US 11,203,600 B2Granted

Kinase inhibitors and uses thereof

AssigneeDenali Therapeutics Inc.

InventorsJavier De Vicente Fidalgo, Anthony A. Estrada, Jianwen A. Feng, Brian Fox, Cinzia Maria Francini, Christopher R. H. Hale, Cheng Hu, Colin Philip Leslie, Maksim Osipov, Elena Serra, Zachary K. Sweeney, Arun Thottumkara

Life of this patent

Estimating the term…

Abstract

The present disclosure relates generally to compounds and compositions, intermediates, processes for their preparation, and their use as kinase inhibitors.

Claims24

Dependent claims

A compound according to Formula I:

or a pharmaceutically acceptable salt, isotopic analog, or isomer thereof, wherein
W1, W3, and W4 are CR7;
W2 is N;
R1a, R1b, and R1c are independently hydrogen, halogen, —CN, —N3, —NO2, —OH, —SF5, —SCF3, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 heteroalkyl, C3-8 cycloalkyl, C1-8 haloalkyl, C1-8 alkoxy, C1-8 haloalkoxy, 4- to 12-membered heterocyclyl, C6-10 aryl, 5- to 12-membered heteroaryl, —N(R1d)2, —C(O)R1e, —C(O)OR1d, —C(O)N(R1d)2, —NR1dC(O)R1e, —NR1dC(O)N(R1d)2, —NR1dC(O)OR1d, —OC(O)N(R1d)2, —OC(O)OR1d, —SR1d, —S(O)R1e, —S(O)2R1e, —S(O)3R1d, —S(O)N(R1d)2, —S(O)2N(R1d)2, —NR1dS(O)R1e, —NR1dS(O)2R1e, —NR1dS(O)N(R1d)2, or —NR1dS(O)2N(R1d)2, wherein each of R1a, R1b, and R1c is optionally and independently substituted with one to eight R5 and at least one of R1a, R1b, and R1c is other than hydrogen;
or
R1b and R1c are optionally taken together to form C3-10 cycloalkyl or 4- to 12-membered heterocyclyl, each of which is optionally substituted with one to eight R5;
or
R1a, R1b, and R1c are optionally taken together to form C5-10 cycloalkyl or 6- to 8-membered heterocyclyl, each of which is optionally substituted with one to eight R5;
each R1d is independently hydrogen, C1-8 alkyl, C1-8 haloalkyl, C3-10 cycloalkyl, or 4- to 12-membered heterocyclyl, or
two R1d on the same atom are optionally taken together to form a 4- to 8-membered heterocyclyl optionally substituted by oxo, halo, or C1-6 alkyl, wherein said alkyl is optionally substituted with one to eight R5;
each R1e is independently C1-8 alkyl, C1-8 haloalkyl, C3-10 cycloalkyl, or 4- to 12-membered heterocyclyl;
R2a and R2b are independently hydrogen, halogen, C1-8 alkyl, C1-8 haloalkyl, C2-8 alkenyl, or C2-8 alkynyl, or
R2a and R2b are optionally taken together to form C3-6 cycloalkyl or 4- to 6-membered heterocyclyl, each of which is optionally substituted with one to eight R6;
R3a and R3b are independently hydrogen, halogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 haloalkyl, C3-6 cycloalkyl, or 4- to 6-membered heterocyclyl, wherein said cycloalkyl and said heterocyclyl are optionally substituted with one to eight R6, or
R3a and R3b are optionally taken together to form oxo, C3-6 cycloalkyl, or 4- to 6-membered heterocyclyl, wherein said cycloalkyl and said heterocyclyl are optionally substituted with one to eight R6;
Y is CR4aR4b;
R4a and R4b are independently hydrogen, halogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 haloalkyl, C3-6 cycloalkyl, or 4- to 6-membered heterocyclyl, wherein said cycloalkyl and said heterocyclyl are optionally substituted with one to eight R6, or
R4a and R4b are optionally taken together to form C3-6 cycloalkyl or 4- to 6-membered heterocyclyl, wherein said cycloalkyl and said heterocyclyl are optionally substituted with one to eight R6, or
R4a and R1b are optionally taken together to form 4- to 12-membered heterocyclyl, which is optionally substituted with one to eight R6, or
R4a and R3a are optionally taken together to form C3-8 cycloalkyl or 4- to 12-membered heterocyclyl, each of which is optionally substituted with one to eight R6,
each R5 is independently halogen, —CN, —OH, —SF5, —SCF3, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 heteroalkyl, C3-8 cycloalkyl, C1-8 alkoxy, 4- to 12-membered heterocyclyl, C6-10 aryl, 5- to 12-membered heteroaryl, (4- to 12-membered heterocyclyl)(C1-8 heteroalkyl), (C6-10 aryl)(C1-8 heteroalkyl), (5- to 12-membered heteroaryl)(C1-8 heteroalkyl), —N(R5a)2, —C(O)R5b, —C(O)OR5a, —C(O)N(R5a)2, —NR5aC(O)R5b, —NR5aC(O)N(R5a)2, —NR5aC(O)OR5a, —OC(O)N(R5a)2, —OC(O)OR5a, —SR5a, —S(O)R5b, —S(O)2R5b, —S(O)3R5a, —S(O)N(R5a)2, —S(O)2N(R5a)2, —NR5aS(O)R5b, —NR5aS(O)2R5b, —NR5aS(O)N(R5a)2, or —NR5aS(O)2N(R5a)2, each of which is optionally substituted with one to eight R5c, or
two R5 are optionally taken together to form oxo;
each R5a is independently hydrogen, C1-8 alkyl, C1-8 haloalkyl, C3-10 cycloalkyl, or 4- to 12-membered heterocyclyl, and
each R5b is independently C1-8 alkyl, C1-8 haloalkyl, C3-10 cycloalkyl, 4- to 12-membered heterocyclyl, or 5- to 12-membered heteroaryl;
each R5c is independently halogen, cyano, C1-8 haloalkyl, C1-8 alkyl, C1-8 alkoxy, C1-8 haloalkoxy, (C1-8 alkoxy)(C1-8 alkoxy), hydroxyl, SR5d, N(R5d)2, N(R5d)2(C1-8 alkoxy), C3-10 cycloalkyl, or 4- to 12-membered heterocyclyl, or
two R5c are optionally taken together to form oxo;
each R5d is independently hydrogen, C1-8 alkyl, or C1-8 haloalkyl;
each R6 is halogen, —CN, —OH, C1-8 alkyl, C1-8 heteroalkyl, C3-8 cycloalkyl, C1-8 haloalkyl, C1-8 alkoxy, 4- to 12-membered heterocyclyl, C6-10 aryl, 5- to 12-membered heteroaryl, —N(R6a)2, —C(O)R6b, —C(O)N(R6a)2, or —C(O)OR6a, or
two R6 are taken together to form oxo;
each R6a is independently hydrogen, C1-8 alkyl, or C1-8 haloalkyl, or
two R6a on the same atom are optionally taken together to form 4- to 6-membered heterocyclyl;
each R6b is independently C1-8 alkyl or C1-8 haloalkyl;
each R7 is independently hydrogen, halogen, —CN, —N3, —NO2, —SF5, —SCF3, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 heteroalkyl, C3-8 cycloalkyl, C1-8 haloalkyl, 4- to 12-membered heterocyclyl, C6-10 aryl, 5- to 12-membered heteroaryl, —OR7a, —C(O)R7b, —N(R7a)2, —C(O)OR7a, —C(O)N(R7a)2, —NR7aC(O)R7b, —NR7aC(O)N(R7a)2, —NR7aC(O)OR7a, —OC(O)N(R7a)2, —OC(O)OR7a, —SR7a, —S(O)R7b, —S(O)2R7b, —S(O)3R7a, —S(O)N(R7a)2, —S(O)2N(R7a)2, —NR7aS(O)R7b, —NR7aS(O)2R7b, —NR7aS(O)N(R7a)2, or —NR7aS(O)2N(R7a)2, each of which is optionally and independently substituted with one to eight R8;
each R7a is independently hydrogen, C1-8 alkyl, C1-8 haloalkyl, C3-10 cycloalkyl, or 4- to 12-membered heterocyclyl, or
two R7a on the same atom are optionally taken together to form a 4- to 8-membered heterocyclyl optionally substituted by oxo, halo, or C1-6 alkyl, wherein said alkyl is optionally substituted with one to eight R8;
each R7b is independently C1-8 alkyl, C1-8 haloalkyl, C3-10 cycloalkyl, or 4- to 12-membered heterocyclyl;
each R8 is halogen, —CN, —OH, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 heteroalkyl, C3-8 cycloalkyl, C1-8 haloalkyl, C1-8 alkoxy, 4- to 12-membered heterocyclyl, C6-10 aryl, 5- to 12-membered heteroaryl, —N(R8a)2, —C(O)R8b, or —C(O)OR8a, or
two R8 are optionally taken together to form oxo;
each R8a is independently hydrogen, C1-8 alkyl, or C1-8 haloalkyl;
each R8b is independently C1-8 alkyl or C1-8 haloalkyl;
and
Z is O.

