Bicyclic-fused heteroaryl or aryl compounds

1. A compound of Formula IIc, IId, IIe, IIf or IIg,

wherein

R 1 is C 1 -C 6 alkyl; C 2 -C 6 alkenyl; C 2 -C 6 alkynyl; —(CR 3a R 3b ) m -(3- to 7-membered cycloalkyl); or —(CR 3a R3 b ) m -(3- to 7-membered heterocycloalkyl) having one to three heteroatoms; wherein said alkyl, alkenyl, alkynyl, cycloalkyl or heterocycloalkyl is optionally substituted with one to five halogen, deuterium, —OR 5 , —SR 5 , —NR 11a R 11b , cyano, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl or —C 1 -C 6 alkoxy;

R 2 is —(CR 3a R3 b ) m -(3- to 10-membered heterocycloalkyl) having one to three heteroatoms, wherein said heterocycloalkyl is optionally substituted at a carbon atom with one to five R 4 and wherein, if the heteroatom is N, said N is optionally substituted with R 4′ ;

R 3a and R 3b are each independently hydrogen or C 1 -C 3 alkyl;

R 4 for each occurrence is independently and optionally halogen, cyano, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, oxo, —OR 5 , —SR 5 , —S(O)R 9 , —S(O) 2 R9, —C(O)R 10 , —(CR 3a R 3b ) n -(3- to 7-membered cycloalkyl) or —(CR 3a R 3b ) n -(4- to 7-membered heterocycloalkyl) wherein said alkyl, cycloalkyl and heterocycloalkyl are each optionally and independently substituted with one to five deuterium, halogen, —OR 5 , —SR 5 , —NR 11a R 11b , cyano, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl C 1 -C 6 alkoxy or NR 11a R 11b ; or two R 4 taken together with the respective carbons to which each are bonded form a 3- to 6-membered cycloalkyl or 4- to 6-membered heterocycloalkyl, wherein said cycloalkyl or heterocycloalkyl is optionally substituted with one to three halogen, deuterium, —OR 5 , —SR 5 , —NR 11a R 11b , cyano or C 1 -C 6 alkyl or C 1 -C 6 alkoxy, wherein the alkyl or alkoxy is optionally substituted with halogen, deuterium, —OR 5 , —NR 11a R 11b , or cyano; and wherein, if a heteroatom on said heterocycloalkyl is N, said N is optionally substituted with R 4′ ;

R 4′ is independently C 1 -C 6 alkyl, C 2 -C 6 alkenyl, —S(O)R 9 , —S(O) 2 R 9 , —C(O)R 10 , C(O)(CH 2 ) t CN; wherein said alkyl is optionally substituted with NH 2 , cyano or halogen —(CR 3a R 3b ) n -(3- to 7-membered cycloalkyl), —(CR 3a R 3b ) n -(4- to 10-membered heterocycloalkyl), wherein said alkyl, alkenyl, cycloalkyl, or heterocycloalkyl is each optionally and independently substituted with one to five deuterium, halogen, OH, cyano or C 1 -C 6 alkoxy; or R 4 and R 4′ taken together with the respective atoms to which each are bonded form a 3- to 6-membered cycloalkyl or 4- to 6-membered heterocycloalkyl, wherein said cycloalkyl or heterocycloalkyl is optionally substituted with one to three halogen, deuterium, —OR 5 , —SR 5 , —NR 11a R 11b , cyano, C 1 -C 6 alkyl or C 1 -C 6 alkoxy, wherein the alkyl or alkoxy is optionally substituted with halogen, deuterium, —OR 5 , —SR 5 , —NR 11a R 11b or cyano;

R 5 is hydrogen or C 1 -C 6 alkyl, wherein said alkyl is optionally substituted with halogen;

R 6 is —C(O)NHR 7 or cyano;

R 7 is hydrogen or C 1 -C 6 alkyl;

