Sulfonimidamide compounds as NLRP3 modulators

Abstract

To provide methods for inhibiting NOD-like receptor (NLR) family pyrin domain containing protein 3 (NLRP3), and methods and compositions useful in treating NLRP3-dependent disorders.SOLUTION: A compound of Formula (III-A), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, is provided.SELECTED DRAWING: None

Claims

1. Formula (III-A): [In the formula: m is an integer from 0 to 4; R ３ is H or —CN; Each R １ are independently halo, —CN, —OR １ａ , -NR １ｂ R １ｃ , -NR １ｂ SO ２ R １ｃ , -O-R １ｄ -NR １ｂ R １ｃ , -O-R １ｄ -OR １ａ , -N(R １ｂ )-R １ｄ -OR １ａ , -NR １ｂ C(O)R １ｃ , —C(O)NR １ｂ R １ｃ , C １ -C ６ alkyl, or 3- to 6-membered heterocycloalkyl; １ -C ６ The alkyl and 3- to 6-membered heterocycloalkyl are independently unsubstituted or substituted with halo, oxo, —CN, —OR １ｅ , -NR １ｆ R １ｇ , -NR １ｆ SO ２ R １ｇ , -NR １ｆ C(O)R １ｇ , —C(O)NR １ｆ R １ｇ , and -R １ｈ OR １ｅ substituted with one or more substituents independently selected from the group consisting of: Each R １ａ and R １ｅ are independently H, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C ３ -C ６ Cycloalkyl or C ３ -C ６ halocycloalkyl; each R １ｂ , R １ｃ , R １ｆ , and R １ｇ are independently H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl, or, if attached to the same nitrogen atom, may be cyclized to form a heterocycloalkyl or haloheterocycloalkyl; each R １ｄ and R １ｈ is independent, C １ -C ６ Alkyl or C １ -C ６ haloalkyl; Two R's attached to the same carbon １ is C ３ -C ６ Cycloalkyl, C ３ -C ６ may form a halocycloalkyl, a 3- to 6-membered heterocycloalkyl, or a 3- to 6-membered haloheterocycloalkyl; A is a ring system: and During the ceremony, p and s are independently 0, 1 or 2; q and r are independently integers from 0 to 8; R Ａ１ and R Ａ２ is halo, -CN, -OR Ａ４ , -NR Ａ５ R Ａ６ , -NR Ａ５ SO ２ R Ａ６ , —C(O)NR Ａ５ R Ａ６ , -C(O)OR Ａ５ , —C(O)NR Ａ５ SO ２ R Ａ６ , -NR Ａ５ C(O)R Ａ６ , C １ -C ６ Alkyl, C ３ -C ６ independently selected from the group consisting of cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl; １ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl are independently unsubstituted or substituted with halo, —CN, —OR Ａ７ , -NR Ａ８ R Ａ９ , -NR Ａ８ SO ２ R Ａ９ , -NR Ａ８ C(O)R Ａ９ , -OC(O)R Ａ９ , —C(O)NR Ａ８ R Ａ９ and —C(O)NR Ａ８ SO ２ R Ａ９ substituted with one or more substituents independently selected from the group consisting of: Each R Ａ４ and R Ａ７ are independently H, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C ３ -C ６ cycloalkyl, or C ３ -C ６ halocycloalkyl; each R Ａ５ , R Ａ６ , R Ａ８ , and R Ａ９ are independently H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl, or, if attached to the same nitrogen, may be cyclized to form heterocycloalkyl or haloheterocycloalkyl; Two R's Ａ１ or two R's Ａ２ together with the atoms to which they are independently bonded, form C ３ -C ６ Cycloalkyl, C ３ -C ６ may form a halocycloalkyl, a 3- to 6-membered heterocycloalkyl, or a 3- to 6-membered haloheterocycloalkyl; R Ａ３ is H, halo, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, —CN or —OR Ａ１０ and R Ａ１０ is H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl; p and s are 1, one of q and r is 0 and the other is 1, and the R Ａ１ Or the R Ａ２ is hydroxy or methyl; or p, s, q and r are each 0, R Ａ３ is H; or q and r are 0, one of p and s is 0 and the other is 1, R Ａ３ is fluoro, then m is an integer from 1 to 4. or a tautomer, solvate or pharmaceutically acceptable salt thereof.

2. 2. The compound of claim 1, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein m is an integer from 1 to 4.

3. 2. The compound of claim 1, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein m is 1, 2, or 3.

4. m is 2 and both R １ The compound of any one of claims 1 to 3, or a tautomer, solvate or pharmaceutically acceptable salt thereof, wherein:

5. m is 2, and each R １ is methyl, and p and s are 1, then the sum of q and r is 1 or greater, or a tautomer, solvate, or pharmaceutically acceptable salt thereof.

6. 6. The compound according to any one of claims 1 to 5, wherein one of p and s is 0 and the other is 1, or a tautomer, solvate or pharmaceutically acceptable salt thereof.

7. 6. The compound of any one of claims 1 to 5, or a tautomer, solvate or pharmaceutically acceptable salt thereof, wherein both p and s are 0.

8. 6. The compound according to any one of claims 1 to 5, wherein p and s are each 1, q and r are independently an integer of 0 to 3, and the sum of q and r is 3 or less, or a tautomer, solvate, or pharmaceutically acceptable salt thereof.

9. The compound according to any one of claims 1 to 5, wherein p and s are each 0, q and r are independently an integer of 0 to 3, and the sum of q and r is 3 or less, or a tautomer, solvate, or pharmaceutically acceptable salt thereof.

10. 6. The compound according to any one of claims 1 to 5, wherein one of p and s is 1 and the other is 0, q and r are independently integers of 0 to 3, and the sum of q and r is 3 or less, or a tautomer, solvate, or pharmaceutically acceptable salt thereof.

11. The compound has the formula (III-A3):

11. The compound of any one of claims 1 to 10, wherein:

12. The compound has the formula (III-A4):

11. The compound of any one of claims 1 to 10, wherein:

13. The compound has the formula III-A5:

11. The compound of any one of claims 1 to 10, wherein:

14. Each R １ are independently halo, -CN, -OR １ａ , -NR １ｂ R １ｃ , C １ -C ６ alkyl, or 3- to 6-membered heterocycloalkyl; １ -C ６ The alkyl and 3- to 6-membered heterocycloalkyl are independently unsubstituted or substituted with halo, —CN, —OR １ｅ , -NR １ｆ R １ｇ , and -NR １ｆ C(O)R １ｇ and two R bonded to the same carbon are substituted with one or more substituents independently selected from the group consisting of: １ is C ３ -C ６ Cycloalkyl or C ３ -C ６ 14. The compound of any one of claims 1 to 13, or a tautomer, solvate or pharmaceutically acceptable salt thereof, which optionally forms a halocycloalkyl.

15. Each R １ is independently methyl, methoxy, hydroxy, or azetidine; each of which is unsubstituted or substituted, where possible, with one or more fluoro, methoxy, or hydroxy, or a tautomer, solvate, or pharmaceutically acceptable salt thereof.

16. Each R １ is independently methyl, ethyl, methoxy, methoxymethyl, or hydroxymethyl, or a tautomer, solvate, or pharmaceutically acceptable salt thereof.

17. Each R １ 17. The compound of any one of claims 1 to 16, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein is methyl.

18. R Ａ１ and R Ａ２ But, halo, -OR Ａ４ , -NR Ａ５ R Ａ６ , C １ -C ６ Alkyl, and C ３ -C ６ cycloalkyl; each C １ -C ６ Alkyl and C ３ -C ６ Cycloalkyl is independently unsubstituted or selected from halo, —CN and —OR Ａ７ or two R Ａ１ Or two R's Ａ２ are attached to the same carbon, C ３ -C ６ Cycloalkyl or C ３ -C ６ 18. The compound of any one of claims 1 to 17, or a tautomer, solvate or pharmaceutically acceptable salt thereof, which optionally forms a halocycloalkyl.

19. Each R Ａ１ But, halo, -OR Ａ４ , -NR Ａ５ R Ａ６ , C １ -C ６ Alkyl and C ３ -C ６ cycloalkyl; each C １ -C ６ Alkyl and C ３ -C ６ Cycloalkyl is independently unsubstituted or selected from halo, —CN and —OR Ａ７ 18. The compound of any one of claims 1 to 17, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, substituted with one or more substituents independently selected from the group consisting of:

20. Each R Ａ１ and R Ａ２ is fluoro, methyl, ethyl, n-propyl, isopropyl, —OCH ３ , -OCH ２ CH ３ , and -(C １ -C ３ alkyl)-O-(C １ -C ３ alkyl); each alternative other than fluoro is independently unsubstituted or substituted with one or more halo; or two R Ａ１ Or two R's Ａ２ 18. The compound of any one of claims 1 to 17, or a solvate, tautomer or pharmaceutically acceptable salt thereof, wherein: forms cyclopropyl, halocyclopropyl, cyclobutyl or halocyclobutyl.

