IP Library › Granted Patent US 8,658,641

Granted Patent B2

US 8,658,641 · App. 13/124,889 · Granted Feb 25, 2014

Fused, spirocyclic heteroaromatic compounds for the treatment of bacterial infections

Inventors: Kevin Barvian (Waltham, MA); Gregory Steven Basarab (Waltham, MA); Madhusudhan Reddy Gowravaram (Waltham, MA); Sheila Irene Hauck (Waltham, MA); Fei Zhou (Waltham, MA)

Assignee: AstraZeneca AB

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Quick Facts

Patent No.: US 8,658,641
App. No.: 13/124,889
Granted: Feb 25, 2014
Kind: B2

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Abstract

The present invention relates to compounds of Formula (I); to pharmaceutically acceptable salts thereof, to methods of using them to treat bacterial infections, and to methods for their preparation.

Claims (352)

1. A compound of Formula (I),

or a pharmaceutically acceptable salt thereof, wherein:

Ring A is a fused morpholine optionally substituted on carbon with one or two R 4 ;

W is —O or —S—

X is N or C—H;

Y is N or C—R 3 ;

R 1 is selected from halo, —CN, carbocyclyl, heterocyclyl, —OR 1a , —N(R 1a ) 2 , and —C(O)N(R 1a ) 2 , wherein said C 1-6 alkyl, carbocyclyl, and heterocyclyl are optionally substituted on carbon with one or more R 10 , and wherein any —NH— moiety of said heterocyclyl is optionally substituted with R 10 *;

R 1a in each occurrence is independently selected from H, carbocyclyl, and heterocyclyl, wherein said C 1-6 alkyl, carbocyclyl, and heterocyclyl in each occurrence are optionally and independently substituted on carbon with one or more R 10 , and wherein any —NH— moiety of said heterocyclyl is optionally substituted with R 10 *;

R 1b is C 1-6 alkyl;

R 3 is chlorine, fluorine or methyl;

R 4 is methyl;

R 10 in each occurrence is independently selected from —CN, carbocyclyl, heterocyclyl, —OR 10a , —SR 10a , —N(R 10a ) 2 , —N(R 10a )C(O)R 10b , —C(O)R 10b , —C(O) 2 R 10a , —C(O)N(R 10a ) 2 , and wherein said C 1-6 alkyl, carbocyclyl and heterocyclyl in each occurrence are optionally and independently substituted on carbon with one or more R a , and wherein any —NH— moiety of said heterocyclyl is optionally substituted with R a *;

R 10 * in each occurrence is independently selected from C 1-6 alkyl, —C(O)R 10b and —C(O) 2 R 10a , wherein said C 1-6 alkyl each occurrence is optionally and independently substituted on carbon with one or more R a ;

R 10a in each occurrence is independently selected from H, C 1-6 alkyl and heterocyclyl, wherein said C 1-6 alkyl and heterocyclyl in each occurrence are optionally and independently substituted on carbon with one or more R a , and wherein any —NH— moiety of said heterocyclyl is optionally substituted with R a *;

R a in each occurrence is independently selected from halo, —CN, C 1-6 alkyl and —OR m ;

R a * in each occurrence is C 1-6 alkyl; and

R m in each occurrence is independently selected from H, C 1-6 alkyl, carbocyclyl, and heterocyclyl.