R 8 is independently hydrogen, halogen, cyano, —NR 11a R 11b , C 1 -C 6 alkyl, 5- to 6-membered heteroaryl or 5- to 6-membered aryl, wherein said alkyl or heteroaryl or aryl is optionally substituted with one to three halogen, —NR 11a R 11b , C 1 -C 3 alkyl or oxo;

R 8 is hydrogen, deuterium, halogen, cyano, —OR 5 , or NR 11a NR 11 b;

R 9 is —(CR 3a R 3b ) p —(C 1 -C 3 alkyl), —(CR 3a R 3b ) p —(4- to 6-membered cycloalkyl), —(CR 3a R 3b ) p —(4- to 6-membered heterocycloalkyl) or —(CR 3a R 3b ) p —(C 5 -C 9 aryl), wherein said alkyl, cycloalkyl, heterocycloalkyl or aryl is each optionally substituted with fluoro or C 1 -C 3 alkyl;

R 10 is C 1 -C 6 alkyl, wherein said alkyl is optionally substituted with fluoro or cyano;

R 11a and R 11b are each independently hydrogen or C 1 -C 6 alkyl, wherein said alkyl is optionally substituted with OH;

m is independently 0, 1 or 2;

n is independently 0 or 1;

p is independently 0 or 1; and

t is 0, 1, 2 or 3;

or a pharmaceutically acceptable salt of said compound or a tautomer of said compound or said salt.

2. The compound of claim 1 wherein

R 1 is C 1 -C 4 alkyl; C 2 -C 4 alkenyl; C 2 -C 4 alkynyl; —(CR 3a R 3b ) m -(3- to 6-membered cycloalkyl); or —(CR 3a R3 b ) m -(3- to 5-membered heterocycloalkyl) having one to three heteroatoms; wherein said alkyl, alkenyl, alkynyl, cycloalkyl or heterocycloalkyl is optionally substituted with one to three halogen, deuterium, —OR 5 , —SR 5 , —NR 11a R 11b , cyano, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl or —C 1 -C 6 alkoxy;

R 3a and R 3b are each independently hydrogen or C 1 -C 3 alkyl;

R 6 is —C(O)NHR 7 or cyano;

R 7 is hydrogen; and

m is independently 0 or 1;

or a pharmaceutically acceptable salt of said compound or a tautomer of said compound.

3. The compound of claim 2 wherein R 1 is fluoromethyl; difluoromethyl; trifluoromethyl; methyl, ethyl, propyl or isopropyl, each optionally substituted with one to three fluoro or deuterium; allene, propargyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclopropylmethyl, oxetane or tetrahydrofuran, each of which is optionally substituted with fluoro or C 1 -C 3 alkyl; or a pharmaceutically acceptable salt of said compound or a tautomer of said compound or said salt.

4. The compound of claim 3 wherein the heterocycloalkyl of R 2 is selected from pyrrolidinyl, pyrrolidin-2-onyl, piperidinyl, piperidin-2-onyl, octahydro-1H-pyrrolo[3,4-c]pyridinyl, oxazolidinyl, oxazolidin-2-onyl, 1,3-oxazinan-2-onyl, imidazolidinyl, imidazolidin-2-onyl, morpholinyl, morpholin-3-onyl, thiazyl, isothiazyl, isothiazolidine-1,1-dioxidyl, 1,2-thiazinane 1,1-dioxidyl, hexahydrocyclopenta[b]pyrrol-2(1H)-onyl, octahydrocyclopenta[c]pyrrolyl, azetidinyl, hexahydro-1H-indol-2(3H)-onyl, octahydro-1H-isoindolyl, azepanyl, tetrahydrofuranyl, 1,3-dioxolanyl, oxetanyl, 4-azepanyl, 1,4-oxazepanyl, tetrahydro-2H-pyranyl, 6,7-dihydro-5H-pyrrolo[1,2-a]imidazolyl, or 1,2,3,4-tetrahydroisoquinolinyl; wherein said heterocycloalkyl is optionally substituted with one to four R 4 ; or a pharmaceutically acceptable salt of said compound or a tautomer of said compound or said salt.