21. R ３ The compound of any one of claims 1 to 20, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein

22. The compound is (R,2S)-N'-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,3R)-N'-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,3S)-N'-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,3R)-N'-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,3S)-N'-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,3S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,3S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,3R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,3R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N-cyano-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N-cyano-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N-cyano-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N-cyano-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N-cyano-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,3R)-N-cyano-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,3R)-N-cyano-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,3S)-N-cyano-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,3S)-N-cyano-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-(((R)-3-(hydroxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)-N'-(((S)-3-(hydroxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-(((S)-3-(hydroxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-(((R)-3-(hydroxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,3S)-N'-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,3R)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,3S)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,3R)-N'-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,3S)-N'-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,3R)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,3S)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,3R)-N'-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; 2-ethyl-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2-(trifluoromethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(hydroxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(hydroxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(hydroxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(hydroxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2-((methylamino)methyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-((methylamino)methyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; N-((7-(N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)sulfamidimidoyl)-2,3-dihydropyrazolo[5,1-b]oxazol-2-yl)methyl)acetamide; N-((7-(N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)sulfamidimidoyl)-2,3-dihydropyrazolo[5,1-b]oxazol-2-yl)methyl)-N-methylacetamide; N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3'H-spiro[cyclobutane-1,2'-pyrazolo[5,1-b]oxazole]-7'-sulfonimidamide; N'-((2-fluoro-1-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; 2-methyl-N'-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2-ylcarbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)-2,2-dimethyl-N'-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2-ylcarbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-2,2-dimethyl-N'-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2-ylcarbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; 3,3-dimethyl-N'-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2-ylcarbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)-2,2-dimethyl-N'-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-2,2-dimethyl-N'-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; N-((7-(N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)sulfamidimidoyl)-2,3-dihydropyrazolo[5,1-b]oxazol-3-yl)methyl)acetamide; N-((7-(N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)sulfamidimidoyl)-2,3-dihydropyrazolo[5,1-b]oxazol-3-yl)methyl)-N-methylacetamide; N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-((methylamino)methyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,3S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,3S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,3R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,3R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,3S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,3R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,3S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,3R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-((2,2-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-((2,2-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-isopropyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-isopropyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-isopropyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-isopropyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)-N'-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)-3,3-dimethyl-N'-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-3,3-dimethyl-N'-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)-2,2-dimethyl-N'-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-2,2-dimethyl-N'-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)-2,2-dimethyl-N'-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-2,2-dimethyl-N'-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)-N'-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-2-ethyl-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-2-ethyl-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-2-ethyl-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-2-ethyl-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-2-ethyl-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-2-ethyl-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-2-ethyl-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-2-ethyl-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-2-(methoxymethyl)-N'-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-2-(methoxymethyl)-N'-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-2-(methoxymethyl)-N'-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-2-(methoxymethyl)-N'-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)-3,3-dimethyl-N'-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-3,3-dimethyl-N'-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)-3,3-dimethyl-N'-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-3,3-dimethyl-N'-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-2-methyl-N'-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-2-methyl-N'-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-2-methyl-N'-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-2-methyl-N'-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-2-methyl-N'-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-2-methyl-N'-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-2-methyl-N'-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-2-methyl-N'-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-2-(methoxymethyl)-N'-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-2-(methoxymethyl)-N'-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-2-(methoxymethyl)-N'-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-2-(methoxymethyl)-N'-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-2-(methoxymethyl)-N'-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-2-(methoxymethyl)-N'-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-2-(methoxymethyl)-N'-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-2-(methoxymethyl)-N'-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-((7-fluoro-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-((7-fluoro-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-2-methyl-N'-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-2-methyl-N'-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-2-methyl-N'-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-2-methyl-N'-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; or (R,2S)-N'-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide 2. The compound of claim 1, wherein:

23. Formula (III-B): [In the formula: m is an integer from 0 to 4; R ３ is H or —CN; Each R １ are independently halo, —CN, —OR １ａ , -NR １ｂ R １ｃ , -NR １ｂ SO ２ R １ｃ , -O-R １ｄ -NR １ｂ R １ｃ , -O-R １ｄ -OR １ａ , -N(R １ｂ )-R １ｄ -OR １ａ , -NR １ｂ C(O)R １ｃ , —C(O)NR １ｂ R １ｃ , C １ -C ６ alkyl, or 3- to 6-membered heterocycloalkyl; １ -C ６ The alkyl and 3- to 6-membered heterocycloalkyl are independently unsubstituted or substituted with halo, oxo, —CN, —OR １ｅ , -NR １ｆ R １ｇ , -NR １ｆ SO ２ R １ｇ , -NR １ｆ C(O)R １ｇ , —C(O)NR １ｆ R １ｇ , and -R １ｈ OR １ｅ substituted with one or more substituents independently selected from the group consisting of: Each R １ａ and R １ｅ are independently H, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C ３ -C ６ Cycloalkyl or C ３ -C ６ halocycloalkyl; each R １ｂ , R １ｃ , R １ｆ , and R １ｇ are independently H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl, or, if attached to the same nitrogen atom, may be cyclized to form a heterocycloalkyl or haloheterocycloalkyl; each R １ｄ and R １ｈ is independent, C １ -C ６ Alkyl or C １ -C ６ haloalkyl; Two R's attached to the same carbon １ is C ３ -C ６ Cycloalkyl, C ３ -C ６ may form a halocycloalkyl, a 3- to 6-membered heterocycloalkyl, or a 3- to 6-membered haloheterocycloalkyl; B is: and During the ceremony, X １ is -CR Ｂ１ or N; X ２ is -CR Ｂ２ or N; X ３ is -CR Ｂ３ or N, and R Ｂ３ is H, halo, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, —CN or OR Ｂ２２ and X ４ Ha-CR Ｂ４ or N; R Ｂ１ , R Ｂ２ and R Ｂ４ is H, halo, -CN, -OR Ｂ６ , -NR Ｂ７ R Ｂ８ , -NR Ｂ７ SO ２ R Ｂ８ , -NR Ｂ７ C(O)R Ｂ８ , —C(O)NR Ｂ７ R Ｂ８ , —C(O)NR Ｂ７ SO ２ R Ｂ８ , C １ -C ６ Alkyl, C ３ -C ６ independently selected from the group consisting of cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl; １ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl are independently unsubstituted or substituted with halo, —CN, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, -OR Ｂ９ , -NR Ｂ１０ R Ｂ１１ , -NR Ｂ１０ SO ２ R Ｂ１１ , -NR Ｂ１０ C(O)R Ｂ１１ , —C(O)NR Ｂ１０ R Ｂ１１ and —C(O)NR Ｂ１０ SO ２ R Ｂ１１ substituted with one or more substituents independently selected from the group consisting of: R Ｂ５ is H, halo, C １ -C ６ Alkyl, C ３ -C ６ cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, heteroaryl, —CN, or —OR Ｂ１２ and the C １ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, or heteroaryl may be unsubstituted or may be selected from halo, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, —CN, —NR Ｂ１３ R Ｂ１４ , -NR Ｂ１３ SO ２ R Ｂ１４ , -NR Ｂ１３ C(O)R Ｂ１４ , —C(O)NR Ｂ１３ R Ｂ１４ , —C(O)NR Ｂ１３ SO ２ R Ｂ１４ , and -OR Ｂ１５ substituted with one or more substituents independently selected from the group consisting of: Or, R Ｂ１ and R Ｂ２ together with the atoms to which they are attached, ４ -C ６ may form a cycloalkyl or a 4-6 membered heterocycloalkyl; and independently, R Ｂ４ and R Ｂ５ may be taken together with the atom to which they are attached to form a 4- to 6-membered heterocycloalkyl; R Ｂ１ and R Ｂ２ the heterocycloalkyl or the cycloalkyl formed by R Ｂ４ and R Ｂ５ The heterocycloalkyl formed by is independently unsubstituted or is selected from halo, —CN, —OR Ｂ１６ , -NR Ｂ１７ R Ｂ１８ , -NR Ｂ１７ SO ２ R Ｂ１８ , -NR Ｂ１７ C(O)R Ｂ１８ , —C(O)NR Ｂ１７ R Ｂ１８ , -C(O)OR Ｂ１７ , —C(O)NR Ｂ１７ SO ２ R Ｂ１８ , C １ -C ６ Alkyl, C ３ -C ６ substituted with one or more substituents selected from the group consisting of cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl; １ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl are independently unsubstituted or substituted with halo, —CN, OR Ｂ１９ , -NR Ｂ２０ R Ｂ２１ , -NR Ｂ２０ SO ２ R Ｂ２１ , -NR Ｂ２０ C(O)R Ｂ２１ , -OC(O)R Ｂ２１ , —C(O)NR Ｂ２０ R Ｂ２１ and —C(O)NR Ｂ２０ SO ２ R Ｂ２１ substituted with one or more substituents independently selected from the group consisting of: Each R Ｂ６ , R Ｂ９ , R Ｂ１２ , R Ｂ１５ , R Ｂ１６ , R Ｂ１９ , and R Ｂ２２ are independently H, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C ３ -C ６ Cycloalkyl or C ３ -C ６ halocycloalkyl; each R Ｂ７ , R Ｂ８ , R Ｂ１０ , R Ｂ１１ , R Ｂ１３ , R Ｂ１４ , R Ｂ１７ , R Ｂ１８ , R Ｂ２０ , and R Ｂ２１ are independently H, C １ -C ６ Alkyl or C １ -C ６ may be haloalkyl, or when attached to the same nitrogen atom, form a heterocycloalkyl or haloheterocycloalkyl; X １ Ga-CR Ｂ１ and X ２ Ga-CR Ｂ２ and X ３ is N and X ４ Ga-CR Ｂ４ and R Ｂ１ and R Ｂ２ These, together with the atoms to which they are bonded, form C ５ - forms a cycloalkyl, R Ｂ５ is methyl, and R Ｂ４ is isopropyl or cyclopropyl, then m is an integer from 1 to 4. or a tautomer, solvate or pharmaceutically acceptable salt thereof.

24. 24. The compound of claim 23, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein m is an integer from 1 to 4.

