US 9,868,749 B2Granted

Fused imidazole and pyrazole derivatives as modulators of TNF activity

AssigneeUcb Biopharma Sprl

InventorsRikki Peter Alexander, Jonathan Mark Bentley, Gareth Neil Brace, Daniel Christopher Brookings, Prafulkumar Tulshibhai Chovatia, Hervé Jean Claude Deboves, Craig Johnstone, Elizabeth Pearl Jones, Boris Kroeplien, Fabien Claude Lecomte, James Madden, Craig Miller, John Robert Porter, Matthew Duncan Selby, Michael Alan Shaw, Darshan Gunvant Vaidya, Ian Andrew Yule

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Abstract

A series of substituted benzimidazole, imidazo[1,2-a]pyridine and pyrazolo[1,5-a]pyridine derivatives, and analogues thereof, being potent modulators of human TNFα activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.

Claims7

Dependent claims

A compound represented by formula (IIB-A), (IIB-B) or (IIB-C), or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof:

wherein
V represents C—R22 or N;
R21 represents hydroxy(C1-6)alkyl, C1-6 alkylsulphonyl, (C1-6)alkyl-sulphoximinyl or [(C1-6)alkyl][N—(C1-6)alkyl]sulphoximinyl;
or R21 represents (C3-7)-cycloalkyl, (C3-7)heterocycloalkyl, (C4-9)heterobicycloalkyl or (C4-9)spiroheterocycloalkyl, any of which groups may be optionally substituted by one, two or three substituents independently selected from halogen, C1-6 alkyl, trifluoromethyl, hydroxy, oxo, amino, carboxy and C2-6 alkoxycarbonyl,
R22 represents hydrogen, halogen or C1-6 alkyl;
R23 represents hydrogen, C1-6 alkyl, trifluoromethyl or C1-6 alkoxy;
A represents C—R2 or N;
D represents C—R4 or N;
E represents —CH2— or —CH(CH3)—;
Y represents a group of formula
(Ya-1), (Ya-2), (Ya-3), (Yb-1), (Yb-2), (Yb-3), (Yb-4), (Yb-5), (Yb-6), (Yb-7), (Yc-1) or (Yd-1):
wherein
the asterisk (*) represents the point of attachment to the remainder of the molecule;
R1g represents hydrogen, halogen, cyano, C1-6 alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxy, hydroxy(C1-6)alkyl, C1-6 alkoxy, difluoromethoxy, trifluoro-methoxy, pentafluorothio, C1-6 alkylthio, C1-6 alkylsulphinyl, C1-6 alkylsulphonyl, amino, amino(C1-6)alkyl, C1-6 alkylamino, di(C1-6)alkylamino, formyl, C2-6 alkylcarbonyl, carboxy, C2-6 alkoxycarbonyl, aminocarbonyl, C1-6 alkylaminocarbonyl, di(C1-6)alkyl-aminocarbonyl, hydroxy(C1-6)alkylaminocarbonyl, (C1-6)alkoxy(C1-6)alkylaminocarbonyl, (C3-7)cycloalkylaminocarbonyl, heteroaryl(C1-6)alkylaminocarbonyl, aminosulphonyl, C1-6 alkylaminosulphonyl, di(C1-6)alkylaminosulphonyl, (C1-6)alkylsulphoximinyl, [(C1-6)alkyl][N—(C1-6)alkyl]sulphoximinyl, hydroxy(C3-7)heterocycloalkyl, (C1-6)alkoxy-(C3-7)heterocycloalkyl, (C3-7)heterocycloalkylcarbonyl, hydroxy(C3-7)heterocycloalkyl-carbonyl, oxo(C3-7)heterocycloalkylcarbonyl, (C1-6)alkylsulphonyl(C3-7)heterocycloalkyl-carbonyl or (C2-6)alkoxycarbonyl(C3-7)heterocycloalkylcarbonyl;
R2g and R3g independently represent hydrogen or halogen;
R2 represents hydrogen or halogen;
R4 represents hydrogen;
R5 represents C1-6 alkyl, optionally substituted by halogen, hydroxy or C1-6 alkoxy;
R7a and R7b independently represent hydrogen or C1-6 alkyl;
R8a and R8b independently represent hydrogen, halogen or C1-6 alkyl;
or
R8a and R8b, when taken together with the carbon atom to which they are both attached, represent cyclopropyl;
and
R9a and R9b independently represent hydrogen or C1-6 alkyl.