2. The compound of Formula (I), or a pharmaceutically acceptable salt thereof, as claimed in claim 1 , wherein W is —O—.

3. The compound of Formula (I), or a pharmaceutically acceptable salt thereof, as claimed in claim 2 , wherein X is C—H.

4. The compound of (I), or a pharmaceutically acceptable salt thereof, as claimed in claim 3 , wherein R 3 is chlorine.

5. The compound of (I), or a pharmaceutically acceptable salt thereof, as claimed in claim 3 , wherein R 3 is fluorine.

6. A compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

(2R,4S,4aS)-8-Amino-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-Fluoro-2,4,8-trimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-Fluoro-2,4-dimethyl-8-phenyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-8-Cyclopropyl-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-Fluoro-2,4-dimethyl-8-pyridin-2-yl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4,8-trimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-8-(4-acetylpiperazin-1-yl)-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-8-(benzylamino)-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-[(1,3-thiazol-2-ylmethyl)amino]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-8-[(1H-imidazol-4-ylmethyl)amino]-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-{[(1-methyl-1H-pyrazol-4-yl)methyl]amino}-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-{[(5-methyl-1,2-oxazol-3-yl)methyl]amino}-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-[(pyridin-2-ylmethyl)amino]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-[(pyridin-3-ylmethyl)amino]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-[(pyridin-4-ylmethyl)amino]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-8-[(cyclopropylmethyl)amino]-1-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-8-[(cyclohexylmethyl)amino]-1-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-[(tetrahydro-2H-pyran-4-ylmethyl)amino]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

tert-butyl 4-[(2R,4S,4aS)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-1,1′,2,3′,4,4′,4a,6′-octahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidin]-8-yl]piperazine-1-carboxylate;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(piperazin-1-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(morpholin-4-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-8-(diethylamino)-1-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-8-(dimethylamino)-1-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(pyrrolidin-1-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-8-(azepan-1-yl)-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

N-{1-[(2R,4S,4aS)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-1,1′,2,3′,4,4′,4a,6′-octahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidin]-8-yl]-1H-pyrazol-3-yl}acetamide;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-[3-(trifluoromethyl)-1H-pyrazol-1-yl]-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-8-[3-(difluoromethyl)-5-methyl-1H-pyrazol-1-yl]-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(propylamino)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-8-[benzyl(methyl)amino]-1-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

3-amino-1-[(2R,4S,4aS)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-1,1′,2,3′,4,4′,4a,6′-octahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidin]-8-yl]-1H-pyrazole-4-carbonitrile;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-[4-(pyrimidin-4-yl)-1H-pyrazol-1-yl]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-[4-(pyrazin-2-yl)-1H-pyrazol-1-yl]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-8-(4-iodo-1H-pyrazol-1-yl)-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

ethyl 1-[(2R,4S,4aS)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-1,1′,2,3′,4,4′,4a,6′-octahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidin]-8-yl]-1H-pyrazole-4-carboxylate;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(pyridin-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-chloro-8-cyclopropyl-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(6-methylpyridin-3-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(1,3-thiazol-5-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(pyrimidin-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(pyrimidin-4-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(pyrimidin-5-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(pyridazin-4-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(pyridin-4-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(pyridin-3-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(1,3-thiazol-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-chloro-8-(methoxymethyl)-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-[methyl(propyl)amino]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)trione;

(2R,4S,4aS)-11-fluoro-8-methoxy-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-8-(benzyloxy)-1-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(1H-1,2,4-triazol-1-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(3-methyl-1H-1,2,4-triazol-1-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

1-[(2R,4S,4aS)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-1,1′,2,3′,4,4′,4a,6′-octahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidin]-8-yl]-1H-1,2,4-triazole-3-carbonitrile;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(2H-1,2,3-triazol-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(1H-1,2,3-triazol-1-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-8-(1H-imidazol-1-yl)-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-[4-(trifluoromethyl)-1H-imidazol-1-yl]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(4-methyl-1H-pyrazol-1-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-8-(4-chloro-1H-pyrazol-1-yl)-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(methylsulfanyl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-8-(3,5-dimethyl-1H-pyrazol-1-yl)-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(1H-pyrazol-4-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(2-methyl-1,3-oxazol-4-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(5-methyl-1,2-oxazol-3-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-8-(3,5-dimethyl-1,2-oxazol-4-yl)-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aR)-11-fluoro-2,4-dimethyl-8-(1-methyl-1H-imidazol-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(1-methyl-1H-imidazol-4-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(1-methyl-1H-imidazol-5-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(4-methyl-1,3-thiazol-5-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(4-methyl-1,2,3-thiadiazol-5-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(pyridazin-3-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(pyrimidin-4-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4,8-trimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]thiazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(pyridin-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]thiazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4,8-trimethyl-1,2,3,4,4a,6-hexahydro-1′H-spiro[isoxazolo[4,5-g]pyrido[1,2-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-8-(3-chloropyrazin-2-yl)-11-fluoro-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-8-(6-chloropyrazin-2-yl)-11-fluoro-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(5-(methylthio)pyrazin-2-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-8-((1H-1,2,4-triazol-1-yl)methyl)-11-fluoro-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(pyridin-4-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-fluoro-8-(5-hydroxy-1,3,4-oxadiazol-2-yl)-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-[4-(morpholin-4-ylcarbonyl)-1,3-thiazol-2-yl]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-[4-(morpholin-4-ylcarbonyl)-1,3-thiazol-5-yl]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