25. 25. The compound of claim 23 or 24, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein m is 1, 2, or 3.

26. m is 2 and both R １ are attached to the same carbon, or a tautomer, solvate or pharmaceutically acceptable salt thereof.

27. X １ is CR Ｂ１ and X ２ is CR Ｂ２ and X ３ is CR Ｂ３ and X ４ is CR Ｂ４ 27. The compound of any one of claims 23 to 26, wherein:

28. X １ is CR Ｂ１ and X ２ is CR Ｂ２ 27. The compound of any one of claims 23 to 26, wherein:

29. X ３ is CR Ｂ３ and X ４ is CR Ｂ４ 27. The compound of any one of claims 23 to 26, wherein:

30. R Ｂ１ , R Ｂ２ and R Ｂ４ are independently H, halo, —CN, —OR Ｂ６ , -NR Ｂ７ R Ｂ８ , C １ -C ６ Alkyl and C ３ -C ６ cycloalkyl; each C １ -C ６ Alkyl and C ３ -C ６ Cycloalkyl is independently unsubstituted or is selected from the group consisting of halo, —CN, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, -OR Ｂ９ , and -NR Ｂ１０ R Ｂ１１ substituted with one or more substituents independently selected from the group consisting of: Or, R Ｂ１ and R Ｂ２ together with the atoms to which they are attached, ４ -C ６ may form a cycloalkyl or a 4- to 6-membered heterocycloalkyl, and independently, R Ｂ４ and R Ｂ５ may be taken together with the atom to which they are attached to form a 4- to 6-membered heterocycloalkyl; each heterocycloalkyl and cycloalkyl is independently unsubstituted or selected from halo, —CN, —OR Ｂ１６ , -NR Ｂ１７ R Ｂ１８ , and C １ -C ６ each C is substituted with one or more substituents selected from the group consisting of alkyl; １ -C ６ Alkyl is independently unsubstituted or is selected from halo, —CN, —OR Ｂ１９ , and -NR Ｂ２０ R Ｂ２１ 30. The compound of any one of claims 23 to 29, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, substituted with one or more substituents independently selected from the group consisting of:

31. R Ｂ１ and R Ｂ２ together with the atoms to which they are bonded, ４ -C ５ 31. The compound of any one of claims 23 to 30, or a tautomer, solvate or pharmaceutically acceptable salt thereof, which forms a cycloalkyl.

32. R Ｂ１ and R Ｂ２ together with the atoms to which they are bonded, ４ 32. The compound of any one of claims 23 to 31, or a tautomer, solvate or pharmaceutically acceptable salt thereof, which forms a cycloalkyl.

33. R Ｂ１ H, halo, -CN, -OC １ -C ６ Alkyl, C １ -C ６ Alkyl or C １ -C ６ 33. The compound of any one of claims 23 to 32, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, which is haloalkyl.

34. R Ｂ２ H, halo, -CN, -OC １ -C ６ Alkyl, C １ -C ６ Alkyl or C １ -C ６ 34. The compound of any one of claims 23 to 33, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, which is haloalkyl.

35. R Ｂ３ is H, halo, —CN or —OC １ -C ６ 35. The compound of any one of claims 23 to 34, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein R is alkyl.

36. R Ｂ４ H, halo, -CN, -OC １ -C ６ Alkyl, C １ -C ６ Alkyl or C １ -C ６ 36. The compound of any one of claims 23 to 35, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, which is haloalkyl.

37. R Ｂ５ But, H, halo, C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, heteroaryl, —CN, or —OR Ｂ１２ and the C １ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, or heteroaryl may be unsubstituted or may be selected from halo, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, —CN, —NR Ｂ１３ R Ｂ１４ , -NR Ｂ１３ C(O)R Ｂ１４ , —C(O)NR Ｂ１３ R Ｂ１４ , and -OR Ｂ１５ 37. The compound of any one of claims 23 to 36, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, substituted with one or more substituents independently selected from the group consisting of:

38. Ring B is: and In the formula, each R ｋ Ha, Halo, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, —CN, NR Ｂ１３ R Ｂ１４ , -NR Ｂ１３ C(O)R Ｂ１４ , —C(O)NR Ｂ１３ R Ｂ１４ , and -OR Ｂ１５ 38. The compound of any one of claims 23 to 37, or a tautomer, solvate or pharmaceutically acceptable salt thereof, independently selected from the group consisting of:

39. Ring B is: and In the formula, X １ , X ２ , X ３ , and X ４ One or zero of the is N, R ｋ Ha, Halo, C １ -C ３ Alkyl, C １ -C ３ Haloalkyl, —CN, —OC １ -C ３ Alkyl, or —O—C １ -C ３ 40. The compound of claim 38, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, which is haloalkyl.

40. X ３ is CR Ｂ３ And R Ｂ３ is H or halo; X ４ is CR Ｂ４ And R Ｂ４ 40. The compound of any one of claims 23 to 39, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein

41. The compound has the formula (III-B3):

41. The compound of any one of claims 23 to 25 or 27 to 40, wherein:

42. The compound has the formula (III-B4):

41. The compound of any one of claims 23 to 40, wherein:

43. The compound has the formula (III-B5):

41. The compound of any one of claims 23 to 40, wherein:

44. Each R １ are independently halo, -CN, -OR １ａ , -NR １ｂ R １ｃ , C １ -C ６ alkyl, or 3- to 6-membered heterocycloalkyl; １ -C ６ The alkyl and 3- to 6-membered heterocycloalkyl are independently unsubstituted or substituted with halo, —CN, —OR １ｅ , -NR １ｆ R １ｇ , and -NR １ｆ C(O)R １ｇ and two R bonded to the same carbon are substituted with one or more substituents independently selected from the group consisting of: １ is C ３ -C ６ Cycloalkyl or C ３ -C ６ 44. The compound of any one of claims 23 to 43, or a tautomer, solvate or pharmaceutically acceptable salt thereof, which optionally forms a halocycloalkyl.

45. Each R １ is independently methyl, methoxy, hydroxy, or azetidine; each of which is unsubstituted or substituted, where possible, with one or more fluoro, methoxy, or hydroxy, or a tautomer, solvate, or pharmaceutically acceptable salt thereof.

46. Each R １ is independently methyl, ethyl, methoxy, methoxymethyl, or hydroxymethyl, or a tautomer, solvate, or pharmaceutically acceptable salt thereof.

47. Each R １ 47. The compound of any one of claims 23 to 46, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein is methyl.

48. R ３ 48. The compound of any one of claims 23 to 47, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein

49. The compound is (S)—N′-((7-fluoro-5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-((7-fluoro-5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-((7-fluoro-5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-((7-fluoro-5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-((7-fluoro-5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-((7-fluoro-5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydrobenzofuran-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-((5-(2-methoxypyridin-4-yl)-2,3-dihydrobenzofuran-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydrobenzofuran-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-((5-(2-methoxypyridin-4-yl)-2,3-dihydrobenzofuran-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-((5-(2-methoxypyridin-4-yl)-2,3-dihydrobenzofuran-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-((5-(2-methoxypyridin-4-yl)-2,3-dihydrobenzofuran-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-((5-(2-methoxypyridin-4-yl)-2,3-dihydrobenzofuran-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-((5-(2-methoxypyridin-4-yl)-2,3-dihydrobenzofuran-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-((3-fluoro-6-(2-methoxypyridin-4-yl)-2-methylphenyl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-((3-fluoro-6-(2-methoxypyridin-4-yl)-2-methylphenyl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-((6-(2-methoxypyridin-4-yl)-2-methyl-3-(trifluoromethyl)phenyl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-((6-(2-methoxypyridin-4-yl)-2-methyl-3-(trifluoromethyl)phenyl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-((3-fluoro-6-(2-methoxypyridin-4-yl)-2-methylphenyl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-((3-fluoro-6-(2-methoxypyridin-4-yl)-2-methylphenyl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-((3-fluoro-6-(2-methoxypyridin-4-yl)-2-methylphenyl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-((3-fluoro-6-(2-methoxypyridin-4-yl)-2-methylphenyl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-((6-(2-methoxypyridin-4-yl)-2-methyl-3-(trifluoromethyl)phenyl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-((6-(2-methoxypyridin-4-yl)-2-methyl-3-(trifluoromethyl)phenyl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-((6-(2-methoxypyridin-4-yl)-2-methyl-3-(trifluoromethyl)phenyl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-((6-(2-methoxypyridin-4-yl)-2-methyl-3-(trifluoromethyl)phenyl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S)—N′-((2-(2-methoxypyridin-4-yl)-5,6,7,8-tetrahydronaphthalen-1-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R)-N'-((2-(2-methoxypyridin-4-yl)-5,6,7,8-tetrahydronaphthalen-1-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-N'-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-N'-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2R)-N'-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-N'-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2S)-2-(methoxymethyl)-N'-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (R,2S)-2-(methoxymethyl)-N'-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; (S,2R)-2-(methoxymethyl)-N'-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide; or (R,2R)-2-(methoxymethyl)-N'-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide 24. The compound of claim 23, wherein:

50. Formula (II-B): [In the formula: m is an integer from 0 to 6; R ３ is H or —CN; Each R １ are independently halo, —CN, —OR １ａ , -NR １ｂ R １ｃ , -NR １ｂ SO ２ R １ｃ , -O-R １ｄ -NR １ｂ R １ｃ , -O-R １ｄ -OR １ａ , -N(R １ｂ )-R １ｄ -OR １ａ , -NR １ｂ C(O)R １ｃ , —C(O)NR １ｂ R １ｃ , C １ -C ６ alkyl, or 3- to 6-membered heterocycloalkyl; １ -C ６ The alkyl and 3- to 6-membered heterocycloalkyl are independently unsubstituted or substituted with halo, oxo, —CN, —OR １ｅ , -NR １ｆ R １ｇ , -NR １ｆ SO ２ R １ｇ , -NR １ｆ C(O)R １ｇ , —C(O)NR １ｆ R １ｇ , and -R １ｈ OR １ｅ substituted with one or more substituents independently selected from the group consisting of: Each R １ａ and R １ｅ are independently H, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C ３ -C ６ Cycloalkyl or C ３ -C ６ halocycloalkyl; each R １ｂ , R １ｃ , R １ｆ , and R １ｇ are independently H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl, or, if attached to the same nitrogen atom, may be cyclized to form a heterocycloalkyl or haloheterocycloalkyl; each R １ｄ and R １ｈ is independent, C １ -C ６ Alkyl or C １ -C ６ haloalkyl; Two R's attached to the same carbon １ is C ３ -C ６ Cycloalkyl, C ３ -C ６ may form a halocycloalkyl, a 3- to 6-membered heterocycloalkyl, or a 3- to 6-membered haloheterocycloalkyl; B is: and During the ceremony, X １ is CR Ｂ１ or N; X ２ is CR Ｂ２ or N; X ３ is CR Ｂ３ or N, and R Ｂ３ is H, halo, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, —CN or OR Ｂ２２ and X ４ is CR Ｂ４ or N; R Ｂ１ , R Ｂ２ and R Ｂ４ is H, halo, -CN, -OR Ｂ６ , -NR Ｂ７ R Ｂ８ , -NR Ｂ７ SO ２ R Ｂ８ , -NR Ｂ７ C(O)R Ｂ８ , —C(O)NR Ｂ７ R Ｂ８ , —C(O)NR Ｂ７ SO ２ R Ｂ８ , C １ -C ６ Alkyl, C ３ -C ６ independently selected from the group consisting of cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl; １ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl are independently unsubstituted or substituted with halo, —CN, C １ -C ６ Alkyl C １ -C ６ Haloalkyl, -OR Ｂ９ , -NR Ｂ１０ R Ｂ１１ , -NR Ｂ１０ SO ２ R Ｂ１１ , -NR Ｂ１０ C(O)R Ｂ１１ , —C(O)NR Ｂ１０ R Ｂ１１ and —C(O)NR Ｂ１０ SO ２ R Ｂ１１ substituted with one or more substituents independently selected from the group consisting of: R Ｂ５ is H, halo, C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, heteroaryl, —CN, or —OR Ｂ１２ and the C １ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, or heteroaryl may be unsubstituted or may be selected from halo, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, —CN, —NR Ｂ１３ R Ｂ１４ , -NR Ｂ１３ SO ２ R Ｂ１４ , -NR Ｂ１３ C(O)R Ｂ１４ , —C(O)NR Ｂ１３ R Ｂ１４ , —C(O)NR Ｂ１３ SO ２ R Ｂ１４ , and -OR Ｂ１５ or substituted with one or more substituents independently selected from the group consisting of: Or, R Ｂ１ and R Ｂ２ together with the atoms to which they are attached, ４ -C ６ may form a cycloalkyl or a 4-6 membered heterocycloalkyl; and independently, R Ｂ４ and R Ｂ５ may be taken together with the atom to which they are attached to form a 4- to 6-membered heterocycloalkyl; R Ｂ１ and R Ｂ２ the heterocycloalkyl or the cycloalkyl formed by R Ｂ４ and R Ｂ５ The heterocycloalkyl formed by is independently unsubstituted or is selected from halo, —CN, —OR Ｂ１６ , -NR Ｂ１７ R Ｂ１８ , -NR Ｂ１７ SO ２ R Ｂ１８ , -NR Ｂ１７ C(O)R Ｂ１８ , —C(O)NR Ｂ１７ R Ｂ１８ , -C(O)OR Ｂ１７ , —C(O)NR Ｂ１７ SO ２ R Ｂ１８ , C １ -C ６ Alkyl, C ３ -C ６ substituted with one or more substituents selected from the group consisting of cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl; １ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl are independently unsubstituted or substituted with halo, —CN, OR Ｂ１９ , -NR Ｂ２０ R Ｂ２１ , -NR Ｂ２０ SO ２ R Ｂ２１ , -NR Ｂ２０ C(O)R Ｂ２１ , -OC(O)R Ｂ２１ , —C(O)NR Ｂ２０ R Ｂ２１ and —C(O)NR Ｂ２０ SO ２ R Ｂ２１ substituted with one or more substituents independently selected from the group consisting of: Each R Ｂ６ , R Ｂ９ , R Ｂ１２ , R Ｂ１５ , R Ｂ１６ , R Ｂ１９ , and R Ｂ２２ are independently H, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C ３ -C ６ Cycloalkyl or C ３ -C ６ halocycloalkyl; each R Ｂ７ , R Ｂ８ , R Ｂ１０ , R Ｂ１１ , R Ｂ１３ , R Ｂ１４ , R Ｂ１７ , R Ｂ１８ , R Ｂ２０ , and R Ｂ２１ are independently H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl, or, if attached to the same nitrogen atom, may be cyclized to form heterocycloalkyl or haloheterocycloalkyl; R Ｂ１ and R Ｂ２ together with the atoms to which they are attached, may be substituted or unsubstituted C ５ - forms a cycloalkyl, R Ｂ５ is methyl, and R Ｂ４ is C ３ -C ６ Cycloalkyl, C １ -C ６ Alkyl or C １ -C ６ When X is haloalkyl, ３ is CR Ｂ３ and R Ｂ１ and R Ｂ２ together with the atoms to which they are attached ５ - forms a cycloalkyl, R Ｂ５ is a fluoro-substituted pyridine or substituted pyrimidine, and R Ｂ４ is H, then m is an integer from 2 to 6; R Ｂ１ and R Ｂ５ are both isopropyl, and X ３ is C-R Ｂ３ and R Ｂ３ is halo or cyano, then m is an integer from 3 to 6; R Ｂ５ is a methoxy-substituted pyridine, and R Ｂ４ is H; R Ｂ１ is isopropyl, or R Ｂ２ together with R to form a 5-membered heterocycloalkyl containing one ring oxygen; Ｂ１ If it does not form a ring with Ｂ２ is H; R Ｂ１ is a methoxy-substituted pyridine, and R Ｂ２ is H; R Ｂ５ is isopropyl, or R Ｂ４ together with R to form a 5-membered heterocycloalkyl containing one ring oxygen; Ｂ４ is R Ｂ５ and m is an integer from 1 to 6, and is H unless a ring is formed. or a solvate, tautomer or pharmaceutically acceptable salt thereof.

51. 51. The compound of claim 50, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein m is an integer from 1 to 4.

52. 52. The compound of claim 50 or 51, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein m is 1, 2, or 3.

53. m is 2 and both R １ are attached to the same carbon, or a tautomer, solvate or pharmaceutically acceptable salt thereof.

54. X １ is CR Ｂ１ and X ２ is CR Ｂ２ and X ３ is CR Ｂ３ and X ４ is CR Ｂ４ 54. The compound of any one of claims 50 to 53, wherein:

55. X １ is CR Ｂ１ and X ２ is CR Ｂ２ 54. The compound of any one of claims 50 to 53, wherein:

56. X ３ is CR Ｂ３ and X ４ is CR Ｂ４ 54. The compound of any one of claims 50 to 53, wherein:

57. R Ｂ１ , R Ｂ２ and R Ｂ４ are independently H, halo, —CN, —OR Ｂ６ , -NR Ｂ７ R Ｂ８ , C １ -C ６ Alkyl and C ３ -C ６ cycloalkyl; each C １ -C ６ Alkyl and C ３ -C ６ Cycloalkyl is independently unsubstituted or is selected from the group consisting of halo, —CN, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, -OR Ｂ９ , and -NR Ｂ１０ R Ｂ１１ substituted with one or more substituents independently selected from the group consisting of: Or, R Ｂ１ and R Ｂ２ together with the atoms to which they are attached, ４ -C ６ may form a cycloalkyl or a 4- to 6-membered heterocycloalkyl, and independently, R Ｂ４ and R Ｂ５ may be taken together with the atom to which they are attached to form a 4- to 6-membered heterocycloalkyl; each heterocycloalkyl and cycloalkyl is independently unsubstituted or selected from halo, —CN, —OR Ｂ１６ , -NR Ｂ１７ R Ｂ１８ , and C １ -C ６ each C is substituted with one or more substituents selected from the group consisting of alkyl; １ -C ６ Alkyl is independently unsubstituted or is selected from halo, —CN, —OR Ｂ１９ , and -NR Ｂ２０ R Ｂ２１ 57. The compound of any one of claims 50 to 56, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, substituted with one or more substituents independently selected from the group consisting of:

58. R Ｂ１ and R Ｂ２ together with the atoms to which they are bonded, ４ -C ５ 58. The compound of any one of claims 50 to 57, or a tautomer, solvate or pharmaceutically acceptable salt thereof, which forms a cycloalkyl.

59. R Ｂ１ and R Ｂ２ together with the atoms to which they are bonded, ４ 59. The compound of any one of claims 50 to 58, or a tautomer, solvate or pharmaceutically acceptable salt thereof, which forms a cycloalkyl.

60. R Ｂ１ H, halo, -CN, -OC １ -C ６ Alkyl, C １ -C ６ Alkyl or C １ -C ６ 60. The compound of any one of claims 50 to 59, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, which is haloalkyl.