21 more elements

A compound which is

4-{[6-(6-Methanesulfonylpyridin-3-yl)-2-methylimidazo[1,2-a]pyridin-3-yl]methyl}-2H,3H,4H-pyrido[3,2-b][1,4]oxazin-3-one;
8-Fluoro-4-({6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]-pyridin-3-yl}methyl)-3,4-dihydro-2H-1,4-benzoxazin-3-one;
7-Fluoro-3-({6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]-pyridin-3-yl}methyl)-2,3-dihydro-1,3-benzoxazol-2-one;
3-({6-[2-(2-Hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}methyl)-2H,3H-[1,3]oxazolo[4,5-d]pyrimidin-2-one;
8-Fluoro-4-{[6-(6-methanesulfonylpyridin-3-yl)-2-methylimidazo[1,2-a]pyridin-3-yl]-methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one;
tert-Butyl 4-(5-{3-[(8-Fluoro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-4-yl)methyl]-2-methylimidazo[1,2-a]pyridin-6-yl}pyrimidin-2-yl)piperazine-1-carboxylate;
8-Fluoro-4-({2-methyl-6-[2-(morpholin-4-yl)pyrimidin-5-yl]imidazo[1,2-a]pyridin-3-yl}methyl)-3,4-dihydro-2H-1,4-benzoxazin-3-one;
8-Fluoro-4-({2-methyl-6-[2-(piperazin-1-yl)pyrimidin-5-yl]imidazo[1,2-a]pyridin-3-yl}-methyl)-3,4-dihydro-2H-1,4-benzoxazin-3-one hydrochloride;
(2R)-8-Fluoro-4-({6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]-pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
Ethyl 1-(5-{3-[(8-Fluoro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-4-yl)methyl]-2-methyl-imidazo[1,2-a]pyridin-6-yl}pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate;
8-Fluoro-4-({6-[6-(2-hydroxypropan-2-yl)pyridin-3-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}methyl)-3,4-dihydro-2H-1,4-benzoxazin-3-one;
8-Fluoro-4-({2-methyl-6-[2-(3-oxopiperazin-1-yl)pyrimidin-5-yl]imidazo[1,2-a]pyridin-3-yl}methyl)-3,4-dihydro-2H-1,4-benzoxazin-3-one;
1-(5-{3-[(8-Fluoro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-4-yl)methyl]-2-methylimidazo-[1,2-a]pyridin-6-yl}pyridin-2-yl)-4-methylpiperidine-4-carboxylic acid;
(2R)-8-Fluoro-2-methyl-4-({2-methyl-6-[2-(3-oxopiperazin-1-yl)pyrimidin-5-yl]imidazo-[1,2-a]pyridin-3-yl}methyl)-3,4-dihydro-2H-1,4-benzoxazin-3-one;
8-Fluoro-4-({2-methyl-6-[6-(piperazin-1-yl)pyridin-3-yl]imidazo[1,2-a]pyridin-3-yl}-methyl)-3,4-dihydro-2H-1,4-benzoxazin-3-one;
Methyl (1S,5R)-3-(5-{3-[(8-fluoro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-4-yl)methyl]-2-methylimidazo[1,2-a]pyridin-6-yl}pyrimidin-2-yl)-3-azabicyclo[3.2.1]octane-8-carboxylate;
(1r,4r)-4-(5-{3-[(8-Fluoro-3-oxo-1,4-benzoxazin-4-yl)methyl]-2-methylimidazo[1,2-a]-pyridin-6-yl}pyrimidin-2-yl)cyclohexanecarboxylic acid;
(2R)-8-Fluoro-4-({7-fluoro-6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-6,8-Fluoro-4-({7-fluoro-6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
4-(5-{3-[(8-Fluoro-2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-4-yl)methyl]-2-methylimidazo[1,2-a]pyridin-6-yl}pyrimidin-2-yl)cyclohexane-1-carboxylic acid;
(2R)-6,8-Difluoro-4-({7-fluoro-6-[2-(3-hydroxyoxetan-3-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({7-fluoro-2-methyl-6-[2-(3-oxopiperazin-1-yl)pyrimidin-5-yl]imidazo-[1,2-a]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({7-fluoro-6-[2-(3-hydroxyoxetan-3-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-6,8-Difluoro-4-({7-fluoro-6-[2-(3-hydroxyazetidin-3-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-6,8-Difluoro-4-({7-fluoro-6-[2-(4-hydroxytetrahydropyran-4-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxycyclobutyl)pyrimidin-5-yl]-2-methylimidazo-[1,2-a]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-(1-{7-fluoro-6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyridin-3-yl}ethyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
8-Fluoro-4-({7-fluoro-6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}methyl)-2,2-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({7-fluoro-6-[2-(3-hydroxy-1-methylazetidin-3-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one formic acid salt;
(7R)-5-({6-[2-(2-Hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyrazin-3-yl}methyl)-7-methyl-5H,6H,7H-pyrimido[4,5-b][1,4]oxazin-6-one;
(2R)-6,8-Difluoro-4-({6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyrazin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({6-[2-(3-hydroxyoxetan-3-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]-pyrazin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
8-Fluoro-4-({6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyrazin-3-yl}methyl)-2,2-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({6-[2-(4-hydroxytetrahydropyran-4-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyrazin-3-yl}methyl)-2-methyl-1,4-benzoxazin-3-one;