2-[(2R,4S,4aS)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-1,1′,2,3′,4,4′,4a,6′-octahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidin]-8-yl]-N,N-dimethyl-1,3-thiazole-4-carboxamide;

5-[(2R,4S,4aS)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-1,1′,2,3′,4,4′,4a,6′-octahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidin]-8-yl]-1,3-thiazole-4-carbonitrile;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(1-methyl-1H-imidazol-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-2,4,11-trimethyl-8-(1,3-thiazol-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-rel-11-fluoro-2,4-dimethyl-8-(6-methylpyridin-3-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(trifluoromethyl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-8-(difluoromethyl)-11-fluoro-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)—N-(2,2-difluoroethyl)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-8-(3,3-difluoroazetidine-1-carbonyl)-1-fluoro-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(thiazol-2-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-fluoro-8-(furan-2-yl)-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(thiazol-5-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-fluoro-8-(2-fluorophenyl)-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(tetrahydro-2H-pyran-4-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-2,4,11-trimethyl-8-(pyrazin-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(pyridyin-2-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(pyridyin-4-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(pyridyin-3-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(pyrazin-2-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(thiazol-2-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(1-methyl-1H-imidazol-2-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-1-Chloro-2,4-dimethyl-8-(4-methylthiazol-2-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-1-Chloro-2,4-dimethyl-8-(1-methyl-1H-imidazol-2-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(thiazol-5-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(2,4-dichlorothiazol-5-yl)-2,4,4a,6-tetrahydro-1H, 1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-Chloro-2,4-dimethyl-8-(2-methylthiazol-5-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(1-methyl-1H-1,2,4-triazol-5-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(2-bromothiazol-5-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-chloro-2,4-dimethyl-8-(pyrazin-2-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

4-((2R,4S,4aS)-11-chloro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-yl)-2-fluorobenzonitrile;

(2R,4S,4aS)-11-Chloro-2,4-dimethyl-8-(5-methylthiazol-2-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

5-((2R,4S,4aS)-11-chloro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-yl)picolinamide;

(2R,4S,4aS)-11-Chloro-2,4,8-trimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-Chloro-N,2,4-trimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-chloro-N-ethyl-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-Chloro-N-isopropyl-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)—N-tert-butyl-11-chloro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-Chloro-2,4-dimethyl-N-neopentyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-Chloro-8-(3,3-difluoroazetidine-1-carbonyl)-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)—N-benzyl-11-chloro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-chloro-N-(4-cyanobenzyl)-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-chloro-N-(3-cyanobenzyl)-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-fluoro-N,N,2,4-tetramethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)—N-ethyl-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)—N-ethyl-11-fluoro-N,2,4-trimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-fluoro-N,2,4-trimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro- 1 H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-fluoro-2,4-diethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-fluoro-N-(2-methoxyethyl)-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)—N-tert-butyl-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-N-(tetrahydro-2H-pyran-4-yl)-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-fluoro-N-isopropyl-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(pyrimidin-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)—N-cyclopropyl-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)—N-(cyclopropylmethyl)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-N-(thiophen-2-ylmethyl)-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-N-(pyridin-4-ylmethyl)-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)—N-(cyclohexylmethyl)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-N-(1-methylazetidin-3-yl)-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-N-((1-methyl-1H-pyrazol-3-yl)methyl)-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-N-((1-methyl-1H-pyrazol-5-yl)methyl)-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)—N-(1,3-dimethoxy-2-(methoxymethyl)propan-2-yl)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(pyrazin-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(5-morpholinopyrazin-2-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-fluoro-8-(6-methoxypyrazin-2-yl)-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(2-(methylthio)pyrimidin-4-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-fluoro-2,4-dimethyl-8-(2-(methylsulfonyl)pyrimidin-4-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-fluoro-8-(2-(2-methoxyethylamino)pyrimidin-4-yl)-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-fluoro-8-(2-(2-hydroxyethylamino)pyrimidin-4-yl)-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-fluoro-8-(2-methoxypyrimidin-4-yl)-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