5. The compound of claim 4 wherein the heterocycloalkyl of R 2 is selected from

wherein said heterocycloalkyl is optionally substituted with one to four R 4 ;

or two R 4 taken together with the respective carbons to which each are bonded form a 3- to 6-membered cycloalkyl or 4- to 6-membered heterocycloalkyl, wherein said cycloalkyl or heterocycloalkyl is optionally substituted with one to three F, Cl, OH, cyano, C 1 -C 3 alkyl (optionally substituted with OH, F or Cl), C 1 -C 3 fluoroalkyl or C 1 -C 6 alkoxy;

R q is independently hydrogen, deuterium or C 1 -C 3 alkyl, wherein said alkyl is optionally substituted with halogen; and

R 3a and R 3b for each occurrence are independently hydrogen or C 1 -C 3 alkyl;

R 4 for each occurrence is independently and optionally halogen; C 1 -C 3 alkyl; C 2 -C 4 alkenyl; oxo; —OR 5 ; —C(O)R 10 ; —(CR 3a R 3b ) n -(3- to 5-membered cycloalkyl); or —(CR 3a R3 b ) n -(4- to 7-membered heterocycloalkyl) wherein said alkyl, cycloalkyl or heterocycloalkyl is each optionally and independently substituted with one to five deuterium, halogen, OH, cyano, C 1 -C 6 alkoxy or —NR 11a R 11b ; or two R 4 taken together with the respective carbons to which each are bonded form a cyclopropyl, cyclobutyl or cyclopentyl, wherein said cyclopropyl, cyclobutyl or cyclopentyl are optionally substituted with one to three halogen, OH, methyl, ethyl, propyl, C 1 -C 3 fluoroalkyl, C 1 -C 3 hydroxyalkyl, methoxy or ethoxy; or two R 4 taken together with the respective carbons to which each are bonded form a 4- to 6-membered heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with one to three fluoro, C 1 -C 3 alkyl, or C 1 -C 3 fluoroalkyl;

R 5 is hydrogen, methyl or ethyl;

R 9 is phenyl;

R 10 is C 1 -C 6 alkyl, wherein said alkyl is optionally substituted with fluoro or cyano; and

R 11a and R 11b are each independently H or C 1 -C 6 alkyl;

or a pharmaceutically acceptable salt thereof or a tautomer of said compound or said salt.

6. The compound of claim 5 wherein R 4 is selected from F, Cl, OH; C 1 -C 3 alkyl, optionally substituted with one to five deuterium, Cl, F, OH, C 1 -C 3 alkyl, C 1 -C 3 alkoxy; or two R 4 taken together with the respective carbons to which each are bonded form a cyclopropyl, cyclobutyl or cyclopentyl, wherein said cyclopropyl, cyclobutyl or cyclopentyl are optionally substituted with one to three Cl, F, OH, methyl, ethyl, propyl, C 1 -C 3 fluoroalkyl, C 1 -C 3 hydroxyalkyl, methoxy or ethoxy; or two R 4 taken together with the respective carbons to which each are bonded form a 4- to 6-membered heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with one to three fluoro, C 1 -C 3 alkyl, C 1 -C 3 fluoroalkyl, —C(O)(CH 2 ) t CN; or a pharmaceutically acceptable salt thereof or a tautomer of said compound or said salt.

7. The compound of claim 1 , wherein

R 1 is C 1 -C 6 alkyl or C 1 -C 6 cycloalkyl, wherein said alkyl or cycloalkyl is optionally substituted with deuterium, halogen, OH, cyano, C 1 -C 3 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy or C 1 -C 6 alkylthiolyl;

R 3a and R 3b are each independently hydrogen or C 1 -C 3 alkyl;

