolin-4-yl)cyclohexane-1,4-diamine;

trans-N,N-dimethyl-N-′-{6-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]quinazolin-4-yl}cyclohexane-1,4-diamine;

trans-N,N-dimethyl-N′-{6-[1-(pyridin-2-ylmethyl)-1H-pyrazol-4-yl]quinazolin-4-yl}cyclohexane-1,4-diamine;

trans-N′-[6-(1-ethyl-1H-pyrazol-4-yl)quinazolin-4-yl]-N,N-dimethylcyclohexane-1,4-diamine;

trans-N,N-dimethyl-N′-{6-[1-(pyridin-4-ylmethyl)-1H-pyrazol-4-yl]quinazolin-4-yl}cyclohexane-1,4-diamine;

4-(4-{[trans-4-(dimethylamino)cyclohexyl]amino}quinazolin-6-yl)pyridine-3-carbonitrile;

trans-N,N-dimethyl-N′-[6-(3-methylpyridin-4-yl)quinazolin-4-yl]cyclohexane-1,4-diamine;

3-(4-{[trans-4-(dimethylamino)cyclohexyl]amino}quinazolin-6-yl)pyridine-4-carbonitrile;

trans-N,N-dimethyl-N′-{6-[5-(morpholin-4-yl)pyridin-3-yl]quinazolin-4-yl}cyclohexane-1,4-diamine;

trans-N′-[6-(3,5-dimethylisoxazol-4-yl)quinazolin-4-yl]-N,N-dimethylcyclohexane-1,4-diamine;

trans-N,N-dimethyl-N′-[6-(pyrimidin-5-yl)quinazolin-4-yl]cyclohexane-1,4-diamine;

trans-N,N-dimethyl-N′-[6-(5-methyl-3-phenylisoxazol-4-yl)quinazolin-4-yl]cyclohexane-1,4-diamine;

5-(4-{[trans-4-(dimethylamino)cyclohexyl]amino}quinazolin-6-yl)pyridine-2-carbonitrile;

5-(4-{[trans-4-(dimethylamino)cyclohexyl]amino}quinazolin-6-yl)pyridin-2-ol;

trans-N′-[6-(2-aminopyrimidin-5-yl)quinazolin-4-yl]-N,N-dimethylcyclohexane-1,4-diamine;

trans-N,N-dimethyl-N′-[6-(6-methylpyridin-3-yl)quinazolin-4-yl]cyclohexane-1,4-diamine;

methyl 5-(4-{[trans-4-(dimethylamino)cyclohexyl]amino}quinazolin-6-yl)pyridine-3-carboxylate;

trans-N′-[6-(isoxazol-4-yl)quinazolin-4-yl]-N,N-dimethylcyclohexane-1,4-diamine;

5-(4-{[trans-4-(dimethylamino)cyclohexyl]amino}quinazolin-6-yl)pyrimidin-2-ol;

trans-N′-[6-(3-fluoropyridin-4-yl)quinazolin-4-yl]-N,N-dimethylcyclohexane-1,4-diamine;

trans-N′-[6-(4-methoxypyridin-3-yl)quinazolin-4-yl]-N,N-dimethylcyclohexane-1,4-diamine;

trans-N,N-dimethyl-N′-{6-[4-(trifluoromethyl)pyridin-3-yl]quinazolin-4-yl}cyclohexane-1,4-diamine;

5-(4-{[trans-4-(dimethylamino)cyclohexyl]amino}quinazolin-6-yl)pyridine-3-carboxylic acid;

trans-N′-[6-(3-methoxypyridin-4-yl)quinazolin-4-yl]-N,N-dimethylcyclohexane-1,4-diamine;