(2R)-4-({6-[2-(1,1-Difluoroethyl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyrazin-3-yl}methyl)-8-fluoro-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-6,8-Difluoro-4-({7-fluoro-2-methyl-6-[2-(3-oxopiperazin-1-yl)pyrimidin-5-yl]-imidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
4-({6-[2-(2-Hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyrazin-3-yl}-methyl)-2H,3H,4H-pyrido[4,3-b][1,4]oxazin-3-one;
4-({7-Fluoro-6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]-pyridin-3-yl}methyl)-2H,3H,4H-pyrido[3,2-b][1,4]oxazin-3-one;
4-({6-[2-(2-Hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyrazin-3-yl}-methyl)-2H,3H,4H-pyrido[3,2-b][1,4]oxazin-3-one;
6,8-Difluoro-4-[(7-fluoro-6-{2-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl}-2-methylimidazo[1,2-a]pyridin-3-yl)methyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-6,8-Difluoro-2-methyl-4-({2-methyl-6-[2-(5-oxo-1,4-diazepan-1-yl)pyrimidin-5-yl]-imidazo[1,2-a]pyrazin-3-yl}methyl)-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-4-{[6-(2-{3,7-Dioxa-9-azabicyclo[3.3.1]nonan-9-yl}pyrimidin-5-yl)-7-fluoro-2-methylimidazo[1,2-a]pyridin-3-yl]methyl}-8-fluoro-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
6,8-Difluoro-4-[(7-fluoro-6-{2-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl}-2-methylimidazo[1,2-a]pyridin-3-yl)methyl]-2,2-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-6,8-Difluoro-4-[(6-{2-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl}-2-methylimidazo[1,2-a]pyrazin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2S)-6,8-Difluoro-4-[(6-{2-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl}-2-methylimidazo[1,2-a]pyrazin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-6,8-Difluoro-4-({7-fluoro-6-[2-(3-fluorooxetan-3-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
6,8-Difluoro-4-({6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]-pyrazin-3-yl}methyl)-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-6,8-Difluoro-2-methyl-4-({2-methyl-6-[2-(3-oxopiperazin-1-yl)pyrimidin-5-yl]-imidazo[1,2-a]pyrazin-3-yl}methyl)-3,4-dihydro-2H-1,4-benzoxazin-3-one;
6,8-Difluoro-4-({6-[2-(3-hydroxy-3-methylazetidin-1-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyrazin-3-yl}methyl)-2,2-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-6,8-Difluoro-4-({6-[2-(3-fluorooxetan-3-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]-pyrazin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2S)-6,8-Difluoro-4-({7-fluoro-6-[2-(3-hydroxy-3-methylazetidin-1-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-6,8-Difluoro-4-[(7-fluoro-6-{2-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]-pyrimidin-5-yl}-2-methylimidazo[1,2-a]pyridin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
7-Fluoro-3-({7-fluoro-6-[2-(3-hydroxy-3-methylazetidin-1-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyridin-3-yl}methyl)-2,3-dihydro-1,3-benzoxazol-2-one formate;
(2R)-6,8-Difluoro-2-methyl-4-({2-methyl-6-[2-(morpholin-4-yl)pyrimidin-5-yl]imidazo-[1,2-a]pyrazin-3-yl}methyl)-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-6,8-Difluoro-4-({6-[2-(3-hydroxy-3-methylazetidin-1-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyrazin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
6,8-Difluoro-4-({7-fluoro-6-[2-(3-hydroxy-3-methylazetidin-1-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}methyl)-2,2-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({7-fluoro-6-[2-(3-hydroxy-3-methylazetidin-1-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
6,8-Difluoro-4-({7-fluoro-6-[2-(3-hydroxy-3-methylazetidin-1-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}methyl)-3,4-dihydro-2H-1,4-benzoxazin-3-one;
2,2,6,8-Tetrafluoro-4-({7-fluoro-6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyridin-3-yl}methyl)-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2S)-6,8-Difluoro-4-({6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyrazin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
2,2,6,8-Tetrafluoro-4-({7-fluoro-6-[2-(3-hydroxy-3-methylazetidin-1-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}methyl)-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2S)-6,8-Difluoro-4-[(7-fluoro-6-{2-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]-pyrimidin-5-yl}-2-methylimidazo[1,2-a]pyridin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-6,8-Difluoro-4-({7-fluoro-2-methyl-6-[2-(morpholin-4-yl)pyrimidin-5-yl]imidazo-[1,2-a]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