4-((2R,4S,4aS)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-yl)pyrimidine-2-carbonitrile;

(2R,4S,4aS)-8-(2-aminopyrimidin-4-yl)-11-fluoro-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-fluoro-8-(2-hydroxypyrimidin-4-yl)-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-11-Fluoro-2,4-dimethyl-8-(2-morpholinopyrimidin-4-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-8-(6-(Dimethylamino)pyrazin-2-yl)-1-fluoro-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-Fluoro-2,4-dimethyl-8-(1-methyl-1H-1,2,4-triazol-5-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-Fluoro-2,4-dimethyl-8-(piperazin-1-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2R,4S,4aS)-8-Chloro-11-fluoro-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-Fluoro-2,4-dimethyl-2′,4′,6′-trioxo-1,1′,2,3′,4,4′,4a,6′-octahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-8-carbonitrile;

ethyl 2-[(2R,4S,4aS)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-1,1′,2,3′,4,4′,4a,6′-octahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidin]-8-yl]-1,3-thiazole-4-carboxylate;

(2R,4S,4aS)-11-fluoro-8-(hydroxymethyl)-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-11-fluoro-8-[4-(hydroxymethyl)-1H-pyrazol-1-yl]-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-8-Amino-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-Fluoro-2,4,8-trimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-Fluoro-2,4-dimethyl-8-phenyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-8-Cyclopropyl-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-Fluoro-2,4-dimethyl-8-pyridin-2-yl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4,8-trimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-8-(4-acetylpiperazin-1-yl)-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-8-(benzylamino)-1-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-[(1,3-thiazol-2-ylmethyl)amino]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-8-[(1H-imidazol-4-ylmethyl)amino]-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-{[(1-methyl-1H-pyrazol-4-yl)methyl]amino}-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-{[(5-methyl-1,2-oxazol-3-yl)methyl]amino}-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-[(pyridin-2-ylmethyl)amino]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-[(pyridin-3-ylmethyl)amino]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-[(pyridin-4-ylmethyl)amino]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-8-[(cyclopropylmethyl)amino]-1-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-8-[(cyclohexylmethyl)amino]-1-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-[(tetrahydro-2H-pyran-4-ylmethyl)amino]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

tert-butyl 4-[(2S,4R,4aR)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-1,1′,2,3′,4,4′,4a,6′-octahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidin]-8-yl]piperazine-1-carboxylate;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(piperazin-1-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(morpholin-4-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-8-(diethylamino)-1-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-8-(dimethylamino)-1-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(pyrrolidin-1-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-8-(azepan-1-yl)-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

N-{1-[(2S,4R,4aR)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-1,1′,2,3′,4,4′,4a,6′-octahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidin]-8-yl]-1H-pyrazol-3-yl}acetamide;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-[3-(trifluoromethyl)-1H-pyrazol-1-yl]-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-8-[3-(difluoromethyl)-5-methyl-1H-pyrazol-1-yl]-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(propylamino)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-8-[benzyl(methyl)amino]-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

3-amino-1-[(2S,4R,4aR)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-1,1′,2,3′,4,4′,4a,6′-octahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidin]-8-yl]-1H-pyrazole-4-carbonitrile;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-[4-(pyrimidin-4-yl)-1H-pyrazol-1-yl]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-[4-(pyrazin-2-yl)-1H-pyrazol-1-yl]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-8-(4-iodo-1H-pyrazol-1-yl)-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

ethyl 1-[(2S,4R,4aR)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-1,1′,2,3′,4,4′,4a,6′-octahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidin]-8-yl]-1H-pyrazole-4-carboxylate;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(pyridin-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-chloro-8-cyclopropyl-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(6-methylpyridin-3-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(1,3-thiazol-5-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(pyrimidin-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(pyrimidin-4-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(pyrimidin-5-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(pyridazin-4-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(pyridin-4-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(pyridin-3-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(1,3-thiazol-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-chloro-8-(methoxymethyl)-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-[methyl(propyl)amino]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)trione;