3-(4-{[trans-4-(dimethylamino)cyclohexyl]amino}quinazolin-6-yl)pyridine-2-carbonitrile;

trans-N′-{6-[5-(2-methoxyethoxy)pyridin-3-yl]quinazolin-4-yl}-N,N-dimethylcyclohexane-1,4-diamine;

trans-N,N-dimethyl-N′-{6-[5-(methylsulfonyl)pyridin-3-yl]quinazolin-4-yl}cyclohexane-1,4-diamine;

trans-N′-{6-[2-(cyclopropylamino)pyrimidin-5-yl]quinazolin-4-yl}-N,N-dimethylcyclohexane-1,4-diamine;

2-{[5-(4-{[trans-4-(dimethylamino)cyclohexyl]amino}quinazolin-6-yl)pyrimidin-2-yl]amino}ethanol;

3-(4-{[trans-4-(dimethylamino)cyclohexyl]amino}quinazolin-6-yl)benzonitrile;

trans-N′-[6-(1H-indol-5-yl)quinazolin-4-yl]-N,N-dimethylcyclohexane-1,4-diamine;

N-[trans-4-(morpholin-4-yl)cyclohexyl]-6-(pyridin-3-yl)quinazolin-4-amine;

N-[trans-4-(morpholin-4-yl)cyclohexyl]-6-(pyrimidin-5-yl)quinazolin-4-amine;

N-[trans-4-(morpholin-4-yl)cyclohexyl]-6-(pyridin-4-yl)quinazolin-4-amine;

trans-N′-[6-(2,3-dihydro-1,4-benzodioxin-6-yl)quinazolin-4-yl]-N,N-dimethylcyclohexane-1,4-diamine;

trans-N,N-dimethyl-N′-[6-(pyridazin-4-yl)quinazolin-4-yl]cyclohexane-1,4-diamine;

trans-N′-[6-(5-methoxypyridin-3-yl)quinazolin-4-yl]-N,N-dimethylcyclohexane-1,4-diamine;

trans-N′-[6-(5-fluoro-6-methoxypyridin-3-yl)quinazolin-4-yl]-N,N-dimethylcyclohexane-1,4-diamine;

trans-N′-[6-(5-fluoropyridin-3-yl)quinazolin-4-yl]-N,N-dimethylcyclohexane-1,4-diamine;

5-(4-{[trans-4-(dimethylamino)cyclohexyl]amino}quinazolin-6-yl)pyridine-3-carbonitrile;

trans-N,N-dimethyl-N′-[6-(1H-pyrrolo[2,3-b]pyridin-5-yl)quinazolin-4-yl]cyclohexane-1,4-diamine;

N-tert-butyl-5-(4-{[trans-4-(dimethylamino)cyclohexyl]amino}quinazolin-6-yl)pyridine-3-carboxamide;

trans-N,N-dimethyl-N′-[6-(4-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)quinazolin-4-yl]cyclohexane-1,4-diamine;

trans-N,N-dimethyl-N′-[6-(1H-pyrazolo[3,4-b]pyridin-5-yl)quinazolin-4-yl]cyclohexane-1,4-diamine;

trans-N,N-dimethyl-N′-[6-(1H-pyrrolo[3,2-b]pyridin-6-yl)quinazolin-4-yl]cyclohexane-1,4-diamine;

trans-N,N-dimethyl-N′-[6-(3-methyl-3H-imidazo[4,5-b]pyridin-6-yl)quinazolin-4-yl]cyclohexane-1,4-diamine;

trans-N′-[6-(furo[3,2-b]pyridin-6-yl)quinazolin-4-yl]-N,N-dimethylcyclohexane-1,4-diamine;

trans-N′-[6-(3,5-difluorophenyl)quinazolin-4-yl]-N,N-dimethylcyclohexane-1,4-diamine;

3-(4-{[trans-4-(dimethylamino)cyclohexyl]amino}quinazolin-6-yl)-5-fluorophenol;

5-(4-{[trans-4-(dimethylamino)cyclohexyl]amino}quinazolin-6-yl)-2,3-difluorophenol;