6,8-Difluoro-4-[(6-{2-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl}-2-methylimidazo[1,2-a]pyrazin-3-yl)methyl]-2,2-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
7-Fluoro-3-({7-fluoro-6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}methyl)-2,3-dihydro-1,3-benzoxazol-2-one;
(2R)-6,8-Difluoro-4-({7-fluoro-2-methyl-6-[2-(3-oxopiperazin-1-yl)pyrimidin-5-yl]-imidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
2,2,6,8-Tetrafluoro-4-[(7-fluoro-6-{2-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]-pyrimidin-5-yl}-2-methylimidazo[1,2-a]pyridin-3-yl)methyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-4-({6-[2-(2-Hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyrazin-3-yl}methyl)-2-methyl-2H,3H,4H-pyrido[3,2-b][1,4]oxazin-3-one;
4-({7-Fluoro-6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]-pyridin-3-yl}methyl)-2H,3H,4H-pyrido[4,3-b][1,4]oxazin-3-one;
(2R)-6,8-Difluoro-4-({7-fluoro-6-[2-(3-hydroxy-3-methylazetidin-1-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-[(7-fluoro-6-{2-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl}-2-methylimidazo[1,2-a]pyridin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
6,8-Difluoro-4-({7-fluoro-6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo-[1,2-a]pyridin-3-yl}methyl)-2,2-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-4-({6-[2-(3,7-Dioxa-9-azabicyclo[3.3.1]nonan-9-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyrazin-3-yl}methyl)-6,8-difluoro-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-6,8-Difluoro-4-({7-fluoro-2-methyl-6-[2-(5-oxo-1,4-diazepan-1-yl)pyrimidin-5-yl]-imidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxycyclopropyl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
4-({6-[2-(3,3-Difluoro-1-hydroxycyclobutyl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]-pyrazin-3-yl}methyl)-6,8-difluoro-2,2-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-4-({7-Fluoro-6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]-pyridin-3-yl}methyl)-2-methyl-2H,3H,4H-pyrido[3,2-b][1,4]oxazin-3-one;
4-({7-Fluoro-6-[2-(1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]-pyridin-3-yl}methyl)spiro[1,4-benzoxazine-2,1′-cyclopropane]-3-one;
Methyl (2R)-8-fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-3-oxo-1,4-benzoxazine-6-carboxylate;
(2R)-7,8-Difluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methyl-imidazo[1,2a-]pyridin-3-yl}methyl)-2-methyl-1,4-benzoxazin-3-one;
8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methylimidazo-[1,2a-]pyridin-3-yl}methyl)spiro[1,4-benzoxazine-2,1′-cyclopropane]-3-one;
-8-Fluoro-4-({7-fluoro-6-[2-(3-hydroxy-3-methylazetidin-1-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2a-]pyridin-3-yl}methyl)spiro[1,4-benzoxazine-2,1′-cyclopropane]-3-one;
8-Fluoro-4-[(7-fluoro-6-{2-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl}-2-methylimidazo[1,2-a]pyridin-3-yl)methyl]spiro[1,4-benzoxazine-2,1′-cyclopropane]-3-one;
(2R)-5,6,8-Trifluoro-4-[(6-{2-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl}-2-methylimidazo[1,2-a]pyrazin-3-yl)methyl]-2-methyl-1,4-benzoxazin-3-one;
2-(5-{7-Fluoro-3-[(8-fluoro-3-methyl-2,3-dihydro-1,4-benzoxazin-4-yl)methyl]-2-methylimidazo[1,2a-]pyridin-6-yl}pyrimidin-2-yl)propan-2-ol;
(2R)-8-Chloro-6-fluoro-4-({6-[2-(3-hydroxy-3-methylazetidin-1-yl)pyrimidin-5-yl]-2-methylimidazo[1,2a-]pyrazin-3-yl}methyl)-2-methyl-1,4-benzoxazin-3-one;
(2R)-8-Chloro-4-({6-[2-(3-hydroxy-3-methylazetidin-1-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyrazin-3-yl}methyl)-2-methyl-1,4-benzoxazin-3-one;
(2S)-8-Fluoro-4-({6-[2-(1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyrazin-3-yl}methyl)-2-methyl-1,4-benzoxazin-3-one;
(2S)-8-Fluoro-4-[(7-fluoro-6-{2-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl}-2-methylimidazo[1,2-a]pyridin-3-yl)methyl]-2-methyl-1,4-benzoxazin-3-one;
(2S)-8-Fluoro-4-({7-fluoro-6-[2-(3-hydroxy-3-methylazetidin-1-yl)pyrimidin-5-yl]-2-methylimidazo[1,2a-]pyridin-3-yl}methyl)-2-methyl-1,4-benzoxazin-3-one;
(2R)-4-({7-Fluoro-6-[2-(1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methylimidazo[1,2a-]pyridin-3-yl}methyl)-2-methyl-8-(trifluoromethyl)pyrido[3,2-b][1,4]oxazin-3-one;
(2R)-4-({6-[2-(1-Hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methylimidazo[1,2a-]-pyrazin-3-yl}methyl)-2-methyl-8-(trifluoromethyl)pyrido[3,2-b][1,4]oxazin-3-one;