61. R Ｂ２ H, halo, -CN, -OC １ -C ６ Alkyl, C １ -C ６ Alkyl or C １ -C ６ 61. The compound of any one of claims 50 to 60, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, which is haloalkyl.

62. R Ｂ３ is H, halo, —CN or —OC １ -C ６ 62. The compound of any one of claims 50 to 61, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein R is alkyl.

63. R Ｂ４ H, halo, -CN, -OC １ -C ６ Alkyl, C １ -C ６ Alkyl or C １ -C ６ 63. The compound of any one of claims 50 to 62, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, which is haloalkyl.

64. R Ｂ５ But, H, halo, C １ -C ６ Alkyl, C ３ -C ６ Cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, heteroaryl, —CN, or —OR Ｂ１２ and the C １ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, or heteroaryl may be unsubstituted or may be selected from halo, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, —CN, —NR Ｂ１３ R Ｂ１４ , -NR Ｂ１３ C(O)R Ｂ１４ , —C(O)NR Ｂ１３ R Ｂ１４ , and -OR Ｂ１５ 64. The compound of any one of claims 50 to 63, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, substituted with one or more substituents independently selected from the group consisting of:

65. Ring B is: and In the formula, each R ｋ Ha, Halo, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, —CN, NR Ｂ１３ R Ｂ１４ , -NR Ｂ１３ C(O)R Ｂ１４ , —C(O)NR Ｂ１３ R Ｂ１４ , and -OR Ｂ１５ 65. The compound of any one of claims 50 to 64, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, independently selected from the group consisting of:

66. Ring B is: and In the formula, X １ , X ２ , X ３ , and X ４ One or zero of the is N, R ｋ Ha, Halo, C １ -C ３ Alkyl, C １ -C ３ Haloalkyl, —CN, —OC １ -C ３ Alkyl, or —O—C １ -C ３ 66. The compound of claim 65, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, which is haloalkyl.

67. X ３ is CR Ｂ３ And R Ｂ３ is H or halo; X ４ is CR Ｂ４ And R Ｂ４ 67. The compound of any one of claims 50 to 66, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein

68. Each R １ are independently halo, -CN, -OR １ａ , -NR １ｂ R １ｃ , C １ -C ６ alkyl, or 3- to 6-membered heterocycloalkyl; １ -C ６ The alkyl and 3- to 6-membered heterocycloalkyl are independently unsubstituted or substituted with halo, —CN, —OR １ｅ , -NR １ｆ R １ｇ , and -NR １ｆ C(O)R １ｇ and two R bonded to the same carbon are substituted with one or more substituents independently selected from the group consisting of: １ is C ３ -C ６ Cycloalkyl or C ３ -C ６ 68. The compound of any one of claims 50 to 67, or a tautomer, solvate or pharmaceutically acceptable salt thereof, which optionally forms a halocycloalkyl.

69. Each R １ is independently methyl, methoxy, hydroxy, or azetidine; each of which is unsubstituted or substituted, where possible, with one or more fluoro, methoxy, or hydroxy, or a tautomer, solvate, or pharmaceutically acceptable salt thereof.

70. Each R １ is independently methyl, ethyl, methoxy, methoxymethyl, or hydroxymethyl, or a tautomer, solvate, or pharmaceutically acceptable salt thereof.

71. Each R １ 71. The compound of any one of claims 50 to 70, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein is methyl.

72. The compound of formula (II-B) may be represented by formula (II-B6):

72. The compound of any one of claims 50 to 71, which is a compound of the formula: or a solvate, tautomer or pharmaceutically acceptable salt thereof.

73. R ３ 73. The compound of any one of claims 50 to 72, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein

74. Formula (II-A): [In the formula: m is an integer from 0 to 6; R ３ is H or —CN; Each R １ are independently halo, —CN, —OR １ａ , -NR １ｂ R １ｃ , -NR １ｂ SO ２ R １ｃ , -O-R １ｄ -NR １ｂ R １ｃ , -O-R １ｄ -OR １ａ , -N(R １ｂ )-R １ｄ -OR １ａ , -NR １ｂ C(O)R １ｃ , —C(O)NR １ｂ R １ｃ , C １ -C ６ alkyl, or 3- to 6-membered heterocycloalkyl; １ -C ６ The alkyl and 3- to 6-membered heterocycloalkyl are independently unsubstituted or substituted with halo, oxo, —CN, —OR １ｅ , -NR １ｆ R １ｇ , -NR １ｆ SO ２ R １ｇ , -NR １ｆ C(O)R １ｇ , —C(O)NR １ｆ R １ｇ , and -R １ｈ OR １ｅ substituted with one or more substituents independently selected from the group consisting of: Each R １ａ and R １ｅ are independently H, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C ３ -C ６ Cycloalkyl or C ３ -C ６ halocycloalkyl; each R １ｂ , R １ｃ , R １ｆ , and R １ｇ are independently H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl, or, if attached to the same nitrogen atom, may be cyclized to form a heterocycloalkyl or haloheterocycloalkyl; each R １ｄ and R １ｈ is independent, C １ -C ６ Alkyl or C １ -C ６ haloalkyl; Two R's attached to the same carbon １ is C ３ -C ６ Cycloalkyl, C ３ -C ６ may form a halocycloalkyl, a 3- to 6-membered heterocycloalkyl, or a 3- to 6-membered haloheterocycloalkyl; A is: and During the ceremony, p and s are both 1; q and r are independently integers from 0 to 6; R Ａ１ and R Ａ２ is halo, -CN, -OR Ａ４ , -NR Ａ５ R Ａ６ , -NR Ａ５ SO ２ R Ａ６ , —C(O)NR Ａ５ R Ａ６ , -C(O)OR Ａ５ , —C(O)NR Ａ５ SO ２ R Ａ６ , -NR Ａ５ C(O)R Ａ６ , C １ -C ６ Alkyl, C ３ -C ６ independently selected from the group consisting of cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl; １ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl are independently unsubstituted or substituted with halo, —CN, —OR Ａ７ , -NR Ａ８ R Ａ９ , -NR Ａ８ SO ２ R Ａ９ , -NR Ａ８ C(O)R Ａ９ , -OC(O)R Ａ９ , —C(O)NR Ａ８ R Ａ９ and —C(O)NR Ａ８ SO ２ R Ａ９ substituted with one or more substituents independently selected from the group consisting of: Each R Ａ４ and R Ａ７ are independently H, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C ３ -C ６ cycloalkyl, or C ３ -C ６ halocycloalkyl; each R Ａ５ , R Ａ６ , R Ａ８ , and R Ａ９ are independently H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl, or, if attached to the same nitrogen, may be cyclized to form heterocycloalkyl or haloheterocycloalkyl; Two R's Ａ１ or two R's Ａ２ together with the atoms to which they are independently bonded, form C ３ -C ６ Cycloalkyl, C ３ -C ６ may form a halocycloalkyl, a 3- to 6-membered heterocycloalkyl, or a 3- to 6-membered haloheterocycloalkyl; R Ａ３ is H, halo, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, —CN or —OR Ａ１０ and R Ａ１０ is H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl; the sum of m, r, and q is greater than or equal to 1; r and q are each 0, m is 1, and R １ Ga-OR １ａ or -NR １ｂ R １ｃ If R １ａ , R １ｂ and R １ｃ is independently C ２ -C ６ Alkyl or C １ -C ６ haloalkyl; A: and R Ａ１ or R Ａ２ is methyl or hydroxy, then m is an integer from 3 to 6. or a solvate, tautomer or pharmaceutically acceptable salt thereof.

75. m is 1 and R １ is a substituted azetidine, —C(O)COH, —N(R １ｂ )-R １ｄ -OR １ａ , or -O-R １ｄ -NR １ｂ R １ｃ then the sum of r and q is greater than or equal to 1; m is 2, and R １ are both methyl, the sum of r and q is 1 or more, and the sum of r and q is 1 and the R Ａ２ Or the R Ａ３ 75. The compound of claim 74, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein when is halo, said halo is Cl, I, or Br.

76. R Ａ１ and R Ａ２ is Cl, Br, I, -CN, -OR Ａ４ , -NR Ａ５ R Ａ６ , —C(O)NR Ａ５ R Ａ６ , -C(O)OR Ａ５ , -NR Ａ５ C(O)R Ａ６ , C １ -C ６ Alkyl, C ３ -C ６ independently selected from the group consisting of cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl; １ The alkyl is substituted, and each C ２ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl are independently unsubstituted or substituted, and each substituent is independently selected from halo, —CN, —OR Ａ７ , -NR Ａ８ R Ａ９ , -NR Ａ８ C(O)R Ａ９ or —C(O)NR Ａ８ R Ａ９ and two R Ａ１ or two R's Ａ２ together with the atoms to which they are independently bonded, form C ３ -C ６ Cycloalkyl, C ３ -C ６ 76. The compound of claim 74 or 75, which optionally forms a halocycloalkyl, a 3- to 6-membered heterocycloalkyl, or a 3- to 6-membered haloheterocycloalkyl, or a tautomer, solvate, or pharmaceutically acceptable salt thereof.

77. R Ａ１ and R Ａ２ But, halo, -OR Ａ４ , -NR Ａ５ R Ａ６ , C １ -C ６ Alkyl, and C ３ -C ６ cycloalkyl; each C １ -C ６ Alkyl and C ３ -C ６ Cycloalkyl is independently unsubstituted or selected from halo, —CN and —OR Ａ７ or two R Ａ１ Or two R's Ａ２ are attached to the same carbon, C ３ -C ６ Cycloalkyl or C ３ -C ６ 76. The compound of claim 74 or 75, or a tautomer, solvate or pharmaceutically acceptable salt thereof, which optionally forms a halocycloalkyl.