39 more elements

A compound selected from

Name
Structure
4-(3,3-difluoro-2,2-dimethyl-propanoyl)- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbontrile
4-(2-cyclopropyl-2-methyl-propanoyl)- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(3-cyano-2,2-dimethyl-propanoyl)-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
1-(2,3-dihydropyrido[3,4- f][1,4]oxazepin-4(5H)-yl)-3,3-difluoro- 2,2-dimethylpropan-1-one
4-[1-(5-fluoropyrimidin-2-yl)-4-methyl- piperidine-4-carbonyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-(4-methyltetrahydropyran-4-carbonyl)- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(3-methyltetrahydrofuran-3-carbonyl)- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(2-methoxy-2-methyl-propanoyl)-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-(bicyclo [1.1.1]pentane-3-carbonyl)- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(3,3,3-trifluoro-2,2-dimethyl- propanoyl)-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(1-cyclopropylcyclopropanecarbonyl)- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(4,4,4-trifluoro-2,2-dimethyl- butanoyl)-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[1- (trifluoromethyl)cyclopropanecarbonyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[1- (difluoromethyl)cyclobutanecarbonyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(2,2-difluoro-1-methyl- cyclopropanecarbonyl)-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[2,2-dimethyl-3- (trifluoromethoxy)propanoyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
(3R)-4-(3,3-difluoro-2,2-dimethyl- propanoyl)-3-methyl-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[1- (trifluoromethyl)cyclobutanecarbonyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(2,2-dimethylbutanoyl)-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
3,3-difluoro-1-(9-fluoro-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepin-4-yl)-2,2- dimethyl-propan-1-one
4-(2-cyclopropyl-3,3-difluoro-2-methyl- propanoyl)-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(2-(difluoromethyl)-2- methylbutanoyl)-2,3,4,5- tetrahydropyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-(3-cyclopropyl-2,2-dimethyl- propanoyl)-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
8-chloro-4-(3,3-difluoro-2,2-dimethyl- propanoyl)-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(4-fluoro-2,2-dimethyl-butanoyl)-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
1-(9-chloro-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)-3,3-difluoro-2,2- dimethyl-propan-l-one
3,3-difluoro-2,2-dimethyl-1-(9-methyl- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)propan-l-one
4-(1-ethylcyclopropanecarbonyl)-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-(1-ethylcyclobutanecarbonyl)-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-[(1S,2R)-1,2- dimethylcyclopropanecarbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
3,3-difluoro-2,2-dimethyl-1-[8- (trifluoromethyl)-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepin-4-yl]propan- 1-one
4-[2-methyl-2- (trifluoromethyl)butanoyl]-3,5-dihydro- 2H-pyrido[3,4f][1,4]oxazepine-9- carbonitrile
4-[2-methyl-2- (trifluoromethoxy)propanoyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-(9-fluoro-2,3-dihydropyrido[3,4- f][1,4]oxazepin-4(5H)-yl)-3,3-dimethyl- 4-oxobutanenitrile
4-(9-fluoro-2,3-dihydropyrido[3,4- f][1,4]oxazepin-4(5H)-yl)-2,3,3- trimethyl-4-oxobutanenitrile
4-(3-cyano-2,2-dimethylpropanoyl)- 2,3,4,5-tetrahydropyrido[3,4- f][1,4]oxazepine-9-carbonitrile
3-(9-fluoro-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-4-carbonyl)-3-methyl- pentanenitrile
4-[2-(cyanomethyl)-2-methyl-butanoyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
(3R)-4-(2,2-dimethylbutanoyl)-3-methyl- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
(3R)-3-methyl-4-(2-methylbutanoyl)-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
(3R)-4-(3-fluoro-2,2-dimethyl- propanoyl)-3-methyl-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
(3R)-4-(2,2-dimethylpropanoyl)-3- methyl-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
3,3,3-trifluoro-1-(9-fluoro-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepin-4-yl)-2,2- dimethyl-propan-1-one
1-(9-fluoro-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)-2,2-dimethyl- propan-1-one
4-(2-(1-hydroxycyclopropyl)-2- methylpropanoyl)-2,3,4,5- tetrahydropyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[2-(-2-(difluoromethyl)cyclopropyl)-2- methyl-propanoyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[2-(2-cyanocyclopropyl)-2-methyl- propanoyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[2-(3,3-difluorocyclobutyl)-2-methyl- propanoyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[2-[1-(5-fluoropyrimidin-2-yl)azetidin- 3-yl]-2-methyl-propanoyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
(3R)-4-[4-fluoro-1-(5-fluoropyrimidin-2- yl)piperidine-4-carbonyl]-3-methyl-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-(4-fluoro-1-pyrazin-2-yl-piperidine-4- carbonyl)-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(4-fluoro-l-pyrimidin-4-yl-piperidine- 4-carbonyl)-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(cis-3-(5-fluoropyrimidin-2-yl)-3- azabicyclo[4.1.0]heptane-6-carbonyl)- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[2-[1-(5-fluoropyrimidin-2- yl)pyrrolidin-3-yl]-2-methyl-propanoyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[1-(5-fluoropyrimidin-2-yl)-2-methyl- piperidine-4-carbonyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[1-(5-fluoropyrimidin-2-yl)azepane- 4-carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(3-(((5-fluoropyrimidin-2- yl)oxy)methyl)bicyclo[1.1.1]pentane-1- carbonyl)-2,3,4,5-tetrahydropyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[4-(difluoromethyl)-1-(5- fluoropyrimidin-2-yl)piperidine-4- carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[4-fluoro-1-(pyridine-3- carbonyl)piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-[3,3-difluoro-1-(5-fluoropyrimidin-2- y1)-4-methyl-piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-(4-fluoro-1-quinazolin-2-yl-piperidine- 4-carbonyl)-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[4-ethyl-1-(5-fluoropyrimidin-2- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[7,7-difluoro-3-(5-fluoropyrimidin-2- yl)-3-azabicyclo[4.1.0]heptane-6- carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[1-(5-cyclopropylpyrimidin-2-yl)-4- fluoro-piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-[4-fluoro-1-(5-methoxypyrimidin-2- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[1-[5-(difluoromethoxy)pyrimidin-2- y1]-4-fluoro-piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-[4-fluoro-1-(4-methoxypyrimidin-2- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
(3R)-4-(1-(5-fluoropyrimidin-2- yl)piperidine-4-carbonyl)-3-methyl- 2,3,4,5-tetrahydropyrido[3,4- f][1,4]oxazepine-9-carbonitrile