(2R)-8-Fluoro-4-({6-[2-(1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyrazin-3-yl}methyl)-2-methyl-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methyl-imidazo[1,2a-]pyridin-3-yl}methyl)-2-methyl-3-oxo-1,4-benzoxazine-6-carbonitrile;
(2S)-8-Fluoro-4-({7-fluoro-6-[6-(1-hydroxy-1-methylethyl)pyridin-3-yl]-2-methyl-imidazo[1,2a-]pyridin-3-yl}methyl)-2-methyl-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({6-[2-(1-hydroxycyclobutyl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]-pyrazin-3-yl}methyl)-2-methyl-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-[(6-{2-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl}-2-methylimidazo[1,2-a]pyrazin-3-yl)methyl]-2-methyl-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-2-methyl-4-({2-methyl-6-[2-(morpholin-4-yl)pyrimidin-5-yl]imidazo[1,2a-]pyrazin-3-yl}methyl)-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({6-[2-(3-hydroxy-3-methylazetidin-1-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyrazin-3-yl}methyl)-2-methyl-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({6-[6-(1-hydroxy-1-methylethyl)pyridin-3-yl]-2-methylimidazo[1,2a-]-pyrazin-3-yl}methyl)-2-methyl-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-2-methyl-4-({2-methyl-6-[2-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)-pyrimidin-5-yl]imidazo[1,2a-]pyrazin-3-yl}methyl)-1,4-benzoxazin-3-one;
8-Fluoro-4-[(6-{2-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl}-2-methyl-imidazo[1,2-a]pyrazin-3-yl)methyl]-1,4-benzoxazin-3-one;
(2R)-6-Bromo-8-fluoro-4-({6-[2- (1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methyl-imidazo[1,2a-]pyrazin-3-yl}methyl)-2-methyl-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-2-methyl-4-{[2-methyl-6-(6-methylsulfonylpyridin-3-yl)imidazo[1,2-a]-pyrazin-3-yl]methyl}-1,4-benzoxazin-3-one;
(2R)-4-({6-[2-(6,6-Dioxo-λ6-thia-2-azaspiro[3.3]heptan-2-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyrazin-3-yl}methyl)-8-fluoro-2-methyl-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-2-methyl-4-({2-methyl-6-[2-(3-oxa-6-azaspiro[3.3]heptan-6-yl)pyrimidin-5-yl]imidazo[1,2a-]pyrazin-3-yl}methyl)-1,4-benzoxazin-3-one;
(2R)-7,8-Difluoro-4-[(6-{2-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl}-2-methylimidazo[1,2a-]pyrazin-3-yl)methyl]-2-methyl-1,4-benzoxazin-3-one;
4-({6-[2-(1-Hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methylimidazo[1,2a-]pyrazin-3-yl}methyl)spiro[1,4-benzoxazine-2,1′-cyclopropane]-3-one;
8-Fluoro-4-({6-[2-(1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]-pyrazin-3-yl}methyl)spiro[1,4-benzoxazine-2,1′-cyclopropane]-3-one;
(2R)-8-Fluoro-2-methyl-4-({2-methyl-6-[2-(3-oxopiperazin-1-yl)pyrimidin-5-yl]imidazo-[1,2a-]pyrazin-3-yl}methyl)-1,4-benzoxazin-3-one;
(2R)-4-({6-[2-(3,3-Difluoroazetidin-1-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyrazin-3-yl}methyl)-8-fluoro-2-methyl-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({7-fluoro-2-(hydroxymethyl)-6-[2-(1-hydroxy-1-methylethyl)-pyrimidin-5-yl]imidazo[1,2a-]pyridin-3-yl}methyl)-2-methyl-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({6-[2-(1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methylimidazo[1,2-b]pyridazin-3-yl}methyl)-2-methyl-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-2-methyl-4-({2-methyl-6-[2-(5-oxo-1,4-diazepan-1-yl)pyrimidin-5-yl]-imidazo[1,2-a]pyrazin-3-yl}methyl)-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methyl-imidazo[1,2a-]pyridin-3-yl}methyl)-2-methyl-3-oxo-1,4-benzoxazine-6-carboxylic acid;
(2R)-8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methyl-imidazo[1,2a-]pyridin-3-yl}methyl)-N,2-dimethyl-3-oxo-1,4-benzoxazine-6-carboxamide;
(2S)-6,8-Difluoro-4-({7-fluoro-6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2a-]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2S)-8-Fluoro-4-({7-fluoro-6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methyl-imidazo[1,2a-]pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methyl-imidazo[1,2a-]pyridin-3-yl}methyl)-6-(1-hydroxy-1-methylethyl)-2-methyl-1,4-benzoxazin-3-one;
8-Fluoro-4-({6-[6-(methanesulfonyl)pyridin-3-yl]-2-methylimidazo[1,2a-]pyridin-3-yl}-methyl)-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-[(7-fluoro-6-{6-[imino(methyl)oxo-λ6-sulfanyl]pyridin-3-yl}-2-methylimidazo[1,2-a]-pyridin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2S)-8-Fluoro-4-[(7-fluoro-6-{6-[imino(methyl)oxo-λ6-sulfanyl]pyridin-3-yl}-2-methyl-imidazo[1,2a-]pyridin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