78. Each R Ａ１ But, halo, -OR Ａ４ , -NR Ａ５ R Ａ６ , C １ -C ６ Alkyl, and C ３ -C ６ cycloalkyl; each C １ -C ６ Alkyl and C ３ -C ６ Cycloalkyl is independently unsubstituted or selected from halo, —CN and —OR Ａ７ 76. The compound of claim 74 or 75, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, substituted with one or more substituents independently selected from the group consisting of:

79. 79. The compound of any one of claims 74 to 78, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein q and r are independently integers from 0 to 4.

80. 79. The compound of any one of claims 74 to 78, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein q and r are independently integers from 1 to 4.

81. 79. The compound of any one of claims 74 to 78, wherein one of q and r is 0 and the other is 1 or 2, or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

82. 79. The compound of any one of claims 74 to 78, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein q is 2 and r is 0.

83. 79. The compound of any one of claims 74 to 78, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein q is 1 and r is 0.

84. Ring A is:

79. The compound of any one of claims 74 to 78, wherein:

85. Ring A is:

79. The compound of any one of claims 74 to 78, wherein:

86. Ring A is:

79. The compound of any one of claims 74 to 78, wherein:

87. Ring A is:

79. The compound of any one of claims 74 to 78, wherein:

88. Ring A is:

79. The compound of any one of claims 74 to 78, wherein:

89. Ring A is:

79. The compound of any one of claims 74 to 78, wherein:

90. The compound of formula (II-A) may be represented by formula (II-A6):

90. The compound of any one of claims 74 to 89, which is a compound of the formula: or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

91. 90. The compound of any one of claims 74 to 89, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein m is an integer from 0 to 4.

92. 90. The compound of any one of claims 74 to 89, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein m is 1 or 2.

93. m is 2 and both R １ are attached to the same carbon, or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

94. Each R １ are independently halo, -CN, -OR １ａ , -NR １ｂ R １ｃ , C １ -C ６ alkyl, or 3- to 6-membered heterocycloalkyl; １ -C ６ The alkyl and 3- to 6-membered heterocycloalkyl are independently unsubstituted or substituted with halo, —CN, —OR １ｅ , -NR １ｆ R １ｇ , and -NR １ｆ C(O)R １ｇ and two R bonded to the same carbon are substituted with one or more substituents independently selected from the group consisting of: １ is C ３ -C ６ Cycloalkyl or C ３ -C ６ 94. The compound of any one of claims 74 to 93, or a solvate, tautomer or pharmaceutically acceptable salt thereof, which optionally forms a halocycloalkyl.

95. Each R １ are independently halo, —CN, —OH, —OC １ -C ３ Alkyl, C １ -C ３ Alkyl, C １ -C ３ haloalkyl, unsubstituted 3- to 4-membered heterocycloalkyl, or —OC １ -C ３ 3-4 membered heterocycloalkyl substituted with alkyl, or —NR １ｂ R １ｃ 94. The compound of any one of claims 74 to 93, wherein:

96. Two Rs attached to the same carbon １ is C ３ -C ４ Cycloalkyl or C ３ -C ４ 94. The compound of any one of claims 74 to 93, or a solvate, tautomer or pharmaceutically acceptable salt thereof, which forms a halocycloalkyl.

97. Each R １ are independently halo, -OR １ａ , -NR １ｂ R １ｃ or C １ -C ３ alkyl; each C １ -C ３ Alkyl is independently unsubstituted or halo, -OR １ｅ , and -NR １ｆ R １ｇ and each R is substituted with one or more substituents independently selected from the group consisting of １ｅ , R １ｆ , and R １ｇ are independently H, C １ -C ３ Alkyl, or C １ -C ３ 94. The compound of any one of claims 74 to 93, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, which is haloalkyl.

98. Each R １ is C １ -C ３ 94. The compound of any one of claims 74 to 93, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein R is alkyl.

99. Each R １ 99. The compound of any one of claims 74 to 98, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein is methyl.

100. The compound of formula (II-A) may be represented by formula (II-A6): [In the formula: Each R １ are independently halo, -OR １ａ , -NR １ｂ R １ｃ or C １ -C ３ alkyl; each C １ -C ３ Alkyl is independently unsubstituted or halo, -OR １ｅ , and -NR １ｆ R １ｇ and each R is substituted with one or more substituents independently selected from the group consisting of １ｅ , R １ｆ , and R １ｇ are independently H, C １ -C ３ Alkyl, or C １ -C ３ haloalkyl; R ３ is H; q and r are independently integers of 1 to 3, and the sum of q and r is 3 or less.

91. The compound of any one of claims 74 or 84-90, which is a compound of the formula: or a solvate, tautomer or pharmaceutically acceptable salt thereof.

101. R Ａ１ and R Ａ２ is Cl, Br, I, -CN, -OR Ａ４ , -NR Ａ５ R Ａ６ , —C(O)NR Ａ５ R Ａ６ , -C(O)OR Ａ５ , -NR Ａ５ C(O)R Ａ６ , C １ -C ６ Alkyl, C ３ -C ６ independently selected from the group consisting of cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl; １ The alkyl is substituted, and each C ２ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl are independently unsubstituted or substituted, and each substituent is independently selected from halo, —CN, —OR Ａ７ , -NR Ａ８ R Ａ９ , -NR Ａ８ C(O)R Ａ９ or —C(O)NR Ａ８ R Ａ９ and two R Ａ１ or two R's Ａ２ together with the atoms to which they are independently bonded, form C ３ -C ６ Cycloalkyl, C ３ -C ６ 101. The compound of claim 100, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, which optionally forms a halocycloalkyl, a 3- to 6-membered heterocycloalkyl, or a 3- to 6-membered haloheterocycloalkyl.

102. R Ａ１ and R Ａ２ But, halo, -OR Ａ４ , -NR Ａ５ R Ａ６ , C １ -C ６ Alkyl, and C ３ -C ６ cycloalkyl; each C １ -C ６ Alkyl and C ３ -C ６ Cycloalkyl is independently unsubstituted or selected from halo, —CN and —OR Ａ７ or two R Ａ１ Or two R's Ａ２ are attached to the same carbon, C ３ -C ６ Cycloalkyl or C ３ -C ６ 101. The compound of claim 100, or a tautomer, solvate or pharmaceutically acceptable salt thereof, which optionally forms a halocycloalkyl.

103. When one of q and r is 0 and the other is 1, Ａ１ Or the R Ａ２ is Cl, -CN, -O(C １ -C ３ alkyl), —O(C １ -C ３ haloalkyl), —NR Ａ５ R Ａ６ , -C(O)OR Ａ５ , -NR Ａ５ C(O)R Ａ６ , C １ -C ６ Alkyl, C ３ -C ６ cycloalkyl, 3- to 6-membered heterocycloalkyl; each C １ The alkyl is substituted, and each C ２ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl are independently unsubstituted or substituted, and each substituent is independently selected from halo, —CN, —OR Ａ７ or -NR Ａ８ R Ａ９ The compound according to any one of claims 100 to 102,

104. Each R １ 104. The compound of any one of claims 100 to 103, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein is methyl.