(3R)-4-[1-(5-fluoropyrimidin-2-yl)-4- methoxy-piperidine-4-carbonyl]-3- methyl-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(4-fluoro-1-imidazo[1,2-a]pyrazin-8- yl-piperidine-4-carbonyl)-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[4-fluoro-1-(1-methylpyrazolo[4,3- c]pyridin-6-yl)piperidine-4-carbonyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[4-fluoro-1-(5-methylpyrrolo[3,2- d]pyrimidin-2-yl)piperidine-4-carbonyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(4-fluoro-1-imidazo[1,2-b]pyridazin-6- yl-piperidine-4-carbonyl)-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-(4-fluoro-1-(pyrazolo[1,5-a]pyrimidin- 7-yl)piperidine-4-carbonyl)-2,3,4,5- tetrahydropyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[1-(6,7-dihydro-5H- cyclopenta[d]pyrimidin-2-yl)-4-fluoro- piperidine-4-carbonyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-(4-fluoro-1-(5-fluoropyrimidin-4- yl)piperidine-4-carbonyl)-2,3,4,5- tetrahydropyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[4-fluoro-1-(3-fluoro-2- pyridyl)piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-[4-fluoro-1-(5-fluoro-2-methoxy- pyrimidin-4-yl)piperidine-4-carbonyl]- 3,5-dihydro-2H-pyrido[3,4- f[[1,4]oxazepine-9-carbonitrile
4-[4-fluoro-1-(6-methoxypyridazin-3- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-(4-fluoro-1-pyridazin-3-yl-piperidine- 4-carbonyl)-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[1-(4-methoxypyrimidin-2- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[1-(5-fluoro-4-methoxy-pyrimidin-2- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
(3R)-4-(1-(4-methoxypyrimidin-2- yl)piperidine-4-carbonyl)-3-methyl- 2,3,4,5-tetrahydropyrido[3,4- f][1,4]oxazepine-9-carbonitrile
(3R)-4-(1-(5-fluoro-4- methoxypyrimidin-2-yl)piperidine-4- carbonyl)-3-methyl-2,3,4,5- tetrahydropyrido[3,4-f][1,4]oxazepine-9- carbonitrile
(9-fluoro-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)[1-(5 fluoropyrimidin-2-yl)-4-methoxy-4- piperidyl]methanone
(9-fluoro-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)-[1-(5-fluoro-4- methoxy-pyrimidin-2-yl)-4-methoxy-4- piperidyl]methanone
4-[4-fluoro-1-[5-fluoro-4- (methylamino)pyrimidin-2-yl]piperidine- 4-carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[1-[4-(cyclopropylamino)-5-fluoro- pyrimidin-2-yl]-4-fluoro-piperidine-4- carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[1-[4-(2,2-difluoroethoxy)-5-fluoro- pyrimidin-2-yl]-4-fluoro-piperidine-4- carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[4-fluoro-1-(5-fluoro-4- methylsulfanyl-pyrimidin-2- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[1-[4-[3-(dimethylamino)propoxy]-5- fluoro-pyrimidin-2-yl]-4-fluoro- piperidine-4-carbonyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[1-(5-chloro-4-methoxy-pyrimidin-2- yl)-4-fluoro-piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-[1-(5-chloro-4-methoxy-pyrimidin-2- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
(9-fluoro-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)-[1-[5-fluoro-4-(2- methoxyethoxy)pyrimidin-2-yl]-4- piperidyl]methanone
4-(1-(4-(2,2-difluoroethoxy)-5- fluoropyrimidin-2-yl)piperidine-4- carbonyl)-2,3,4,5-tetrahydropyrido[3,4- f][1,4]oxazepine-9-carbonitrile
(1-(4-(2,2-difluoroethoxy)-5- fluoropyrimidin-2-yl)-4- methoxypiperidin-4-yl)(9-fluoro-2,3- dihydropyrido[3,4-f][1,4]oxazepin- 4(5H)-yl)methanone
4-[1-[4-(2,2-difluoroethoxy)pyrimidin-2- yl]piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
[1- [4-(2,2-difluoroethoxy)pyrimidin-2- yl]-4-methoxy-4-piperidyl]-(9-fluoro- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)methanone
(9-fluoro-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)-(4-methoxy-1- pyrimidin-2-yl-4-piperidyl)methanone
[1- [4-[2-(dimethylamino)ethoxy]-5- fluoro-pyrimidin-2-yl]-4-methoxy-4- piperidyl]-(9-fluoro-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepin-4- yl)methanone
4-(4-(fluoromethyl)-1-(5- fluoropyrimidin-2-yl)piperidine-4- carbonyl)-2,3,4,5-tetrahydropyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(3,3-difluoro-1-methyl- cyclobutanecarbonyl)-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-(1-(difluoromethyl)cyclopropane-1- carbonyl)-2,3,4,5-tetrahydropyrido]3,4- f][1,41oxazepine-9-carbonitrile
4-(1-fluorocyclopropanecarbonyl)-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-(4,4,4-trifluoro-2-methyl-butanoyl)- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(3,3-difluoro-2,2-dimethyl-butanoyl)- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(2,2,3,3,4,4,4,-heptafluorobutanoyl)- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(3-fluoro-2,2-dimethyl-propanoyl)-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-(2,2,3-trimethylbutanoyl)-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-(2-cyclopropylpropanoyl)-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[3-fluoro-2-(fluoromethyl)-2-methyl- propanoyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(2-methyl-2-methylsulfanyl- propanoyl)-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(4,4-difluoro-2,2-dimethyl-butanoyl)- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(3-methoxy-2,2-dimethyl-propanoyl)- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(2-ethyl-2-methyl-butanoyl)-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-[3,3,3-trifluoro-2-methyl-2- (trifluoromethyl)propanoyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-(2-methoxy-2-methyl-butanoyl)-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-(2-cyclopropyl-2-methoxy-propanoyl)- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[1-(5-fluoropyrimidin-2-yl)piperidine- 4-carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
(9-fluoro-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)-[1-(5- fluoropyrimidin-2-yl)-4- piperidyl]methanone
4-(4-fluoro-1-pyrimidin-2-yl-piperidine- 4-carbonyl)-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(2-chloro-2-methyl-propanoyl)-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
2-[4-fluoro-4-(9-fluoro-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-4-carbonyl)-1- piperidyl]pyrimidine-5-carbonitrile
2-[4-fluoro-4-(9-fluoro-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-4-carbonyl)- 1-piperidyl]pyrimidine-4-carbonitrile
4-[4-fluoro-1-(5-fluoropyrimidin-2- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[4-fluoro-1-(4-methylpyrimidin-2- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[4-fluoro-1-(5-methylpyrimidin-2- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[1-(5-chloropyrimidin-2-yl)-4-fluoro- piperidine-4-carbonyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[1-(5,7-dihydrofuro[3,4-d]pyrimidin-2- y1)-4-fluoro-piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-[4-fluoro-1-([1,2,4]triazolo[1,5- c]pyrimidin-5-yl)piperidine-4-carbonyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[4-fluoro-1-[4- (trifluoromethyl)pyrimidin-2- yl]piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[4-fluoro-1-[4-methyl-6- (trifluoromethyl)pyrimidin-2- yl]piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[4-fluoro-1-(9-methylpurin-2- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[4-fluoro-1-[5- (trifluoromethyl)pyrimidin-2- yl]piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[4-fluoro-1-[2- (trifluoromethyl)pyrimidin-4- yl]piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[4-fluoro-1-(2-methoxypyrimidin-4- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[4-fluoro-1-(5-methyloxazole-4- carbonyl)piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
isobutyl 4-(9-cyano-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-4-carbonyl)- 4-fluoro-piperidine-1-carboxylate
4-(2,2-dimethylpropanoyl)-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[3-fluoro-1-(5-fluoropyrimidin-2- yl)pyrrolidine-3-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[4-chloro-1-(5-fluoropyrimidin-2- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[1-(4-ethoxy-5-fluoro-pyrimidin-2-yl)- 4-fluoro-piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-[4-fluoro-1-(8-fluoro- [1,2,4]triazolo[1,5-c]pyrimidin-5- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-(4-fluoro-1-imidazo[1,2-a]pyrimidin-5- yl-piperidine-4-carbonyl)-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-(3-((5-fluoropyrimidin-2-yl)thio)-2,2- dimethylpropanoyl)-2,3,4,5- tetrahydropyrido[3,4-f][1,41oxazepine-9- carbonitrile