R 4 for each occurrence (one, two, three, four or five) is independently and optionally halogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl —OR 5 , —(CR 3a R 3b ) n -(3- to 6-membered cycloalkyl), —(CR 3a R 3b ) n -(4- to 6-membered heterocycloalkyl) wherein said alkyl, cycloalkyl or heterocycloalkyl is each optionally and independently substituted with one to five deuterium, halogen, OH, CN, —C(O)(CH 2 ) t CN or —C 1 -C 6 alkoxy; —NR 11a R 11b ; two R 4 taken together with the respective carbons to which each are bonded form a cyclopropyl, cyclobutyl or cyclopentyl, wherein said cyclopropyl, cyclobutyl or cyclopentyl is optionally substituted with one to three F, Cl, OH, methyl, ethyl, propyl, C 1 -C 3 fluoroalkyl, C 1 -C 3 difluoroalkyl, C 1 -C 3 trifluoroalkyl, C 1 -C 3 hydroxyalkyl, methoxy or ethoxy;

R 5 is hydrogen or C 1 -C 6 alkyl, wherein said alkyl is optionally substituted with fluoro;

R 8 is independently hydrogen, halogen, cyano, —NR 11a R 11b , C 1 -C 6 alkyl, 5- to 6-membered heteroaryl or aryl, wherein said alkyl or heteroaryl or aryl is optionally substituted with one, two or three halogen, —NR 11a R 11b , C 1 -C 3 alkyl or oxo;

R 8′ is hydrogen, deuterium, halogen or cyano;

R 10 is C 1 -C 6 alkyl, wherein said alkyl is optionally substituted with fluoro or cyano;

R 11a and R 11b are each independently hydrogen or C 1 -C 6 alkyl, wherein said alkyl is optionally substituted with OH;

n is independently 0 or 1; and

t is 1, 2 or 3;

or a pharmaceutically acceptable salt of said compound or a tautomer of said compound.

8. The compound of claim 7 wherein R 1 is C 1 -C 3 alkyl, wherein said alkyl is optionally substituted with one to three deuterium, F, Cl or C 1 -C 3 alkoxy; and R 3a and R 3b are each independently hydrogen or methyl; or a pharmaceutically acceptable salt of said compound or a tautomer of said compound.

9. The compound of claim 8 wherein R 4 for each occurrence is independently and optionally F; Cl; OH; or C 1 -C 3 alkyl, optionally substituted with one to five deuterium, Cl, F, OH, C 1 -C 3 alkyl, or C 1 -C 3 alkoxy; or two R 4 taken together with the carbons to which they are bonded form a cyclopropyl, cyclobutyl or cyclopentyl, wherein said cyclopropyl, cyclobutyl or cyclopentyl is optionally substituted with one to three Cl, F, OH, methyl, ethyl, propyl, C 1 -C 3 haloalkyl, C 1 -C 3 dihaloalkyl, C 1 -C 3 trihaloalkyl, C 1 -C 3 hydroxyalkyl, methoxy or ethoxy; or two R 4 taken together with the carbons to which they are bonded form a 4- to 6-membered heterocycloalkyl, wherein said heterocycloalkyl is optionally substituted with one to three fluoro, C 1 -C 3 alkyl, C 1 -C 3 fluoroalkyl or —C(O)(CH 2 ) t CN; or a pharmaceutically acceptable salt of said compound or a tautomer of said compound or salt.

10. The compound of claim 9 wherein R 1 is methyl, ethyl, propyl or isopropyl wherein each of said R 1 moieties are optionally substituted with deuterium, fluoro or methoxy; or a pharmaceutically acceptable salt of said compound or a tautomer of said compound.