8-Fluoro-4-[(7-fluoro-6-{6-[imino(methyl)oxo-λ6-sulfanyl]pyridin-3-yl}-2-methylimidazo[1,2-a]pyridin-3-yl)methyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one;
8-Fluoro-4-[(7-fluoro-6-{6-[imino(methyl)oxo-λ6-sulfanyl]-4-methylpyridin-3-yl}-2-methylimidazo[1,2a-]pyridin-3-yl)methyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2S)-8-Fluoro-4-[(7-fluoro-6-{6-[imino(methyl)oxo-λ6-sulfanyl]-4-methylpyridin-3-yl}-2-methylimidazo[1,2a-]pyridin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-[(7-fluoro-2-methyl-6-{6-[methyl-(methylimino)oxo-λ6-sulfanyl]pyridin-3-yl}imidazo-[1,2-a]pyridin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-[(7-fluoro-6-{6-[imino(methyl)oxo-λ6-sulfanyl]-4-methylpyridin-3-yl}-2-methylimidazo-[1,2a-]pyridin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2S)-4-[(6-{6-[Ethyl(imino)oxo-λ6-sulfanyl]pyridin-3-yl}-7-fluoro-2-methylimidazo[1,2a-]pyridin-3-yl)-methyl]-8-fluoro-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-4-[(6-{6-[Ethyl(imino)oxo-λ6-sulfanyl]pyridin-3-yl}-7-fluoro-2-methylimidazo[1,2a-]pyridin-3-yl)-methyl]-8-fluoro-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Chloro-4-[(7-fluoro-6-{6-[imino(methyl)oxo-λ6-sulfanyl]pyridin-3-yl}-2-methylimidazo[1,2-a]-pyridin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-[(7-fluoro-6-{6-[imino(methyl)oxo-λ6-sulfanyl]-4-methylpyridin-3-yl}-2-methylimidazo-[1,2-a]pyridin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one, maleic acid salt;
(2R)-4-[(6-{6-[Ethyl(imino)oxo-λ6-sulfanyl]pyridin-3-yl}-7-fluoro-2-methylimidazo[1,2-a]pyridin-3-yl)-methyl]-8-fluoro-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one, maleic acid salt;
(2R)-8-Fluoro-4-[(6-{6-[imino(methyl)oxo-λ6-sulfanyl]pyridin-3-yl}-2-methylimidazo[1,2-a]pyridin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one, maleic acid salt;
5-Fluoro-1-[(7-fluoro-6-{6-[imino(methyl)oxo-λ6-sulfanyl]pyridin-3-yl}-2-methylimidazo[1,2-a]pyridin-3-yl)methyl]-3-methyl-1,2,3,4-tetrahydroquinolin-2-one;
(2S)-8-Fluoro-4-[(7-fluoro-2-methyl-6-{2-[(1s,3r)-1,3-dihydroxy-3-methylcyclobutyl]pyrimidin-5-yl}-imidazo[1,2-a]pyridin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2S)-8-Fluoro-4-[(7-fluoro-2-methyl-6-{2-[(1s,3s)-1,3-dihydroxycyclobutyl]pyrimidin-5-yl}imidazo[1,2-a]-pyridin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
8-Fluoro-4-[(7-fluoro-2-methyl-6-{2-[(1r,3s)-1,3-dihydroxy-3-methylcyclobutyl]pyrimidin-5-yl}-imidazo[1,2-a]pyridin-3-yl)methyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-[(7-fluoro-2-methyl-6-{2-[(1r,3s)-1,3-dihydroxy-3-methylcyclobutyl]pyrimidin-5-yl}-imidazo[1,2-a]pyridin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-6,8-Difluoro-2-methyl-4-[(2-methyl-6-{2-[(1r,3s)-1,3-dihydroxy-3-methylcyclobutyl]pyrimidin-5-yl}imidazo[1,2-a]pyrazin-3-yl)methyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2S)-8-Fluoro-4-[(7-fluoro-2-methyl-6-{2-[(1s,3s)-3-amino-1-hydroxycyclobutyl]pyrimidin-5-yl}imidazo-[1,2-a]pyridin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
8-Fluoro-4-[(7-fluoro-2-methyl-6-{6-[(1r,3s)-1,3-dihydroxy-3-methylcyclobutyl]pyridin-3-yl}imidazo-[1,2-a]pyridin-3-yl)methyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-[(7-fluoro-2-methyl-6-{6-[(1r,3s)-1,3-dihydroxy-3-methylcyclobutyl]pyridin-3-yl}imidazo-[1,2-a]pyridin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
8-Fluoro-4-[(7-fluoro-2-methyl-6-{2-[(1r,3s)-3-ethyl-1,3-dihydroxycyclobutyl]pyrimidin-5-yl}imidazo[1,2-a]pyridin-3-yl)methyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-4-{[6-(6-{[Dimethyl(oxo)-λ6-sulfanylidene]-amino}pyridin-3-yl)-7-fluoro-2-methylimidazo[1,2a-]-pyridin-3-yl]methyl}-8-fluoro-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-4-[(6-{6-[Ethyl(imino)oxo-λ6-sulfanyl]pyridin-3-yl}-2-methylimidazo[1,2-a]pyrazin-3-yl)methyl]-8-fluoro-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-2-methyl-4-[(2-methyl-6-{2-[(1r,3s)-3-ethyl-1,3-dihydroxycyclobutyl]pyrimidin-5-yl}-imidazo[1,2-a]pyrazin-3-yl)methyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-6-Bromo-8-chloro-4-({7-fluoro-6-[2-(2-hydroxy-propan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2a-]-pyridin-3-yl}methyl)-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