4-[4-cyano-1-(5-fluoropyrimidin-2- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[4-fluoro-1-(5-fluoro-4-methyl- pyrimidin-2-yl)piperidine-4-carbonyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[1-(5-fluoropyrimidin-2-yl)-4- methoxy-piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[1-(2-chloro-5-methoxy-pyrimidin-4- y1)-4-fluoro-piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-[1-(5-fluoropyrimidin-2-yl)-3-methyl- piperidine-4-carbonyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[4-fluoro-1-(5-fluoro-2- pyridyl)piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-[1-[5-(difluoromethyl)pyrimidin-2-yl] 4-fluoro-piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-[1-(5-fluoro-2-pyridyl)-4-methoxy- piperidine-4-carbonyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[4-fluoro-1-(5-fluoro-4-methoxy- pyrimidin-2-yl)piperidine-4-carbonyl] 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[1-(3,5-difluoro-2-pyridyl)-4-fluoro- piperidine-4-carbonyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[1-(5,6-difluoro-3-pyridyl)-4-fluoro- piperidine-4-carbonyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[1-(5-fluoro-4-methoxy-pyrimidin-2- yl)-4-methoxy-piperidine-4-carbonyl] 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[1-(5-fluoro-4-methoxy-6-methyl- pyrimidin-2-yl)-4-methoxy-piperidine-4- carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[4-fluoro-1-(5-fluoro-4-methoxy-6- methyl-pyrimidin-2-yl)piperidine-4- carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[4-fluoro-1-(4-methoxyquinazolin-2- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-(4-fluoro-1-quinoxalin-2-yl-piperidine- 4-carbonyl)-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[4-fluoro-1-(3-isoquinolyl)piperidine- 4-carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[4-fluoro-1-(2-quinolyl)piperidine-4- carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[1-(4-cyclopropyl-5-fluoro-pyrimidin- 2-yl)-4-fluoro-piperidine-4-carbonyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[1-(2-chloro-5-fluoro-pyrimidin-4-yl)- 4-fluoro-piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-[1-(8-fluoro-[1,2,4]triazolo[1,5- c]pyrimidin-5-yl)piperidine-4-carbonyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9carbonitrile
4-(1-pyrazolo[1,5-a]pyrimidin-7- ylpiperidine-4-carbonyl)-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[4-fluoro-1-([1,2,4]triazolo[1,5- a]pyrazin-8-yl)piperidine-4-carbonyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
1-(9-fluoro-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)-2,2-dimethyl- butan-1-one
4-[3-fluoro-1-(5-fluoropyrimidin-2-yl)-4- hydroxy-piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
[1-[4-(2,2-difluoroethoxy)-1,3,5-triazin- 2-yl]-4-methoxy-4-piperidy1]-(9-fluoro- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)methanone
[1-[4-(2,2-difluoroethoxy)-1,3,5-triazin- 2-yl]-4-piperidy1]-(9-fluoro-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepin-4- yl)methanone
4-[1-(5-fluoropyrimidin-2-yl)-3-hydroxy- piperidine-4-carbonyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[4-fluoro-1-([1,2,4]triazolo[1,5- a]pyrimidin-7-yl)piperidine-4-carbonyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[3,3,4-trifluoro-1-(5-fluoropyrimidin- 2-yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[3,3-difluoro-4-methyl-1-pyrimidin-2- yl-piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-(1-(5-chloropyrimidin-2-yl)-3,3- difluoro-4-methylpiperidine-4-carbonyl)- 2,3,4,5-tetrahydropyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[3,3-difluoro-1-(5-fluoro-6-oxo-1H- pyrimidin-2-yl)-4-methyl-piperidine-4- carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[3,3-difluoro-1-[5-fluoro-4-(2- methoxyethoxy)pyrimidin-2-yl]-4- methyl-piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-(3,3-difluoro-1-(imidazo[2,1- f][1,2,4]triazin-4-yl)piperidine-4- carbonyl)-2,3,4,5-tetrahydropyridol3,4- f][1,4]oxazepine-9-carbonitrile
4-[3,3-difluoro-1-([1,2,4]triazolo[1,5- a]pyrazin-8-yl)piperidine-4-carbonyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(3,3-difluoro-1-pyrazolo[1,5- a][1,3,5]triazin-4-yl-piperidine-4- carbonyl)-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(3,3-difluoro-1-pyrazolo[1,5- a]pyrimidin-7-yl-piperidine-4-carbonyl)- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[3,3-difluoro-4-methyl-1- ([1,2,4]triazolo[1,5-a]pyrazin-8- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[(3,4)-trans-3-fluoro-1-(5- fluoropyrimidin-2-yl)-4-methyl- piperidine-4-carbonyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[(3,4)-trans-3-fluoro-1-(2-methyl-3- oxo-pyridazin-4-yl)piperidine-4- carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[(3,4)-trans-3-fluoro-1- ([1,2,4]triazolo[1,5-a]pyrazin-8- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[(3,4)-trans-3-fluoro-1-(3- fluoropyrazolo[1,5-a]pyrimidin-7- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[1-(3-chloropyrazolo[1,5-a]pyrimidin- 7-yl)-(3,4)-trans-3-fluoro-piperidine-4- carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[1-(3-fluoropyrazolo[1,5-a]pyrimidin-7- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[1-(3-chloropyrazolo[1,5-a]pyrimidin- 7-yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[1-(5-fluoropyrimidin-2-yl)piperidine- 4-carbonyl]spiro[2,5-dihydropyrido[3,4- f][1,4]oxazepine-3,1′-cyclopropane]-9- carbonitrile
4-[4-(5-fluoropyrimidin-2-yl)-1,4- oxazepane-7-carbonyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[4-fluoro-1-[4-methoxy-6- (trifluoromethyl)pyrimidin-2- yl]piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[1-(4-cyclopropyl-5-fluoro-pyrimidin- 2-yl)-4-methoxy-piperidine-4-carbonyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl-[1-(5- fluoropyrimidin-2-yl)-4-methoxy-4- piperidyl]methanone
3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl41-(5-fluoro-4- methoxy-pyrimidin-2-yl)-4-methoxy-4- piperidyl]methanone
(9-fluoro-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)-[1-(5-fluoro-4- methoxy-pyrimidin-2-yl)-4- piperidyl]methanone
3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl41-(5-fluoro-4- methoxy-pyrimidin-2-yl)-4- piperidyl]methanone
4-(4-methoxy-1-pyrimidin-2-yl- piperidine-4-carbonyl)-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-(2-methyltetrahydropyran-2-carbonyl)- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[(3,4)-cis-3-fluoro-1-(5- fluoropyrimidin-2-yl)piperidine-4- carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[(3,4)-trans-3-fluoro-1-(5- fluoropyrimidin-2-yl)piperidine-4- carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[3,3-difluoro-1-(5-fluoropyrimidin-2- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
[3,3-difluoro-1-(5-fluoropyrimidin-2-yl)- 4-methyl-4-piperidyl]-(3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepin-4- yl)methanone
4-[1-(5-fluoropyrimidin-2-yl)-3,6- dihydro-2H-pyridine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-[3,3-difluoro-1-([1,2,4]triazolo[1,5- c]pyrimidin-5-yl)piperidine-4-carbonyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