(2S,4R,4aR)-11-fluoro-8-methoxy-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)l-8-(benzyloxy)-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(1H-1,2,4-triazol-1-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(3-methyl-1H-1,2,4-triazol-1-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-1,1′,2,3′,4,4′,4a,6′-octahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidin]-8-yl]-1H-1,2,4-triazole-3-carbonitrile;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(2H-1,2,3-triazol-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(1H-1,2,3-triazol-1-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-8-(1H-imidazol-1-yl)-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-[4-(trifluoromethyl)-1H-imidazol-1-yl]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(4-methyl-1H-pyrazol-1-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-8-(4-chloro-1H-pyrazol-1-yl)-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(methylsulfanyl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-8-(3,5-dimethyl-1H-pyrazol-1-yl)-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(1H-pyrazol-4-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(2-methyl-1,3-oxazol-4-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(5-methyl-1,2-oxazol-3-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-8-(3,5-dimethyl-1,2-oxazol-4-yl)-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(1-methyl-1H-imidazol-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(1-methyl-1H-imidazol-4-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(1-methyl-1H-imidazol-5-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(4-methyl-1,3-thiazol-5-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(4-methyl-1,2,3-thiadiazol-5-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(pyridazin-3-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(pyrimidin-4-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4,8-trimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]thiazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(pyridin-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]thiazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4,8-trimethyl-1,2,3,4,4a,6-hexahydro-1′H-spiro[isoxazolo[4,5-g]pyrido[1,2-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-8-(3-chloropyrazin-2-yl)-11-fluoro-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-8-(6-chloropyrazin-2-yl)-11-fluoro-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(5-(methylthio)pyrazin-2-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-8-((1H-1,2,4-triazol-1-yl)methyl)-1-fluoro-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(pyridin-4-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione

(2S,4R,4aR)-11-fluoro-8-(5-hydroxy-1,3,4-oxadiazol-2-yl)-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-[4-(morpholin-4-ylcarbonyl)-1,3-thiazol-2-yl]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-[4-(morpholin-4-ylcarbonyl)-1,3-thiazol-5-yl]-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(1-methyl-1H-imidazol-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-2,4,11-trimethyl-8-(1,3-thiazol-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(6-methylpyridin-3-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2R,4S,4aS)-rel-11-fluoro-2,4-dimethyl-8-(trifluoromethyl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-8-(difluoromethyl)-11-fluoro-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)—N-(2,2-difluoroethyl)-1-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-8-(3,3-difluoroazetidine-1-carbonyl)-1-fluoro-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-fluoro-8-(furan-2-yl)-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(thiazol-5-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-fluoro-8-(2-fluorophenyl)-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(tetrahydro-2H-pyran-4-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-2,4,11-trimethyl-8-(pyrazin-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(pyridyin-2-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(pyridyin-4-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(pyridyin-3-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(pyrazin-2-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(thiazol-2-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(1-methyl-1H-imidazol-2-yl)-2,4,4a,6-tetrahydro-1H,1H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-Chloro-2,4-dimethyl-8-(1-methyl-1H-imidazol-2-yl)-2,4,4a,6-tetrahydro-1H,1H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-Chloro-2,4-dimethyl-8-(1-methyl-1H-imidazol-2-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(thiazol-5-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(2,4-dichlorothiazol-5-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-Chloro-2,4-dimethyl-8-(2-methylthiazol-5-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(1-methyl-1H-1,2,4-triazol-5-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(2-bromothiazol-5-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-chloro-2,4-dimethyl-8-(pyrazin-2-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

4-((2S,4R,4aR)-11-chloro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-yl)-2-fluorobenzonitrile;

(2S,4R,4aR)-11-Chloro-2,4-dimethyl-8-(5-methylthiazol-2-yl)-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

5-((2S,4R,4aR)-11-chloro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-yl)picolinamide;