5-(4-{[trans-4-(morpholin-4-yl)cyclohexyl]amino}quinazolin-6-yl)pyridin-3-ol;

3-fluoro-5-{4-[(trans-4-morpholin-4-ylcyclohexyl)amino]quinazolin-6-yl}phenol;

4-{4-[(trans-4-morpholin-4-ylcyclohexyl)amino]quinazolin-6-yl}pyridin-2-ol ;

6-(3,5-difluorophenyl)-N-(trans-4-morpholin-4-ylcyclohexyl)quinazolin-4-amine;

6-(5-methoxypyridin-3-yl)-N′-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

2,3-difluoro-5-{4-[(trans-4-morpholin-4-ylcyclohexyl)amino]quinazolin-6-yl}phenol;

6-(5-amino-6-methoxypyridin-3-yl)-N-(trans-4-morpholin-4-ylcyclohexyl)quinazolin-4-amine;

3-{4-[(trans-4-morpholin-4-ylcyclohexyl)amino]quinazolin-6-yl}phenol;

6-(5-aminopyridin-3-yl)-N-(trans-4-morpholin-4-ylcyclohexyl)quinazolin-4-amine;

6-(2-aminopyridin-4-yl)-N-(trans-4-morpholin-4-ylcyclohexyl)quinazolin-4-amine;

6-(1-methyl-1H-pyrazol-4-yl)-N-(trans-4-morpholin-4-ylcyclohexyl)quinazolin-4-amine;

5-methyl-N-(trans-4-morpholin-4-ylcyclohexyl)-6-pyrimidin-5-ylquinazolin-4-amine;

5-methyl-6-(1-methyl-1H-pyrazol-4-yl)-N-(trans-4-morpholin-4-ylcyclohexyl)quinazolin-4-amine;

5-methyl-N-(trans-4-morpholin-4-ylcyclohexyl)-6-pyridin-4-ylquinazolin-4-amine;

5-{5-methyl-4-[(trans-4-morpholin-4-ylcyclohexyl)amino]quinazolin-6-yl}pyridin-3-ol;

7-fluoro-N-(trans-4-morpholin-4-ylcyclohexyl)-6-(1H-pyrazol-4-yl)quinazolin-4-amine;

6-[5-(methylamino)pyridin-3-yl]-N-(trans-4-morpholin-4-ylcyclohexyl)quinazolin-4-amine;

N-(trans-4-morpholin-4-ylcyclohexyl)-6-(1H-pyrazol-4-yl)quinazolin-4-amine;

6-(3-aminophenyl)-N-(trans-4-morpholin-4-ylcyclohexyl)quinazolin-4-amine;

5-{7-fluoro-4-[(trans-4-morpholin-4-ylcyclohexyl)amino]quinazolin-6-yl}pyridin-3-ol;

6-(5-aminopyridin-3-yl)-7-fluoro-N-(trans-4-morpholin-4-ylcyclohexyl)quinazolin-4-amine;

7-fluoro-6-[5-(methylamino)pyridin-3-yl]-N-(trans-4-morpholin-4-ylcyclohexyl)quinazolin-4-amine;

7-fluoro-N-(trans-4-morpholin-4-ylcyclohexyl)-6-pyrimidin-5-ylquinazolin-4-amine;

6-(1H-indol-4-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

6-(2-methylpyrimidin-5-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

N-[cis-4-(morpholin-4-yl)cyclohexyl]-6-[2-(trifluoromethyl)pyrimidin-5-yl]quinazolin-4-amine;

N-[trans-4-(morpholin-4-yl)cyclohexyl]-6-(1H-pyrazol-3-yl)quinazolin-4-amine;

N-[5-(4-{[trans-4-(morpholin-4-yl)cyclohexyl]amino}quinazolin-6-yl)pyridin-3-yl]methanesulfonamide;