8-Fluoro-4-[(7-fluoro-6-{6-[imino(methyl)oxo-λ6-sulfanyl]pyridin-3-yl}-2-methylimidazo[1,2-a]pyridin-3-yl)methyl]-2,2-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-2-methyl-4-[(2-methyl-6-{2-[(1r,3s)-1,3-dihydroxy-3-methylcyclobutyl]pyrimidin-5-yl}-imidazo[1,2-a]pyrazin-3-yl)methyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-4-[(6-{6-[Cyclopropyl(imino)oxo-λ6-sulfanyl]-pyridin-3-yl}-7-fluoro-2-methylimidazo[1,2a-]pyridin-3-yl)methyl]-8-fluoro-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Chloro-2-methyl-4-[(2-methyl-6-{2-[(1r,3s)-1,3-dihydroxy-3-methylcyclobutyl]pyrimidin-5-yl}-imidazo[1,2-a]pyrazin-3-yl)methyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Chloro-4-[(7-fluoro-2-methyl-6-{2-[(1r,3s)-1,3-dihydroxy-3-methylcyclobutyl]pyrimidin-5-yl}-imidazo[1,2-a]pyridin-3-yl)methyl]-2-methyl-3,4-dihydro-2H-1,4-benzoxazin-3-one;
8-Chloro-4-[(2-methyl-6-{2-[(1r,3s)-1,3-dihydroxy-3-methylcyclobutyl]pyrimidin-5-yl}imidazo[1,2a-]-pyrazin-3-yl)methyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one;
8-Chloro-4-[(7-fluoro-2-methyl-6-{2-[(1r,3s)-1,3-dihydroxy-3-methylcyclobutyl]pyrimidin-5-yl}-imidazo[1,2a-]pyridin-3-yl)methyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-2-methyl-4-[(2-methyl-6-{2-[(1s,3r)-1-amino-3-hydroxy-3-methylcyclobutyl]pyrimidin-5-yl}-imidazo[1,2-a]pyrazin-3-yl)methyl]-3,4-dihydro-2H-1,4-benzoxazin-3-one;
8-Fluoro-4-({7-fluoro-6-[2-(2-hydroxypropan-2-yl)-pyrimidin-5-yl]-2-methylimidazo[1,2a-]pyridin-3-yl}-methyl)-2-methyl-3-oxo-N-(propan-2-yl)-3,4-dihydro-2H-1,4-benzoxazine-6-carboxamide;
(2S)-8-Fluoro-4-({7-fluoro-6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2a-]pyridin-3-yl}methyl)-2-methyl-3-oxo-N-(propan-2-yl)-3,4-dihydro-2H-1,4-benzoxazine-6-carboxamide;
(2R)-8-Fluoro-4-({7-fluoro-6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2a-]pyridin-3-yl}methyl)-2-methyl-3-oxo-N-(propan-2-yl)-3,4-dihydro-2H-1,4-benzoxazine-6-carboxamide;
8-Fluoro-4-({7-fluoro-6-[2-(2-hydroxypropan-2-yl)-pyrimidin-5-yl]-2-methylimidazo[1,2a-]pyridin-3-yl}-methyl)-N-(1-hydroxy-2-methylpropan-2-yl)-2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxamide;
8-Fluoro-4-({7-fluoro-6-[2-(2-hydroxypropan-2-yl)-pyrimidin-5-yl]-2-methylimidazo[1,2a-]pyridin-3-yl}-methyl)-N-(1-hydroxypropan-2-yl)-2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxamide;
N-Ethyl-8-fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methylimidazo[1,2a-]-pyridin-3-yl}methyl)-2-methyl-3-oxo-1,4-benzoxazine-6-carboxamide;
tert-Butyl 4-[8-fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methylimidazo[1,2a-]-pyridin-3-yl}methyl)-2-methyl-3-oxo-1,4-benzoxazine-6-carbonyl]piperazine-1-carboxylate;
8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)-pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}-methyl)-2-methyl-6-(piperazine-1-carbonyl)-1,4-benzoxazin-3-one;
8-Fluoro-4-({7-fluoro-6-[2-(2-hydroxypropan-2-yl)-pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}-methyl)-6-[(3-hydroxypyrrolidin-1-yl)carbonyl]-2-methyl-2H-1,4-benzoxazin-3(4H)-one;
8-Fluoro-4-({7-fluoro-6-[2-(2-hydroxypropan-2-yl)-pyrimidin-5-yl]-2-methylimidazo[1,2a-]pyridin-3-yl}-methyl)-N,N,2-trimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxamide;
N-Cyclopropyl-8-fluoro-4-({7-fluoro-6-[2-(2-hydroxy-propan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2a-]-pyridin-3-yl}methyl)-2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxamide;
8-Fluoro-4-({7-fluoro-6-[2-(2-hydroxypropan-2-yl)-pyrimidin-5-yl]-2-methylimidazo[1,2a-]pyridin-3-yl}-methyl)-N-(2-hydroxyethyl)-2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carboxamide;
8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)-pyrimidin-5-yl]-2-methylimidazo[1,2a-]pyridin-3-yl}-methyl)-N-(2-methoxyethyl)-2-methyl-3-oxo-1,4-benzoxazine-6-carboxamide;
8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)-pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}-methyl)-2-methyl-N-(oxazol-4-ylmethyl)-3-oxo-1,4-benzoxazine-6-carboxamide;
8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)-pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}-methyl)-2-methyl-6-[3-(methylsulfonyl)azetidine-1-carbonyl]-1,4-benzoxazin-3-one;
8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)-pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}-methyl)-2-methyl-6-(3-oxopiperazine-1-carbonyl)-1,4-benzoxazin-3-one;
8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)-pyrimidin-5-yl]-2-methylimidazo[1,2a-]pyridin-3-yl}-methyl)-2-methyl-3-oxo-1,4-benzoxazine-6-carboxamide;
(2R)-8-Fluoro-2-methyl-4-({2-methyl-6-[2-(2-methyl-5-oxo-1,4-diazepan-1-yl)pyrimidin-5-yl]imidazo[1,2a-]pyrazin-3-yl}methyl)-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-2-methyl-4-({2-methyl-6-[2-(7-methyl-5-oxo-1,4-diazepan-1-yl)pyrimidin-5-yl]imidazo[1,2a-]pyrazin-3-yl}methyl)-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-[(7-fluoro-2-methyl-6-{2-[(1R,5S)-6-oxa-3-azabicyclo[3.1.1]heptan-3-yl]pyrimidin-5-yl}-imidazo[1,2-a]pyridin-3-yl)methyl]-2-methyl-1,4-benzoxazin-3-one;