(2S,4R,4aR)-11-Chloro-2,4,8-trimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-Chloro-N,2,4-trimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-11-chloro-N-ethyl-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-Chloro-N-isopropyl-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)—N-tert-butyl-11-chloro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-11-Chloro-2,4-dimethyl-N-neopentyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-11-Chloro-8-(3,3-difluoroazetidine-1-carbonyl)-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)—N-benzyl-11-chloro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-11-chloro-N-(4-cyanobenzyl)-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-11-chloro-N-(3-cyanobenzyl)-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a][1,5]naphthyridine-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-11-fluoro-N,N,2,4-tetramethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)—N-ethyl-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)—N-ethyl-11-fluoro-N,2,4-trimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-11-fluoro-N,2,4-trimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-11-fluoro-N-(2-methoxyethyl)-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)—N-tert-butyl-1-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-N-(tetrahydro-2H-pyran-4-yl)-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-11-fluoro-N-isopropyl-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(pyrimidin-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-fluoro-4,8-dimethyl-2-(trifluoromethyl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)—N-cyclopropyl-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)—N-(cyclopropylmethyl)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-N-(thiophen-2-ylmethyl)-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-N-(pyridin-4-ylmethyl)-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)—N-(cyclohexylmethyl)-11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-N-(1-methylazetidin-3-yl)-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-N-((1-methyl-1H-pyrazol-3-yl)methyl)-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-N-((1-methyl-1H-pyrazol-5-yl)methyl)-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)—N-(1,3-dimethoxy-2-(methoxymethyl)propan-2-yl)-1-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-2,2′,3′,4,4a,4′,6,6′-octahydro-1H,1′H-spiro[isoxazolo[4,5g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-8-carboxamide;

(2S,4R,4aR)-11-fluoro-2,4-dimethyl-8-(pyrazin-2-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-8-(6-(Dimethylamino)pyrazin-2-yl)-1-fluoro-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-Fluoro-2,4-dimethyl-8-(piperazin-1-yl)-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione;

(2S,4R,4aR)-11-Fluoro-2,4-dimethyl-2′,4′,6′-trioxo-1,1′,2,3′,4,4′,4a,6′-octahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-8-carbonitrile;

ethyl 2-[(2S,4R,4aR)11-fluoro-2,4-dimethyl-2′,4′,6′-trioxo-1,1′,2,3′,4,4′,4a,6′-octahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidin]-8-yl]-1,3-thiazole-4-carboxylate;

(2S,4R,4aR)-11-fluoro-8-(hydroxymethyl)-2,4-dimethyl-2,4,4a,6-tetrahydro-1H,1′H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(3′H)-trione;

(2S,4R,4aR)-11-fluoro-8-[4-(hydroxymethyl)-1H-pyrazol-1-yl]-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione, or a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof, as claimed in claim 1 , and a pharmaceutically acceptable carrier, diluent or excipient.

8. A pharmaceutical composition comprising a compound as claimed in claim 6 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or excipient.

Assignments (5)

NUNC PRO TUNC ASSIGNMENT Recorded Feb 20, 2025

From: ENTASIS THERAPEUTICS LIMITED

To: ENTASIS THERAPEUTICS INC.

Reel/Frame 070271/0396 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 7, 2015

From: ASTRAZENECA AB

To: ENTASIS THERAPEUTICS LIMITED

Reel/Frame 036005/0799 →

CORRECTIVE ASSIGNMENT TO CORREC THE ASSIGNEE, PREVIOUSLY RECORDED ON REEL 026408 FRAME 0707. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Dec 13, 2011

From: BARVIAN, KEVIN; BASARAB, GREGORY STEVEN; GOWRAVARAM, MADHUSUDHAN REDDY; HAUCK, SHEILA IRENE; ZHOU, FEI

To: ASTRAZENECA PHARMACEUTICALS LP

Reel/Frame 027572/0204 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 8, 2011

From: ASTRAZENECA PHARMACEUTICALS LP

To: ASTRAZENECA AB

Reel/Frame 026408/0602 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 8, 2011

From: BARVIAN, KEVIN; BASARAB, GREGORY STEVEN; GOWRAVARAM, MADHUSUDHAN REDDY; HAUCK, SHEILA IRENE; ZHOU, FEI

To: ASTRAZENECA AB

Reel/Frame 026408/0707 →

Continuity (2)

Provisional Application 61105189 · Oct 14, 2008

Related Publication 20110245224A1 · Oct 6, 2011