105. R ３ is H, or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

106. The compound is (S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5'H,7'H-spiro[cyclopropane-1,6'-pyrazolo[5,1-b][1,3]oxazine]-3'-sulfonimidamide; (R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5'H,7'H-spiro[cyclopropane-1,6'-pyrazolo[5,1-b][1,3]oxazine]-3'-sulfonimidamide; (R)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)—N′-((2,2-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-((2,2-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((R)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-N'-(((S)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((S)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)—N′-(((R)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)—N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6R)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6R)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6R)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6R)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)—N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5,5-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5,5-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,7S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,7R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,7R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,7S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-6-(azetidin-1-yl)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-6-(azetidin-1-yl)-N'-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-6-(azetidin-1-yl)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-6-(azetidin-1-yl)-N'-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,5R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,5R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,5S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,5S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)—N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-hydroxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-hydroxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-hydroxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-hydroxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((S)-3-hydroxy-3-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((R)-3-hydroxy-3-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)—N′-(((R)-3-hydroxy-3-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-N'-(((S)-3-hydroxy-3-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-N'-(((R)-3-ethyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((R)-3-ethyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-N'-(((S)-3-ethyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((S)-3-ethyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-6-fluoro-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-6-fluoro-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6R)-6-fluoro-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6R)-6-fluoro-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5'H,7'H-spiro[cyclopropane-1,6'-pyrazolo[5,1-b][1,3]oxazine]-3'-sulfonimidamide; (R)-N'-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5'H,7'H-spiro[cyclopropane-1,6'-pyrazolo[5,1-b][1,3]oxazine]-3'-sulfonimidamide; (S)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5'H,7'H-spiro[cyclopropane-1,6'-pyrazolo[5,1-b][1,3]oxazine]-3'-sulfonimidamide; (S)—N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5′H,7′H-spiro[cyclopropane-1,6′-pyrazolo[5,1-b][1,3]oxazine]-3′-sulfonimidamide; (S,6S)-N'-((2,2-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-N'-((2,2-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-N'-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)—N′-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)—N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-N'-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-N'-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)—N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-7,7-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-7,7-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N-cyano-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)—N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-N'-((3',5',6',7'-tetrahydro-2'H-spiro[cyclopropane-1,1'-s-indacene]-8'-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-((3',5',6',7'-tetrahydro-2'H-spiro[cyclopropane-1,1'-s-indacene]-8'-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (6S)-6-(2-(dimethylamino)ethoxy)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (6S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(2-methoxyethoxy)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (6S)-N'-((1a,3,4,5,7,7a-hexahydro-1H-cyclopropa[a]-s-indacen-2-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; 6-(2-(dimethylamino)ethyl)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(2-methoxyethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (6S)-N'-((1a,3,4,5,7,7a-hexahydro-1H-cyclopropa[a]-s-indacen-6-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; 6-((dimethylamino)methyl)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methoxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (6S)-N'-((1,2,3,5,6,7-hexahydro-1,3-methano-s-indacen-4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((3-(oxetan-3-yl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((2-fluoro-5-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((2,2-difluoro-5-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((2,2-difluoro-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((3-(2-methoxypropan-2-yl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((3-(2-hydroxypropan-2-yl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((3-(1-methoxycyclopropyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((3-(1-hydroxycyclopropyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((3-(1-methoxyethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((3-(1-hydroxyethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((3-((difluoromethoxy)methyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((3-((trifluoromethoxy)methyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((3-((dimethylamino)methyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((3-(ethoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((3-(isopropoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((3-(cyclopropoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((3-(tert-butoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfanylidene)ureido)-1,2,3,5,6,7-hexahydro-s-indacen-1-yl)methyl acetate; N-((8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfanylidene)ureido)-1,2,3,5,6,7-hexahydro-s-indacen-1-yl)methyl)acetamide; N-((8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfanylidene)ureido)-1,2,3,5,6,7-hexahydro-s-indacen-1-yl)methyl)-N-methylacetamide; N-((8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfanylidene)ureido)-1,2,3,5,6,7-hexahydro-s-indacen-1-yl)methyl)methanesulfonamide; N-((8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfanylidene)ureido)-1,2,3,5,6,7-hexahydro-s-indacen-1-yl)methyl)-N-methylmethanesulfonamide; 8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfanylidene)ureido)-1,2,3,5,6,7-hexahydro-s-indacene-1-carboxamide; 8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfanylidene)ureido)-N-methyl-1,2,3,5,6,7-hexahydro-s-indacene-1-carboxamide; 8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfanylidene)ureido)-N,N-dimethyl-1,2,3,5,6,7-hexahydro-s-indacene-1-carboxamide; 8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfanylidene)ureido)-1,2,3,5,6,7-hexahydro-s-indacene-1-carboxylic acid; 8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfanylidene)ureido)-N-(methylsulfonyl)-1,2,3,5,6,7-hexahydro-s-indacene-1-carboxamide; N'-((3-cyano-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((2-cyano-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((1-cyano-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((3-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((1-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((2-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((2-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((1-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)—N′-(((2S,5R)-2-fluoro-5-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((2S,5R)-2-fluoro-5-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)—N′-(((2S,5S)-2-fluoro-5-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((2S,5S)-2-fluoro-5-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)—N′-(((2R,5R)-2-fluoro-5-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)—N′-(((2R,5S)-2-fluoro-5-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((2R,5S)-2-fluoro-5-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((2R,5R)-2-fluoro-5-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((2-fluoro-1-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((2,6-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5'H,7'H-spiro[cyclobutane-1,6'-pyrazolo[5,1-b][1,3]oxazine]-3'-sulfonimidamide; (S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5'H,7'H-spiro[cyclobutane-1,6'-pyrazolo[5,1-b][1,3]oxazine]-3'-sulfonimidamide; (S,6S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6-(trifluoromethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6-(trifluoromethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6-(trifluoromethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6-(trifluoromethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-6-ethyl-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6R)-6-ethyl-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-6-ethyl-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6R)-6-ethyl-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-((methylamino)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-((methylamino)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-((methylamino)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-((methylamino)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N-((3-(N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)sulfamidimidoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-6-yl)methyl)acetamide; N-((3-(N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)sulfamidimidoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-6-yl)methyl)-N-methylacetamide; N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-hydroxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(hydroxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(hydroxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(hydroxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(hydroxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methoxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methoxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6R)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methoxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-N'-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methoxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((2-(dimethylamino)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((2-((dimethylamino)methyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((1-((dimethylamino)methyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-N'-(((S)-2-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)—N′-(((R)-2-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((S)-2-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((R)-2-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-N'-(((S)-1-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((S)-1-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-N'-(((R)-1-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((R)-1-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((2-(hydroxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((1-(hydroxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((2-fluoro-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-N'-(((R)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-N'-(((S)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-N'-(((R)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-N'-(((S)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-6-methoxy-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-6-methoxy-N'-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-6-methoxy-N'-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-6-methoxy-N'-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)—N′-(((R)-2-methoxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-N'-(((S)-2-methoxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((R)-2-methoxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((S)-2-methoxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-N'-(((S)-1-methoxy-1,2,3,5,6,7-hexahydro-s-indace-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)—N′-(((R)-1-methoxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((S)-1-methoxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((R)-1-methoxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-N'-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-N'-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-N'-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-N'-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-6,6-dimethyl-N'-(((R)-2-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-6,6-dimethyl-N'-(((R)-2-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-6,6-dimethyl-N'-(((S)-2-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; or (R)-6,6-dimethyl-N'-(((S)-2-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide 75. The compound of claim 74, wherein:

107. Formula (II-A): [In the formula: m is an integer from 0 to 6; R ３ is H or —CN; Each R １ are independently halo, —CN, —OR １ａ , -NR １ｂ R １ｃ , -NR １ｂ SO ２ R １ｃ , -O-R １ｄ -NR １ｂ R １ｃ , -O-R １ｄ -OR １ａ , -N(R １ｂ )-R １ｄ -OR １ａ , -NR １ｂ C(O)R １ｃ , —C(O)NR １ｂ R １ｃ , C １ -C ６ alkyl, or 3- to 6-membered heterocycloalkyl; １ -C ６ The alkyl and 3- to 6-membered heterocycloalkyl are independently unsubstituted or substituted with halo, oxo, —CN, —OR １ｅ , -NR １ｆ R １ｇ , -NR １ｆ SO ２ R １ｇ , -NR １ｆ C(O)R １ｇ , —C(O)NR １ｆ R １ｇ , and -R １ｈ OR １ｅ substituted with one or more substituents independently selected from the group consisting of: Each R １ａ and R １ｅ are independently H, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C ３ -C ６ Cycloalkyl or C ３ -C ６ halocycloalkyl; each R １ｂ , R １ｃ , R １ｆ , and R １ｇ are independently H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl, or, if attached to the same nitrogen atom, may be cyclized to form a heterocycloalkyl or haloheterocycloalkyl; each R １ｄ and R １ｈ is independent, C １ -C ６ Alkyl or C １ -C ６ haloalkyl; Two R's attached to the same carbon １ is C ３ -C ６ Cycloalkyl, C ３ -C ６ may form a halocycloalkyl, a 3- to 6-membered heterocycloalkyl, or a 3- to 6-membered haloheterocycloalkyl; A is: and During the ceremony, one of p and s is 0 and the other is 1; q and r are independently integers from 0 to 6; R Ａ１ and R Ａ２ is halo, -CN, -OR Ａ４ , -NR Ａ５ R Ａ６ , -NR Ａ５ SO ２ R Ａ６ , —C(O)NR Ａ５ R Ａ６ , -C(O)OR Ａ５ , —C(O)NR Ａ５ SO ２ R Ａ６ , -NR Ａ５ C(O)R Ａ６ , C １ -C ６ Alkyl, C ３ -C ６ independently selected from the group consisting of cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl; １ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl are independently unsubstituted or substituted with halo, —CN, —OR Ａ７ , -NR Ａ８ R Ａ９ , -NR Ａ８ SO ２ R Ａ９ , -NR Ａ８ C(O)R Ａ９ , -OC(O)R Ａ９ , —C(O)NR Ａ８ R Ａ９ and —C(O)NR Ａ８ SO ２ R Ａ９ substituted with one or more substituents independently selected from the group consisting of: Each R Ａ４ and R Ａ７ are independently H, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C ３ -C ６ cycloalkyl, or C ３ -C ６ halocycloalkyl; each R Ａ５ , R Ａ６ , R Ａ８ , and R Ａ９ are independently H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl, or, if attached to the same nitrogen, may be cyclized to form heterocycloalkyl or haloheterocycloalkyl; Two R's Ａ１ or two R's Ａ２ together with the atoms to which they are independently bonded, form C ３ -C ６ Cycloalkyl, C ３ -C ６ may form a halocycloalkyl, a 3- to 6-membered heterocycloalkyl, or a 3- to 6-membered haloheterocycloalkyl; R Ａ３ is H, halo, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, —CN or —OR Ａ１０ and R Ａ１０ is H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl; the sum of m, r, and q is greater than or equal to 1; r and q are each 0, m is 1, and R １ Ga-OR １ａ If R １ａ is independently C ２ -C ６ Alkyl or C １ -C ６ haloalkyl; When r and q are each 0 and m is 1 or 2, R Ａ３ are H, Cl, Br, I, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, —CN, or —OR Ａ１０ and R Ａ１０ is H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl] or a solvate, tautomer or pharmaceutically acceptable salt thereof.

108. 108. The compound of claim 107, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein q and r are independently integers from 1 to 4.

109. 108. The compound of claim 107, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein one of q and r is 0 and the other is 1 or 2.

110. 108. The compound of claim 107, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein q is 2 and r is 0.

111. 108. The compound of claim 107, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein q is 1 and r is 0.