11. The compound of claim 10 wherein each R 4 is independently and optionally selected from fluoro, OH, methyl, ethyl, vinyl, propyl, wherein said methyl, ethyl, vinyl or propyl are optionally substituted with one, two or three fluoro, OH or methoxy; or two R 4 taken together with the carbons to which they are bonded form a cyclopropyl, cyclobutyl or cyclopentyl, wherein said cyclopropyl, cyclobutyl or cyclopentyl are optionally substituted with one to three Cl, F, OH, methyl, fluoromethyl, difluoromethyl, trifluoromethyl, ethyl, methoxymethyl, propyl, C 1 -C 3 haloalkyl, C 1 -C 3 dihaloalkyl, C 1 -C 3 trihaloalkyl, C 1 -C 3 hydroxyalkyl, methoxy, or ethoxy; and

R 8 is independently hydrogen, halogen or C 1 -C 6 alkyl, wherein said alkyl is optionally substituted with fluoro;

or a pharmaceutically acceptable salt of said compound or a tautomer of said compound or said salt.

12. The compound of claim 1 wherein

wherein

R 1 is C 1 -C 6 alkyl, wherein said alkyl is optionally substituted with deuterium, halogen, OH, C 1 -C 3 alkyl, C 3 -C 6 cycloalkyl or C 1 -C 6 alkoxy;

R 3a and R 3b are each independently hydrogen or C 1 -C 3 alkyl;

R 4a and R 4b are each independently hydrogen, deuterium, fluoro, OH, —OR 5 , methyl, ethyl, vinyl, cyclopropyl or propyl, optionally substituted with one to five deuterium, fluoro, methoxy or OH;

R 4C and R 4d for each occurrence are independently and optionally halogen, OH, deuterium, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, —OR 5 , —(CR 3a R 3b ) n -(3- to 6-membered cycloalkyl), or —(CR 3a R3 b ) n -(4- to 6-membered heterocycloalkyl) wherein said alkyl, cycloalkyl and heterocycloalkyl are each optionally and independently substituted with one to five deuterium, halogen, OH, cyano, or C 1 -C 6 alkoxy; NH 2 ; or R 4C and R 4d taken together with the carbons to which they are bonded form a 4- to 7-membered heterocycloalkyl or a 3- to 7-membered cycloalkyl, wherein said heterocycloalkyl or cycloalkyl is optionally substituted with one to three fluoro, C 1 -C 3 alkyl or C 1 -C 3 fluoroalkyl; or

R 4a and R 4c taken together with the carbon to which they are bonded form a 4- to 7-membered heterocycloalkyl or a 3- to 7-membered cycloalkyl, wherein said heterocycloalkyl or cycloalkyl is optionally substituted with one to three fluoro, C 1 -C 3 alkyl or C 1 -C 3 fluoroalkyl;

R 5 is hydrogen or C 1 -C 6 alkyl, wherein said alkyl is optionally substituted with fluoro;

R 8 is hydrogen, halogen or C 1 -C 6 alkyl, wherein said alkyl is optionally substituted with halogen;

R 8′ is hydrogen, deuterium, halogen or cyano; and

n is independently 0 or 1;

or a pharmaceutically acceptable salt of said compound or a tautomer of said compound or said salt.

13. The compound of claim 12 wherein R 8 is hydrogen, methyl or fluoro; or a pharmaceutically acceptable salt of said compound or a tautomer of said compound or said salt.

14. The compound of claim 13 wherein R 1 is methyl, ethyl, isopropyl or propyl, optionally substituted with deuterium; or a pharmaceutically acceptable salt of said compound or a tautomer of said compound or said salt.

15. The compound of claim 14 wherein

R 4a is hydrogen; methyl, ethyl or propyl, optionally substituted with deuterium, fluoro, methoxy;

R 4b is hydrogen or fluoro;

R 4c is hydrogen or OH;

R 4d is hydrogen, fluoro, methoxy or OH; or methyl, optionally substituted with 1, 2 or 3 fluoro; or ethyl, optionally substituted with 1, 2, or 3 fluoro; or

R 4c and R 4d or alternatively R 4a and R 4c taken together with the carbons to which they are bonded form a cyclopropyl, optionally substituted with one to three fluoro, C 1 -C 3 alkyl or C 1 -C 3 fluoroalkyl;

or a pharmaceutically acceptable salt of said compound or a tautomer of said compound or said salt.