((3R,4R)-3-fluoro-1-(5-fluoropyrimidin- 2-yl)piperidin-4-yl)(9-fluoro-2,3- dihydropyrido[3,4-f][1,41oxazepin- 4(5H)-yl)methanone
(9-fluoro-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)-[1-(5- fluoropyrimidin-2-yl)-3,6-dihydro-2H- pyridin-4-yl]methanone
4-[(3,4)-trans-3-fluoro-l-pyrazolo[1,5- a]pyrimidin-7-yl-piperidine-4-carbonyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[(3,4)-trans-3-fluoro-1- ([1,2,4]triazolo[1,5-c]pyrimidin-5- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
[3,3-difluoro-1-([1,2,4]triazolo[1,5- c]pyrimidin-5-yl)-4-piperidyl]-(9-fluoro- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)methanone
(3,3-difluoro-1-pyrazolo[1,5- a]pyrimidin-7-yl-4-piperidy1)-(9-fluoro- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)methanone
(9-fluoro-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)-[(3,4)-trans-3- fluoro-1-pyrazolo[1,5-a]pyrimidin-7-yl- 4-piperidyl]methanone
3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl-[(3,4)-trans-3 fluoro-1-(5-fluoropyrimidin-2-yl)-4- piperidyl]methanone
(9-fluoro-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)-[(3,4)-trans-3- fluoro-1-([1,2,4]triazolo [1,5-c]pyrimidin- 5-yl)-4-piperidyl]methanone
(9-fluoro-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)-[(3,4)-trans-3- fluoro-1-(3-fluoropyrazolo[1,5- a]pyrimidin-7-yl)-4-piperidyl]methanone
(9-fluoro-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepin-4-yl)-[(3,4)-trans-3- fluoro-1-([1,2,4]triazolo[1,5-a]pyrazin-8- yl)-4-piperidyl]methanone
4-[((2S)-2-cyclopropyl-3,3-difluoro-2- methyl-propanoyl)]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[((2R)-2-cyclopropyl-3,3-difluoro-2- methyl-propanoyl)]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[((2S)-2-(difluoromethyl)-2- methylbutanoyl)]-2,3,4,5- tetrahydropyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[((2R)-2-(difluoromethyl)-2- methylbutanoyl)]-2,3,4,5- tetrahydropyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-(3,3-difluoro-2,2-dimethyl-propanoyl)- 8-methyl-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
2,2,3,3-tetradeuterio-4-(3,3-difluoro-2,2- dimethyl-propanoyl)-5H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[(2S)-2-(cyanomethyl)-2-methyl- butanoyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[(2R)-2-(cyanomethyl)-2-methyl- butanoyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[3,3-difluoro-2-(fluoromethyl)-2- methyl-propanoyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[3,3-difluoro-2-(fluoromethyl)-2- methyl-butanoyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[2-(difluoromethyl)-3,3-difluoro-2- methyl-propanoyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[2-(difluoromethyl)-3,3-difluoro-2- methyl-butanoyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-(3-fluoro-2,2-dimethyl-butanoyl)-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-(2,2-dimethylbut-3-enoyl)-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[(3S)-3-fluoro-2,2-dimethyl-butanoyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[(3R)-3-fluoro-2,2-dimethyl- butanoyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-(2-methyl-2-(2- ((trifluoromethoxy)methyl)cyclopropyl) propanoyl)-2,3,4,5-tetrahydropyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[2-methyl-2-[3-(triazol-2- yl)cyclobutyl]propanoyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[2-methyl-2-[3-(triazol-1- yl)cyclobutyl]propanoyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[2-[3 -(4-fluoropyrazol-1- yl)cyclobutyl]-2-methyl-propanoyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-[2-(3-chlorocyclobutyl)-2-methyl- propanoyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[2-methyl-2- [3- (trifluoromethoxy)cyclobutyl]propanoyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[2-[(3S)-1-(5-fluoropyrimidin-2- yl)pyrrolidin-3-yl]-2-methyl-propanoyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[2-[(3R)-1-(5-fluoropyrimidin-2- yl)pyrrolidin-3-yl]-2-methyl-propanoyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[(2S)-2-methoxy-2-methyl-butanoyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[(2R)-2-methoxy-2-methyl- butanoyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[(4R)-3,3-difluoro-1-(5- fluoropyrimidin-2-yl)-4-methyl- piperidine-4-carbonyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[(4S)-3,3-difluoro-1-(5- fluoropyrimidin-2-yl)-4-methyl- piperidine-4-carbonyl]-3,5-dihydro-2H- pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[1-(6,7-dihydro-5H-pyrrolo[3,4- b]pyridin-2-yl)-4-fluoro-piperidine-4- carbonyl]-3,5 -dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[1-(3,5-difluoro-6-methoxy-2- pyridyl)piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-[1-(3,5,6-trifluoro-2- pyridyl)piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-[1-(3,5-difluoro-6-methoxy-2-pyridyl)- 4-methoxy-piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-][1,4]oxazepine- 9-carbonitrile
trans-4-[2-methyl-2-[3 -(triazol-2- ylmethyl)cyclobutyl]propanoyl]-3,5- dihydro-2H-pyrido[3,4-][1,4]oxazepine- 9-carbonitrile
cis-4-[2-methyl-2-[3 -(triazol-2- ylmethyl)cyclobutyl]propanoyl]-3,5- dihydro-2H-pyrido[3,4-][1,4]oxazepine- 9-carbonitrile
trans-4-[2-methyl-2-[3-(triazol-1- ylmethyl)cyclobutyl]propanoyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
cis-4-[2-methyl-2-[3-(triazol-1- ylmethyl)cyclobutyl]propanoyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
4-[4-fluoro-1-(5-fluoro- [1,2,4]triazolo[1,5-a]pyrazin-8- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[(4S)-3,3,4-trifluoro-1-(5- fluoropyrimidin-2-yl)piperidine-4- carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[(4R)-3,3,4-trifluoro-1-(5- fluoropyrimidin-2-yl)piperidine-4- carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[(4R)-3,3 -difluoro-4-methyl- pyrimidin-2-yl-piperidine-4-carbonyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[(4S )-3,3 -difluoro-4-methyl-1- pyrimidin-2-yl-piperidine-4-carbonyl]- 3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[(3 S ,4R)-3-fluoro-1-(5- fluoropyrimidin-2-yl)-4-methyl- piperidine-4-carbonyl]-3,5-dihydro-2H- pyrido[3,4-][1,4]oxazepine-9- carbonitrile
4-[(3R,4S)-3-fluoro-1-(5- fluoropyrimidin-2-yl)-4-methyl- piperidine-4-carbonyl]-3,5-dihydro-2H- pyrido[3,4-][1,4]oxazepine-9- carbonitrile
4-[(3R,4R)-3-fluoro- ([1,2,4]triazolo[1,5-a]pyrazin-8- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-][1,4]oxazepine-9- carbonitrile
4-[(3 S ,4S)-3-fluoro-1- ([1,2,4]triazolo[1,5-a]pyrazin-8- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-][1,4]oxazepine-9- carbonitrile
4-[(3R,4R)-3-fluoro-1-(3- fluoropyrazolo[1,5-a]pyrimidin-7- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[(3S,4S)-3-fluoro-1-(3- fluoropyrazolo[1,5-a]pyrimidin-7- yl)piperidine-4-carbonyl]-3,5-dihydro- 2H-pyrido[3,4-f][1,4]oxazepine-9- carbonitrile
4-[(3R,4R)-3-fluoro-1-(5- fluoropyrimidin-2-yl)piperidine-4- carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[(3S,4S)-3-fluoro-1-(5- fluoropyrimidin-2-yl)piperidine-4- carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[(4R)-3,3-difluoro-1-(5- fluoropyrimidin-2-yl)piperidine-4- carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[(4S)-3,3-difluoro-1-(5- fluoropyrimidin-2-yl)piperidine-4- carbonyl]-3,5-dihydro-2H-pyrido[3,4- f][1,4]oxazepine-9-carbonitrile
4-[1-(5-fluoropyrimidin-2-yl)-3- methoxy-piperidine-4-carbonyl]-3,5- dihydro-2H-pyrido[3,4-f][1,4]oxazepine- 9-carbonitrile
or a pharmaceutically acceptable salt, isotopic analog, or isomer thereof.