6-(5-methylpyridin-3-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

[5-(4-{[trans-4-(morpholin-4-yl)cyclohexyl]amino}quinazolin-6-yl)pyridin-3-yl]methanol;

2-[5-(4-{[trans-4-(morpholin-4-yl)cyclohexyl]amino}quinazolin-6-yl)pyridin-3-yl]propan-2-ol;

6-(isoxazol-4-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

6-(5-fluoropyridin-3-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

5-(4-{[trans-4-(morpholin-4-yl)cyclohexyl]amino}quinazolin-6-yl)pyridine-3-carbonitrile;

6-(5-chloropyridin-3-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

2-chloro-5-(4-{[trans-4-(morpholin-4-yl)cyclohexyl]amino}quinazolin-6-yl)pyridin-3-ol;

ethyl 1-methyl-3-(4-(((trans)-4-morpholinocyclohexyl)amino)quinazolin-6-yl)-1H-pyrazole-4-carboxylate;

6-(2-methyl-1,3-thiazol-4-yl)-N-(trans-4-morpholin-4-ylcyclohexyl)quinazolin-4-amine;

6-[2-(1-methylethyl)-1,3-thiazol-4-yl]-N-(trans-4-morpholin-4-ylcyclohexyl)quinazolin-4-amine;

N-(trans-4-morpholin-4-ylcyclohexyl)-6-[5-(trifluoromethyl)pyridin-3-yl]quinazolin-4-amine;

3-{4-[(trans-4-morpholin-4-ylcyclohexyl)amino]quinazolin-6-yl}-5-(trifluoromethyl)pyridin-2-ol ;

2-chloro-5-{4-[(trans-4-morpholin-4-ylcyclohexyl)amino]quinazolin-6-yl}pyridin-3-ol;

6-(5-amino-6-fluoropyridin-3-yl)-N-(trans-4-morpholin-4-ylcyclohexyl)quinazolin-4-amine;

6-{4-[(trans-4-morpholin-4-ylcyclohexyl)amino]quinazolin-6-yl}pyridine-2-carboxylic acid;

6-(4-fluoro-1H-pyrazol-3-yl)-N-(trans-4-morpholin-4-ylcyclohexyl)quinazolin-4-amine;

4-{4-[(trans-4-morpholin-4-ylcyclohexyl)amino]quinazolin-6-yl}-1H-pyrazole-3-carbonitrile;

5-{4-[(trans-4-morpholin-4-ylcyclohexyl)amino]quinazolin-6-yl}-1H-1,2,3-triazole-4-carbonitrile;

(1-methyl-4-{4-[(trans-4-morpholin-4-ylcyclohexyl)amino]quinazolin-6-yl}-1H-pyrazol-3-yl)methanol;

6-(1-methyl-1H-pyrazol-5-yl)-N-(trans-4-morpholin-4-ylcyclohexyl)quinazolin-4-amine;

N-(trans-4-morpholin-4-ylcyclohexyl)-6-[3-(trifluoromethyl)-1H-pyrazol-4-yl]quinazolin-4-amine;

6-(1-methyl-1H-1,2,3-triazol-5-yl)-N-(trans-4-morpholin-4-ylcyclohexyl)quinazolin-4-amine;

6-(2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

3-(4-{[trans-4-(morpholin-4-yl)cyclohexyl]amino}quinazolin-6-yl)thiophene-2-carbonitrile;

4-(4-{[trans-4-(morpholin-4-yl)cyclohexyl]amino}quinazolin-6-yl)thiophene-3-carbonitrile;

6-(4-methyl-1H-imidazol-5-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

6-(3-methyl-1H-pyrazol-4-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

6-(1,5-dimethyl-1H-pyrazol-4-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

6-(4-methyl-1H-imidazol-2-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

6-(1,4-dimethyl-1H-imidazol-2-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

6-(3,5-dimethyl-1H-pyrazol-4-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

6-(2-methyl-1H-imidazol-4-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

6-(2-cyclopropyl-1-methyl-1H-imidazol-5-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