16. A compound of claim 1 selected from:

5-{[(2S)-5-oxopyrrolidin-2-yl]methoxy}-3-(propan-2-yloxy)naphthalene-2-carboxamide;

3-methoxy-5-{[(2S)-5-oxopyrrolidin-2-yl]methoxy}naphthalene-2-carboxamide;

5-{[(2S,4S)-4-fluoro-4-methyl-5-oxopyrrolidin-2-yl]methoxy}-3-methoxynaphthalene-2-carboxamide;

5-{[(2S,4R)-4-fluoro-4-(hydroxymethyl)-5-oxopyrrolidin-2-yl]methoxy}-3-methoxynaphthalene-2-carboxamide;

3-methoxy-5-{[(2S,3R)-3-methyl-5-oxopyrrolidin-2-yl]methoxy}naphthalene-2-carboxamide;

5-{[(2S,3S,4S)-4-fluoro-3-methyl-5-oxopyrrolidin-2-yl]methoxy}-3-methoxynaphthalene-2-carboxamide;

8-fluoro-5-{[(2S,3S,4S)-4-fluoro-3-methyl-5-oxopyrrolidin-2-yl]methoxy}-3-methoxynaphthalene-2-carboxamide;

5-{[(2S,4R)-4-fluoro-5-oxo-4-(2,2,2-trifluoroethyl)pyrrolidin-2-yl]methoxy}-3-methoxynaphthalene-2-carboxamide;

4-{[(2S,4S)-4-ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-6-methoxyquinoline-7-carboxamide;

4-{[(2S,4S)-4-fluoro-4-methyl-5-oxopyrrolidin-2-yl]methoxy}-6-(propan-2-yloxy)quinoline-7-carboxamide;

4-{[(2S,3S,4S)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-6-methoxyquinoline-7-carboxamide;

4-{[(1R,2S,5S)-5-fluoro-6-methyl-4-oxo-3-azabicyclo[3.1.0]hex-2-yl]methoxy}-6-methoxyquinoline-7-carboxamide;

4-{[(1S,2S,5R)-6-fluoro-4-oxo-3-azabicyclo[3.1.0]hex-2-yl]methoxy}-6-methoxyquinoline-7-carboxamide;

4-{[(1R,2S,5S)-5-fluoro-4-oxo-3-azabicyclo[3.1.0]hex-2-yl]methoxy}-6-methoxyquinoline-7-carboxamide;

4-{[(1R,2S,5S)-6-(fluoromethyl)-4-oxo-3-azabicyclo[3.1.0]hex-2-yl]methoxy}-6-methoxyquinoline-7-carboxamide;

4-{[(2S,3S,4S)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-6-methoxyquinazoline-7-carboxamide; and

4-{[(2S,3S,4S)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-6-methoxyquinoline-7-carboxamide;

or a pharmaceutically acceptable salt of said compound or a tautomer of said compound or salt.

17. The compound of claim 16 selected from,

4-{[(2S,3S,4S)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-6-methoxyquinazoline-7-carboxamide; and

4-{[(2S,3S,4S)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-6-methoxyquinoline-7-carboxamide;

or a pharmaceutically acceptable salt thereof or a tautomer of said compound or said salt.

18. The compound selected from the group consisting of:

7-methoxyisoquinoline-6-carbonitrile;

1-chloro-7-hydroxyisoquinoline-6-carbonitrile;

1-chloro-7-methoxyisoquinoline-6-carbonitrile;

4-chloro-6-hydroxyquinoline-7-carbonitrile;

4-chloro-6-methoxyquinoline-7-carbonitrile;

6-methoxy-4-oxo-3,4-dihydroquinazoline-7-carbonitrile;

4-chloro-6-methoxyquinazoline-7-carbonitrile;

methyl 5-((tert-butyldiphenylsilyl)oxy)-3-hydroxy-2-naphthoate;

5-hydroxy-3-methoxy-2-naphthamide;

methyl 8-fluoro-5-hydroxy-3-methoxy-2-naphthoate;