270 more elements

A method for preparing a compound according to Formula A:

or a salt thereof, the method comprising:
contacting a compound according to Formula IIa
with a compound according to Formula IIb,
under conditions sufficient to form a compound according to Formula IIc
converting the compound of Formula IIc to a compound of Formula IId
and contacting the compound of Formula IId with a compound of Formula IIe
under conditions sufficient to form the compound of Formula A;
wherein:
Z1 is an optionally protected first reactive group;
Z2 is an optionally protected second reactive group;
Q is —OH or a leaving group;
and
W1, W3, and W4 are independently CR7;
W2 is N;
R1a, R1b, and R1c are independently hydrogen, halogen, —CN, —N3, —NO2, —OH, —SF5, —SCF3, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 heteroalkyl, C3-8 cycloalkyl, C1-8 haloalkyl, C1-8 alkoxy, C1-8 haloalkoxy, 4- to 12-membered heterocyclyl, C6-10 aryl, 5- to 12-membered heteroaryl, —N(R1d)2, —C(O)R1e, —C(O)OR1d, —C(O)N(R1d)2, —NR1dC(O)R1e, —NR1dC(O)N(R1d)2, —NR1dC(O)OR1d, —OC(O)N(R1d)2, —OC(O)OR1d, —SR1d, —S(O)R1e, —S(O)2R1e, —S(O)3R1d, —S(O)N(R1d)2, —S(O)2N(R1d)2, —NR1dS(O)R1e, —NR1dS(O)2R1e, —NR1dS(O)N(R1d)2, or —NR1dS(O)2N(R1d)2, wherein each of R1a, R1b, and R1c is optionally and independently substituted with one to eight R5 and at least one of R1a, R1b, and R1c is other than hydrogen;
or
R1b and R1c are optionally taken together to form C3-10 cycloalkyl or 4- to 12-membered heterocyclyl, each of which is optionally substituted with one to eight R5;
or
R1a, R1b, and R1c are optionally taken together to form C5-10 cycloalkyl or 5- to 12-membered heterocyclyl, each which is optionally substituted with one to eight R5;
or
R1a is absent and R1b and R1c are taken together to form C6-10 aryl or 5- to 12-membered heteroaryl or 5- to 12-membered heterocyclyl, each of which is optionally substituted with one to eight R5;
each R1d is independently hydrogen, C1-8 alkyl, C1-8 haloalkyl, C3-10 cycloalkyl, or 4- to 12-membered heterocyclyl, or
two R1d on the same atom are optionally taken together to form a 4- to 8-membered heterocyclyl optionally substituted by oxo, halo, or C1-6 alkyl, wherein said alkyl is optionally substituted with one to eight R5;
each R1e is independently C1-8 alkyl, C1-8 haloalkyl, C3-10 cycloalkyl, or 4- to 12-membered heterocyclyl;
R2a and R2b are independently hydrogen, halogen, C1-8 alkyl, C1-8 haloalkyl, C2-8 alkenyl, or C1-8 alkynyl, or
R2a and R2b are optionally taken together to form C3-6 cycloalkyl or 4- to 6-membered heterocyclyl, each of which is optionally substituted with one to eight R6;
R3a and R3b are independently hydrogen, halogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 haloalkyl, C3-6 cycloalkyl, or 4- to 6-membered heterocyclyl, wherein said cycloalkyl and said heterocyclyl are optionally substituted with one to eight R6, or
R3a and R3b are optionally taken together to form oxo, C3-6 cycloalkyl, or 4- to 6-membered heterocyclyl, wherein said cycloalkyl and said heterocyclyl are optionally substituted with one to eight R6;
Y is CR4aR4b;
R4a and R4b are independently hydrogen, halogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 haloalkyl, C3-6 cycloalkyl, or 4- to 6-membered heterocyclyl, wherein said cycloalkyl and said heterocyclyl are optionally substituted with one to eight R6, or
R4a and R4b are optionally taken together to form C3-6 cycloalkyl or 4- to 6-membered heterocyclyl, wherein said cycloalkyl and said heterocyclyl are optionally substituted with one to eight R6, or
R4a and R1b are optionally taken together to form 4- to 12-membered heterocyclyl, which is optionally substituted with one to eight R6, or
R4a and R3a are optionally taken together to form C3-8 cycloalkyl or 4- to 12-membered heterocyclyl, each of which is optionally substituted with one to eight R6;
each R5 is independently halogen, —CN, —OH, —SF5, —SCF3, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 haloalkyl, C1-8 heteroalkyl, C3-8 cycloalkyl, C1-8 haloalkyl, C1-8 alkoxy, C1-8 haloalkoxy, 4- to 12-membered heterocyclyl, C6-10 aryl, 5- to 12-membered heteroaryl, (4- to 12-membered heterocyclyl)(C1-8 heteroalkyl), (C6-10 aryl)(C1-8 heteroalkyl), (5- to 12-membered heteroaryl)(C1-8 heteroalkyl), —N(R5a)2, —C(O)R5b, —C(O)OR5a, —C(O)N(R5a)2, —NR5aC(O)R5b,