6-(1-methyl-1H-imidazol-2-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

6-(1-methyl-1H-1,2,4-triazol-5-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

6-(isoxazol-4-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

6-(6-fluoro-5-methoxypyridin-3-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

2-fluoro-5-(4-{[trans-4-(morpholin-4-yl)cyclohexyl]amino}quinazolin-6-yl)pyridin-3-ol;

6-[5-(dimethylamino)-6-fluoropyridin-3-yl]-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

6-[6-fluoro-5-(methylamino)pyridin-3-yl]-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

6-(6-chloro-5-fluoropyridin-3-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

6-(5,6-difluoropyridin-3-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

6-(5-(difluoromethyl)pyridin-3-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

6-(5-amino-6-chloropyridin-3-yl)-N-[trans-4-(morpholin-4-yl)cyclohexyl]quinazolin-4-amine;

5-(4-(((trans)-4-(dimethylamino)cyclohexyl)amino)quinazolin-6-yl)pyridin-3-ol;

N,N-dimethyl-6-(4-(((trans)-4-morpholinocyclohexyl)amino)quinazolin-6-yl)picolinamide;

5-(4-{[trans-4-(4,4-difluoropiperidin-1-yl)cyclohexyl]amino}quinazolin-6-yl)-2-fluoropyridin-3-ol;

5-(4-{[trans-4-(3-methoxyazetidin-1-yl)cyclohexyl]amino}quinazolin-6-yl)pyridin-3-ol;

5-[4-({trans-4-[cyclopropyl(methyl)amino]cyclohexyl}amino)quinazolin-6-yl]pyridin-3-ol;

5-[4-({trans-4-[(2-methoxyethyl)amino]cyclohexyl}amino)quinazolin-6-yl]pyridin-3-ol;

5-(4-{[trans-4-(4-methylpiperazin-1-yl)cyclohexyl]amino}quinazolin-6-yl)pyridin-3-ol;

5-[4-({trans-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]cyclohexyl}amino)quinazolin-6-yl]pyridin-3-ol;

6-[5-(methylamino)pyridin-3-yl]-N-{trans-4-[4-(methylsulfonyl)piperazin-1-yl]cyclohexyl}quinazolin-4-amine;

N-[trans-4-(4,4-difluoropiperidin-1-yl)cyclohexyl]-6-[5-(methylamino)pyridin-3-yl]quinazolin-4-amine;

N-[trans-4-(4-fluoropiperidin-1-yl)cyclohexyl]-6-[5-(methylamino)pyridin-3-yl]quinazolin-4-amine;

6-(5-(methylamino)pyridin-3-yl)-N-{trans-4-[4-(morpholin-4-ylmethyl)piperidin-1-yl]cyclohexyl}quinazolin-4-amine;

6-(5-(methylamino)pyridin-3-yl)-N-{trans-4-[(3R)-3-(morpholin-4-ylmethyl)piperidin-1-yl]cyclohexyl}quinazolin-4-amine;

6-[5-(methylamino)pyridin-3-yl]-N-{trans-4-[(3S)-3-(morpholin-4-ylmethyl)piperidin-1-yl]cyclohexyl}quinazolin-4-amine;

2-fluoro-5-(4-{[trans-4-(4-fluoropiperidin-1-yl)cyclohexyl]amino}quinazolin-6-yl)pyridin-3-ol;

2-fluoro-5-[4-({trans-4-[4-(methylsulfonyl)piperazin-1-yl]cyclohexyl}amino)quinazolin-6-yl]pyridin-3-ol;

6-(5-amino-6-fluoropyridin-3-yl)-N-[trans-4-(4,4-difluoropiperidin-1-yl)cyclohexyl]quinazolin-4-amine;

6-(5-amino-6-fluoropyridin-3-yl)-N-[trans-4-(4-fluoropiperidin-1-yl)cyclohexyl]quinazolin-4-amine;