8-fluoro-5-hydroxy-3-methoxy-2-naphthamide;

(7R,7aS)-3,3,7-trimethyltetrahydropyrrolo[1,2-c]oxazol-5(3H)-one;

(7R,7aS)-7-ethyl-3,3-dimethyltetrahydropyrrolo[1,2-c]oxazol-5(3H)-one;

(7S,7aS)-3,3-dimethyl-7-vinyltetrahydropyrrolo[1,2-c]oxazol-5(3H)-one;

(7S,7aS)-7-cyclopropyl-3,3-dimethyltetrahydropyrrolo[1,2-c]oxazol 5(3H)-one;

(6R,7S,7aS)-6-fluoro-3,3,7-trimethyltetrahydropyrrolo[1,2-c]oxazol-5(3H)-one;

(6S,7S,7aS)-6-fluoro-3,3,7-trimethyltetrahydropyrrolo[1,2-c]oxazol-5(3H)-one;

(6S,7S,7aS)-7-ethyl-6-fluoro-3,3-dimethyltetrahydropyrrolo[1,2-c]oxazol-5(3H)-one;

(6R,7S,7aS)-7-ethyl-6-fluoro-3,3-dimethyltetrahydropyrrolo[1,2-c]oxazol-5(3H)-one;

(7S,7aS)-7-ethyl-6-hydroxy-3,3-dimethyltetrahydropyrrolo[1,2-c]oxazol-5(3H)-one;

(3S,4S,5S)-3-fluoro-5-(hydroxymethyl)-4-methylpyrrolidin-2-one;

(4R,5S)-4-ethyl-5-(hydroxymethyl)pyrrolidin-2-one;

(1R,4S,5S,6S)-4-(hydroxymethyl)-6-methyl-3-azabicyclo[3.1.0]hexan-2-one;

(3S,4S,5S)-4-ethyl-3-fluoro-5-(hydroxymethyl)pyrrolidin-2-one;

(4R,5S)-3-fluoro-5-(hydroxymethyl)-4-(methoxymethyl)pyrrolidin-2-one;

(4S,5S)-3-(benzyloxy)-4-ethyl-5-(hydroxymethyl)pyrrolidin-2-one;

(4S,5S)-4-(2-fluoroethyl)-5-(hydroxymethyl)pyrrolidin-2-one;

(3S,4R,5S)-3-fluoro-4-(fluoromethyl)-5-(hydroxymethyl)pyrrolidin-2-one;

(3S,4S,5S)-3-fluoro-4-(2-fluoroethyl)-5-(hydroxymethyl)pyrrolidin-2-one; or

(3R,4R,5S)-3-fluoro-4-(fluoromethyl)-5-(hydroxymethyl)pyrrolidin-2-one

or pharmaceutically acceptable salts thereof or tautomers of said compounds or salt.

19. The compound, 4-{[(2S,3S,4S)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-6-methoxyquinazoline-7-carboxamide, or a pharmaceutically acceptable salt thereof or tautomer of said compound or salt.

20. 4-{[(2S,3S,4S)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-6-methoxyquinazoline-7-carboxamide or a pharmaceutically acceptable salt thereof.

21. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof or a tautomer of said compound or said salt and a pharmaceutically acceptable vehicle, diluents or carrier.

22. A pharmaceutical combination comprising a therapeutically effective amount of a composition comprising:

a first compound, the first compound being a compound of claim 1 or a pharmaceutically acceptable salt thereof or a tautomer of said compound or said salt;

a second compound, the second compound being selected from an approved drug or a clinical candidate useful for the treatment of systemic lupus erthematosus (SLE), lupus nephritis, rheumatoid arthritis, psoriasis, atopic dermatitis, gout, cryopyrin-associated periodic syndrome (CAPS), diffuse large B cell lymphoma (DLBCL), chronic kidney disease or acute kidney injury, chronic obstructive pulmonary disorder (COPD), asthma or bronchospasm; and

an optional pharmaceutically acceptable carrier, vehicle or diluent.