—NR5aC(O)N(R5a)2, —NR5aC(O)OR5a, —OC(O)N(R5a)2, —OC(O)OR5a, —SR5a, —S(O)R5b, —S(O)2R5b,
—S(O)3R5a, —S(O)N(R5a)2, —S(O)2N(R5a)2, —NR5aS(O)R5b, —NR5aS(O)2R5b, —NR5aS(O)N(R5a)2, or
—NR5aS(O)2N(R5a)2, each of which is optionally substituted with one to eight R5c, or two R5 are optionally taken together to form oxo;
each R5a is independently hydrogen, C1-8 alkyl, C1-8 haloalkyl, C3-10 cycloalkyl, or 4- to 12-membered heterocyclyl, and
each R5b is independently C1-8 alkyl, C1-8 haloalkyl, C3-10 cycloalkyl, 4- to 12-membered heterocyclyl, or 5- to 12-membered heteroaryl;
each R5c is independently halogen, cyano, C1-8 haloalkyl, C1-8 alkyl, C1-8 alkoxy, C1-8 haloalkoxy, (C1-8 alkoxy)(C1-8 alkoxy), hydroxyl, SR5d, N(R5d)2, N(R5d)2(C1-8 alkoxy), C3-10 cycloalkyl, and 4- to 12-membered heterocyclyl, or
two R5c are optionally taken together to form oxo;
each R5d is independently hydrogen, C1-8 alkyl, or C1-8 haloalkyl;
each R6 is halogen, —CN, —OH, C1-8 alkyl, C1-8 heteroalkyl, C3-8 cycloalkyl, C1-8 haloalkyl, C1-8 alkoxy, 4- to 12-membered heterocyclyl, C6-10 aryl, 5- to 12-membered heteroaryl, —N(R6a)2, —C(O)R6b, —C(O)N(R6a)2, or —C(O)OR6a, or
two R6 are taken together to form oxo;
each R6a is independently hydrogen, C1-8 alkyl, or C1-8 haloalkyl, or
two R6a on the same atom are optionally taken together to form 4- to 6-membered heterocyclyl;
each R6b is independently C1-8 alkyl or C1-8 haloalkyl;
each R7 is independently hydrogen, halogen, —CN, —N3, —NO2, —SF5, —SCF3, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 heteroalkyl, C3-8 cycloalkyl, C1-8 haloalkyl, 4- to 12-membered heterocyclyl, C6-10 aryl, 5- to 12-membered heteroaryl, —OR7a, —C(O)R7b, —N(R7a)2, —C(O)OR7a, —C(O)N(R7a)2, —NR7aC(O)R7b, —NR7aC(O)N(R7a)2, —NR7aC(O)OR7a, —OC(O)N(R7a)2, —OC(O)OR7a, —SR7a, —S(O)R7b, —S(O)2R7b, —S(O)3R7a, —S(O)N(R7a)2, —S(O)2N(R7a)2, —NR7aS(O)R7b, —NR7aS(O)2R7b, —NR7aS(O)N(R7a)2, or —NR7aS(O)2N(R7a)2, each of which is optionally and independently substituted with one to eight R8;
each R7a is independently hydrogen, C1-8 alkyl, C1-8 haloalkyl, C3-10 cycloalkyl, or 4- to 12-membered heterocyclyl, or
two R7a on the same atom are optionally taken together to form a 4- to 8-membered heterocyclyl optionally substituted by oxo, halo, or C1-6 alkyl, wherein said alkyl is optionally substituted with one to eight R8;
each R7b is independently C1-8 alkyl, C1-8 haloalkyl, C3-10 cycloalkyl, or 4- to 12-membered heterocyclyl;
each R8 is halogen, —CN, —OH, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 heteroalkyl, C3-8 cycloalkyl, C1-8 haloalkyl, C1-8 alkoxy, 4- to 12-membered heterocyclyl, C6-10 aryl, 5- to 12-membered heteroaryl, —N(R8a)2, —C(O)R8b, or —C(O)OR8a, or two R8 are optionally taken together to form oxo;
each R8a is independently hydrogen, C1-8 alkyl, or C1-8 haloalkyl;
each R8b is independently C1-8 alkyl or C1-8 haloalkyl;
and
Z is O.

53 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/684,340Filed 14 Nov 2019 · continuation
Priority: 17 May 2017
Published: US 2020/0087319 A119 Mar 2020
Granted: 21 Dec 2021
Term ends: Not estimatedThe source records don’t support an estimate.

Classification15 codes

C07D 498/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 11/00
Drugs for disorders of the respiratory system

Family

Application62/507,698Us provisional application · filed 17 May 2017
Application62/664,895Us provisional application · filed 30 Apr 2018
PCT/US2018/033266Parent of this continuation · filed 17 May 2018
US 2020/0087319 A1Pre-grant publication · published 19 Mar 2020
US 11,203,600 B2This patent

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

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Abstract

The present disclosure relates generally to compounds and compositions, intermediates, processes for their preparation, and their use as kinase inhibitors.

A compound according to Formula I:

or a pharmaceutically acceptable salt, isotopic analog, or isomer thereof, wherein
W1, W3, and W4 are CR7;
W2 is N;
R1a, R1b, and R1c are independently hydrogen, halogen, —CN, —N3, —NO2, —OH, —SF5, —SCF3, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 heteroalkyl, C3-8 cycloalkyl, C1-8 haloalkyl, C1-8 alkoxy, C1-8 haloalkoxy, 4- to 12-membered heterocyclyl, C6-10 aryl, 5- to 12-membered heteroaryl, —N(R1d)2, —C(O)R1e, —C(O)OR1d, —C(O)N(R1d)2, —NR1dC(O)R1e, —NR1dC(O)N(R1d)2, —NR1dC(O)OR1d, —OC(O)N(R1d)2, —OC(O)OR1d, —SR1d, —S(O)R1e, —S(O)2R1e, —S(O)3R1d, —S(O)N(R1d)2, —S(O)2N(R1d)2, —NR1dS(O)R1e, —NR1dS(O)2R1e, —NR1dS(O)N(R1d)2, or —NR1dS(O)2N(R1d)2, wherein each of R1a, R1b, and R1c is optionally and independently substituted with one to eight R5 and at least one of R1a, R1b, and R1c is other than hydrogen;
or
R1b and R1c are optionally taken together to form C3-10 cycloalkyl or 4- to 12-membered heterocyclyl, each of which is optionally substituted with one to eight R5;
or
R1a, R1b, and R1c are optionally taken together to form C5-10 cycloalkyl or 6- to 8-membered heterocyclyl, each of which is optionally substituted with one to eight R5;
each R1d is independently hydrogen, C1-8 alkyl, C1-8 haloalkyl, C3-10 cycloalkyl, or 4- to 12-membered heterocyclyl, or
two R1d on the same atom are optionally taken together to form a 4- to 8-membered heterocyclyl optionally substituted by oxo, halo, or C1-6 alkyl, wherein said alkyl is optionally substituted with one to eight R5;
each R1e is independently C1-8 alkyl, C1-8 haloalkyl, C3-10 cycloalkyl, or 4- to 12-membered heterocyclyl;
R2a and R2b are independently hydrogen, halogen, C1-8 alkyl, C1-8 haloalkyl, C2-8 alkenyl, or C2-8 alkynyl, or
R2a and R2b are optionally taken together to form C3-6 cycloalkyl or 4- to 6-membered heterocyclyl, each of which is optionally substituted with one to eight R6;
R3a and R3b are independently hydrogen, halogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 haloalkyl, C3-6 cycloalkyl, or 4- to 6-membered heterocyclyl, wherein said cycloalkyl and said heterocyclyl are optionally substituted with one to eight R6, or
R3a and R3b are optionally taken together to form oxo, C3-6 cycloalkyl, or 4- to 6-membered heterocyclyl, wherein said cycloalkyl and said heterocyclyl are optionally substituted with one to eight R6;
Y is CR4aR4b;
R4a and R4b are independently hydrogen, halogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 haloalkyl, C3-6 cycloalkyl, or 4- to 6-membered heterocyclyl, wherein said cycloalkyl and said heterocyclyl are optionally substituted with one to eight R6, or
R4a and R4b are optionally taken together to form C3-6 cycloalkyl or 4- to 6-membered heterocyclyl, wherein said cycloalkyl and said heterocyclyl are optionally substituted with one to eight R6, or
R4a and R1b are optionally taken together to form 4- to 12-membered heterocyclyl, which is optionally substituted with one to eight R6, or
R4a and R3a are optionally taken together to form C3-8 cycloalkyl or 4- to 12-membered heterocyclyl, each of which is optionally substituted with one to eight R6,
each R5 is independently halogen, —CN, —OH, —SF5, —SCF3, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 heteroalkyl, C3-8 cycloalkyl, C1-8 alkoxy, 4- to 12-membered heterocyclyl, C6-10 aryl, 5- to 12-membered heteroaryl, (4- to 12-membered heterocyclyl)(C1-8 heteroalkyl), (C6-10 aryl)(C1-8 heteroalkyl), (5- to 12-membered heteroaryl)(C1-8 heteroalkyl), —N(R5a)2, —C(O)R5b, —C(O)OR5a, —C(O)N(R5a)2, —NR5aC(O)R5b, —NR5aC(O)N(R5a)2, —NR5aC(O)OR5a, —OC(O)N(R5a)2, —OC(O)OR5a, —SR5a, —S(O)R5b, —S(O)2R5b, —S(O)3R5a, —S(O)N(R5a)2, —S(O)2N(R5a)2, —NR5aS(O)R5b, —NR5aS(O)2R5b, —NR5aS(O)N(R5a)2, or —NR5aS(O)2N(R5a)2, each of which is optionally substituted with one to eight R5c, or
two R5 are optionally taken together to form oxo;
each R5a is independently hydrogen, C1-8 alkyl, C1-8 haloalkyl, C3-10 cycloalkyl, or 4- to 12-membered heterocyclyl, and
each R5b is independently C1-8 alkyl, C1-8 haloalkyl, C3-10 cycloalkyl, 4- to 12-membered heterocyclyl, or 5- to 12-membered heteroaryl;
each R5c is independently halogen, cyano, C1-8 haloalkyl, C1-8 alkyl, C1-8 alkoxy, C1-8 haloalkoxy, (C1-8 alkoxy)(C1-8 alkoxy), hydroxyl, SR5d, N(R5d)2, N(R5d)2(C1-8 alkoxy), C3-10 cycloalkyl, or 4- to 12-membered heterocyclyl, or
two R5c are optionally taken together to form oxo;
each R5d is independently hydrogen, C1-8 alkyl, or C1-8 haloalkyl;
each R6 is halogen, —CN, —OH, C1-8 alkyl, C1-8 heteroalkyl, C3-8 cycloalkyl, C1-8 haloalkyl, C1-8 alkoxy, 4- to 12-membered heterocyclyl, C6-10 aryl, 5- to 12-membered heteroaryl, —N(R6a)2, —C(O)R6b, —C(O)N(R6a)2, or —C(O)OR6a, or
two R6 are taken together to form oxo;
each R6a is independently hydrogen, C1-8 alkyl, or C1-8 haloalkyl, or
two R6a on the same atom are optionally taken together to form 4- to 6-membered heterocyclyl;
each R6b is independently C1-8 alkyl or C1-8 haloalkyl;
each R7 is independently hydrogen, halogen, —CN, —N3, —NO2, —SF5, —SCF3, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 heteroalkyl, C3-8 cycloalkyl, C1-8 haloalkyl, 4- to 12-membered heterocyclyl, C6-10 aryl, 5- to 12-membered heteroaryl, —OR7a, —C(O)R7b, —N(R7a)2, —C(O)OR7a, —C(O)N(R7a)2, —NR7aC(O)R7b, —NR7aC(O)N(R7a)2, —NR7aC(O)OR7a, —OC(O)N(R7a)2, —OC(O)OR7a, —SR7a, —S(O)R7b, —S(O)2R7b, —S(O)3R7a, —S(O)N(R7a)2, —S(O)2N(R7a)2, —NR7aS(O)R7b, —NR7aS(O)2R7b, —NR7aS(O)N(R7a)2, or —NR7aS(O)2N(R7a)2, each of which is optionally and independently substituted with one to eight R8;
each R7a is independently hydrogen, C1-8 alkyl, C1-8 haloalkyl, C3-10 cycloalkyl, or 4- to 12-membered heterocyclyl, or
two R7a on the same atom are optionally taken together to form a 4- to 8-membered heterocyclyl optionally substituted by oxo, halo, or C1-6 alkyl, wherein said alkyl is optionally substituted with one to eight R8;
each R7b is independently C1-8 alkyl, C1-8 haloalkyl, C3-10 cycloalkyl, or 4- to 12-membered heterocyclyl;
each R8 is halogen, —CN, —OH, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 heteroalkyl, C3-8 cycloalkyl, C1-8 haloalkyl, C1-8 alkoxy, 4- to 12-membered heterocyclyl, C6-10 aryl, 5- to 12-membered heteroaryl, —N(R8a)2, —C(O)R8b, or —C(O)OR8a, or
two R8 are optionally taken together to form oxo;
each R8a is independently hydrogen, C1-8 alkyl, or C1-8 haloalkyl;
each R8b is independently C1-8 alkyl or C1-8 haloalkyl;
and
Z is O.

39 more elements

Facts

Application

16/684,340Filed 14 Nov 2019 · continuation

Priority

17 May 2017

Published

US 2020/0087319 A119 Mar 2020

Granted

21 Dec 2021

Term ends

Not estimatedThe source records don’t support an estimate.

Classification15 codes

C07D 498/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 11/00
Drugs for disorders of the respiratory system

Family

Application62/507,698Us provisional application · filed 17 May 2017

Application62/664,895Us provisional application · filed 30 Apr 2018

PCT/US2018/033266Parent of this continuation · filed 17 May 2018

US 2020/0087319 A1Pre-grant publication · published 19 Mar 2020

US 11,203,600 B2This patent

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