5-(4-{[trans-4-(4,4-difluoropiperidin-1-yl)cyclohexyl]amino}quinazolin-6-yl)pyridin-3-ol;

5-(4-{[trans-4-(4-fluoropiperidin-1-yl)cyclohexyl]amino}quinazolin-6-yl)pyridin-3-ol;

6-(5-amino-6-fluoropyridin-3-yl)-N-{trans-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]cyclohexyl}quinazolin-4-amine;

6-(5-amino-6-fluoropyridin-3-yl)-N-{trans-4-[4-(methylsulfonyl)piperazin-1-yl]cyclohexyl}quinazolin-4-amine;

6-(5-amino-6-fluoropyridin-3-yl)-N-{trans-4-[3-(morpholin-4-ylmethyl)piperidin-1-yl]cyclohexyl}quinazolin-4-amine;

6-(5-amino-6-fluoropyridin-3-yl)-N-{trans-4-[(2R)-2-(fluoromethyl)morpholin-4-yl]cyclohexyl}quinazolin-4-amine;

6-(5-amino-6-fluoropyridin-3-yl)-N-{trans-4-[(2S)-2-(fluoromethyl)morpholin-4-yl]cyclohexyl}quinazolin-4-amine;

6-(5-amino-6-fluoropyridin-3-yl)-N-{trans-4-[(2R)-2-methylmorpholin-4-yl]cyclohexyl}quinazolin-4-amine;

6-(5-amino-6-fluoropyridin-3-yl)-N-{trans-4-[(2S)-2-methylmorpholin-4-yl]cyclohexyl}quinazolin-4-amine;

N-{trans-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]cyclohexyl}-6-[6-fluoro-5-(methylamino)pyridin-3-yl]quinazolin-4-amine;

N-[trans-4-(4,4-difluoropiperidin-1-yl)cyclohexyl]-6-[6-fluoro-5-(methylamino)pyridin-3-yl]quinazolin-4-amine;

cyclopropyl {4-[trans-4-({6-[6-fluoro-5-(methylamino)pyridin-3-yl]quinazolin-4-yl}amino)cyclohexyl]piperazin-1-yl}methanone;

6-[6-fluoro-5-(methylamino)pyridin-3-yl]-N-[trans-4-(4-fluoropiperidin-1-yl)cyclohexyl]quinazolin-4-amine;

6-[6-fluoro-5-(methylamino)pyridin-3-yl]-N-{trans-4-[(2R)-2-methylmorpholin-4-yl]cyclohexyl}quinazolin-4-amine; and

6-[6-fluoro-5-(methylamino)pyridin-3-yl]-N-{trans-4-[(2S)-2-methylmorpholin-4-yl]cyclohexyl}quinazolin-4-amine;

or a pharmaceutically acceptable salt or stereoisomer thereof.

4. A pharmaceutical composition comprising a pharmaceutical carrier, and dispersed therein, a therapeutically effective amount of a compound of claim 1 .

Assignments (2)
MERGER Recorded Aug 8, 2022
From: MERCK SHARP & DOHME CORP.
To: MERCK SHARP & DOHME LLC
Reel/Frame 061102/0145 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 31, 2017
From: ALTMAN, MICHAEL D.; BRUBAKER, JASON D.; CHILDERS, MATTHEW L.; DONOFRIO, ANTHONY; FISCHMANN, THIERRY; GIBEAU, CRAIG R.; KATTAR, SOLOMON D.; LESBURG, CHARLES A.; LIM, JONGWON; MACLEAN, JOHN K.L.; MANSOOR, UMAR F.; NORTHRUP, ALAN B.; SANDERS, JOHN M.; SMITH, GRAHAM F.; ANDRESEN, BRIAN M.; TORRES, LUIS
To: MERCK SHARP & DOHME CORP.
Reel/Frame 042124/0383 →