(2R)-6-Bromo-8-fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methylimidazo[1,2a-]pyridin-3-yl}methyl)-2-methyl-1,4-benzoxazin-3-one;
(2R)-8-Chloro-4-({7-fluoro-6-[2-(1-hydroxy-1-methyl-ethyl)pyrimidin-5-yl]-2-methylimidazo[1,2a-]pyridin-3-yl}methyl)-N-isopropyl-2-methyl-3-oxo-1,4-benzoxazine-6-carboxamide;
(2R)-8-Chloro-4-[(7-fluoro-6-{2-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]pyrimidin-5-yl}-2-methylimidazo[1,2-a]pyridin-3-yl)methyl]-N-isopropyl-2-methyl-3-oxo-1,4-benzoxazine-6-carboxamide;
8-Chloro-4-({7-fluoro-2-methyl-6-[2-(3-oxopiperazin-1-yl)pyrimidin-5-yl]imidazo[1,2a-]pyridin-3-yl}-methyl)-N-isopropyl-2-methyl-3-oxo-1,4-benzoxazine-6-carboxamide;
(2R)-8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methyl-ethyl)pyrimidin-5-yl]-2-methylimidazo[1,2a-]pyridin-3-yl}methyl)-6-(3-hydroxyoxetan-3-yl)-2-methyl-1,4-benzoxazin-3-one;
8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)-pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}-methyl)-N-isopropyl-3-oxo-1,4-benzoxazine-6-carboxamide;
4-({7-Fluoro-6-[2-(1-hydroxy-1-methylethyl)-pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}-methyl)-N-isopropyl-2-methyl-3-oxopyrido[3,2-b]-[1,4]oxazine-6-carboxamide;
(2R)-8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methyl-ethyl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}methyl)-6-(3-methoxyoxetan-3-yl)-2-methyl-1,4-benzoxazin-3-one;
(2S)-8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methyl-ethyl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}methyl)-6-(1-hydroxy-1-methylethyl)-2-methyl-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methyl-ethyl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-6-(methyl sulfanyl)-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-6-(methyl sulfinyl)-1,4-benzoxazin-3-one;
(2R)-8-Fluoro-4-({7-fluoro-6-[2-(1-hydroxy-1-methylethyl)pyrimidin-5-yl]-2-methyl-imidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-6-(methyl sulfonyl)-1,4-benzoxazin-3-one;
1-({7-Fluoro-6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}methyl)-3-methyl-3,4-dihydroquinolin-2(1H)-one;
5-Fluoro-1-({7-fluoro-6-[2-(2-hydroxypropan-2-yl)-pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}-methyl)-3-methyl-3,4-dihydroquinolin-2(1H)-one;
(8-anti)-3-(5-{7-Fluoro-3-[(5-fluoro-3-methyl-2-oxo-3,4-dihydroquinolin-1 (2H)-yl)methyl]-2-methyl-imidazo[1,2-a]pyridin-6-yl}pyrimidin-2-yl)-3-azabicyclo[3.2.1]octane-8-carboxylic acid;
(2R)-8-Fluoro-4-({6-[2-(2-hydroxypropan-2-yl)-4-methylpyrimidin-5-yl]-2-methylimidazo[1,2-a]-pyrazin-3-yl}methyl)-2-methyl-2H-1,4-benzoxazin-3 (4H)-one;
(2S)-8-Fluoro-4-({7-fluoro-2-methyl-6-[2-(3-oxo-piperazin-1-yl)pyrimidin-5-yl]imidazo[1,2-a]pyridin-3-yl}methyl)-2-methyl-2H-1,4-benzoxazin-3(4H)-one;
(2S)-8-Fluoro-4-({7-fluoro-6-[6-(4-hydroxytetrahydro-2H-pyran-4-yl)pyridin-3-yl]-2-methylimidazo[1,2-a]-pyridin-3-yl}methyl)-2-methyl-2H-1,4-benzoxazin-3 (4H)-one;
(2R)-8-Fluoro-4-({6-[6-(4-hydroxytetrahydro-2H-pyran-4-yl)pyridin-3-yl]-2-methylimidazo[1,2-a]-pyrazin-3-yl}methyl)-2-methyl-2H-1,4-benzoxazin-3 (4H)-one;
4-({7-Fluoro-6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a],pyridin-3-yl}methyl)-2H-1,4-b enzothiazin-3 (4H)-one 1-oxide;
4-({7-Fluoro-6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2-a]pyridin-3-yl}methyl)-2H-1,4-b enzothiazin-3 (4H)-one;
or
N-[(2R)-8-Fluoro-4-({7-fluoro-6-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-2-methylimidazo[1,2a-]pyridin-3-yl}methyl)-2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl]-2-methylpropanamide.

195 more elements

Dependencies are inferred from the claim text.

Facts

Application: 15/100,825Filed 8 Dec 2014
Priority: GB 1321738.59 Dec 2013
Published: US 2016/0297837 A113 Oct 2016
Granted: 16 Jan 2018
Term ends: Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07D 519/00
Heterocyclic compounds containing more than one system of two or more relevant
A61K 31/4355
Ortho- or peri-condensed with heterocyclic ring systems: the heterocyclic ring system containing a five-membered ring having oxygen as a ring…
A61K 31/4709
Quinolines; Isoquinolines: non-condensed quinolines and containing further heterocyclic rings
A61K 31/538
1,4-Oxazines, e.g. morpholine: ortho- or peri-condensed with carbocyclic ring systems