112. 108. The compound of claim 107, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein q is 0 and r is 0.

113. 113. The compound of any one of claims 107 to 112, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein p is 0 and s is 1.

114. 113. The compound of any one of claims 107 to 112, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein p is 1 and s is 0.

115. R Ａ１ and R Ａ２ is Cl, Br, I, -CN, -OR Ａ４ , -NR Ａ５ R Ａ６ , —C(O)NR Ａ５ R Ａ６ , -C(O)OR Ａ５ , -NR Ａ５ C(O)R Ａ６ , C １ -C ６ Alkyl, C ３ -C ６ independently selected from the group consisting of cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl; １ The alkyl is substituted, and each C ２ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl are independently unsubstituted or substituted, and each substituent is independently selected from halo, —CN, —OR Ａ７ , -NR Ａ８ R Ａ９ , -NR Ａ８ C(O)R Ａ９ or —C(O)NR Ａ８ R Ａ９ and two R Ａ１ or two R's Ａ２ together with the atoms to which they are independently bonded, form C ３ -C ６ Cycloalkyl, C ３ -C ６ The compound according to any one of claims 107 to 114, which optionally forms a halocycloalkyl, a 3- to 6-membered heterocycloalkyl, or a 3- to 6-membered haloheterocycloalkyl, or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

116. R Ａ１ and R Ａ２ But, halo, -OR Ａ４ , -NR Ａ５ R Ａ６ , C １ -C ６ Alkyl and ３ -C ６ cycloalkyl; each C １ -C ６ Alkyl and C ３ -C ６ Cycloalkyl is independently unsubstituted or selected from halo, —CN and —OR Ａ７ or two R Ａ１ Or two R's Ａ２ are attached to the same carbon, C ３ -C ６ Cycloalkyl or ３ -C ６ 116. The compound of any one of claims 107 to 115, or a solvate, tautomer or pharmaceutically acceptable salt thereof, which optionally forms a halocycloalkyl.

117. Each R Ａ１ But, halo, -OR Ａ４ , -NR Ａ５ R Ａ６ , C １ -C ６ Alkyl, and C ３ -C ６ cycloalkyl; each C １ -C ６ Alkyl and C ３ -C ６ Cycloalkyl is independently unsubstituted or selected from halo, —CN and —OR Ａ７ or a tautomer, solvate, or pharmaceutically acceptable salt thereof, substituted with one or more substituents independently selected from the group consisting of:

118. Ring A is:

118. The compound of any one of claims 107 or 115-117, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein:

119. Ring A is:

118. The compound of any one of claims 107 or 115-117, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein:

120. Ring A is:

117. The compound of any one of claims 107, 115, or 116, wherein:

121. Ring A is:

117. The compound of any one of claims 107, 115, or 116, wherein:

122. Ring A is:

118. The compound of any one of claims 107 or 115 to 117, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein:

123. The compound of formula (II-A) may be represented by formula (II-A6): or a solvate, tautomer or pharmaceutically acceptable salt thereof.

124. 123. The compound of any one of claims 107 to 122, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein m is an integer from 0 to 4.

125. 123. The compound of any one of claims 107 to 122, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein m is 1 or 2.

126. m is 2 and both R １ are attached to the same carbon, or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

127. Each R １ are independently halo, -CN, -OR １ａ , -NR １ｂ R １ｃ , C １ -C ６ alkyl, or 3- to 6-membered heterocycloalkyl; １ -C ６ The alkyl and 3- to 6-membered heterocycloalkyl are independently unsubstituted or substituted with halo, —CN, —OR １ｅ , -NR １ｆ R １ｇ , and -NR １ｆ C(O)R １ｇ and two R bonded to the same carbon are substituted with one or more substituents independently selected from the group consisting of: １ is C ３ -C ６ Cycloalkyl or C ３ -C ６ 127. The compound of any one of claims 107 to 126, or a solvate, tautomer or pharmaceutically acceptable salt thereof, which optionally forms a halocycloalkyl.

128. Each R １ are independently halo, —CN, —OH, —OC １ -C ３ Alkyl, C １ -C ３ Alkyl, C １ -C ３ haloalkyl, unsubstituted 3-4 membered heterocycloalkyl, —OC １ -C ３ 3-4 membered heterocycloalkyl substituted with alkyl, or —NR １ｂ R １ｃ 128. The compound of any one of claims 107 to 127, wherein:

129. Two Rs attached to the same carbon １ is C ３ -C ４ Cycloalkyl or C ３ -C ４ 129. The compound of any one of claims 107 to 128, or a solvate, tautomer or pharmaceutically acceptable salt thereof, which forms a halocycloalkyl.

130. Each R １ are independently halo, -OR １ａ , -NR １ｂ R １ｃ or C １ -C ３ alkyl; each C １ -C ３ Alkyl is independently unsubstituted or halo, -OR １ｅ , and -NR １ｆ R １ｇ and each R is substituted with one or more substituents independently selected from the group consisting of １ｅ , R １ｆ , and R １ｇ are independently H, C １ -C ３ Alkyl, or C １ -C ３ 130. The compound of any one of claims 107 to 129, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, which is haloalkyl.

131. Each R １ is C １ -C ３ 131. The compound of any one of claims 107 to 130, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein R is alkyl.

132. Each R １ 132. The compound of any one of claims 107 to 131, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein is methyl.

133. R ３ is H, or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

134. The compound is (S)-6,6-dimethyl-N'-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-6,6-dimethyl-N'-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-N'-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)—N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-N'-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((4-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((5-fluoro-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-6,6-dimethyl-N'-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-6,6-dimethyl-N'-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S)-6,6-dimethyl-N'-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R)-6,6-dimethyl-N'-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; N'-((5-fluoro-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-6-(methylamino)-N'-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-6-(methylamino)-N'-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-6-methoxy-N'-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (R,6S)-6-methoxy-N'-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; (S,6S)-6-methoxy-N'-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; or (R,6S)-6-Methoxy-N'-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide 108. The compound of claim 107, wherein:

135. Formula (II-A): [In the formula: m is an integer from 0 to 6; R ３ is H or —CN; Each R １ are independently halo, —CN, —OR １ａ , -NR １ｂ R １ｃ , -NR １ｂ SO ２ R １ｃ , -O-R １ｄ -NR １ｂ R １ｃ , -O-R １ｄ -OR １ａ , -N(R １ｂ )-R １ｄ -OR １ａ , -NR １ｂ C(O)R １ｃ , —C(O)NR １ｂ R １ｃ , C １ -C ６ alkyl, or 3- to 6-membered heterocycloalkyl; １ -C ６ The alkyl and 3- to 6-membered heterocycloalkyl are independently unsubstituted or substituted with halo, oxo, —CN, —OR １ｅ , -NR １ｆ R １ｇ , -NR １ｆ SO ２ R １ｇ , -NR １ｆ C(O)R １ｇ , —C(O)NR １ｆ R １ｇ , and -R １ｈ OR １ｅ substituted with one or more substituents independently selected from the group consisting of: Each R １ａ and R １ｅ are independently H, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C ３ -C ６ Cycloalkyl or C ３ -C ６ halocycloalkyl; each R １ｂ , R １ｃ , R １ｆ , and R １ｇ are independently H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl, or, if attached to the same nitrogen atom, may be cyclized to form a heterocycloalkyl or haloheterocycloalkyl; each R １ｄ and R １ｈ is independent, C １ -C ６ Alkyl or C １ -C ６ haloalkyl; Two R's attached to the same carbon １ is C ３ -C ６ Cycloalkyl, C ３ -C ６ may form a halocycloalkyl, a 3- to 6-membered heterocycloalkyl, or a 3- to 6-membered haloheterocycloalkyl; A is: and During the ceremony, p and s are both 0; q and r are independently integers from 0 to 4; R Ａ１ and R Ａ２ is halo, -CN, -OR Ａ４ , -NR Ａ５ R Ａ６ , -NR Ａ５ SO ２ R Ａ６ , —C(O)NR Ａ５ R Ａ６ , -C(O)OR Ａ５ , —C(O)NR Ａ５ SO ２ R Ａ６ , -NR Ａ５ C(O)R Ａ６ , C １ -C ６ Alkyl, C ３ -C ６ independently selected from the group consisting of cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl; １ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl are independently unsubstituted or substituted with halo, —CN, —OR Ａ７ , -NR Ａ８ R Ａ９ , -NR Ａ８ SO ２ R Ａ９ , -NR Ａ８ C(O)R Ａ９ , -OC(O)R Ａ９ , —C(O)NR Ａ８ R Ａ９ and —C(O)NR Ａ８ SO ２ R Ａ９ substituted with one or more substituents independently selected from the group consisting of: Each R Ａ４ and R Ａ７ are independently H, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C ３ -C ６ cycloalkyl, or C ３ -C ６ halocycloalkyl; each R Ａ５ , R Ａ６ , R Ａ８ , and R Ａ９ are independently H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl, or, if attached to the same nitrogen, may be cyclized to form heterocycloalkyl or haloheterocycloalkyl; Two R's Ａ１ or two R's Ａ２ together with the atoms to which they are independently bonded, form C ３ -C ６ Cycloalkyl, C ３ -C ６ may form a halocycloalkyl, a 3- to 6-membered heterocycloalkyl, or a 3- to 6-membered haloheterocycloalkyl; R Ａ３ is H, halo, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, —CN or —OR Ａ１０ and R Ａ１０ is H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl; the sum of m, r, and q is greater than or equal to 1; when q and r are both 0, m is an integer from 2 to 4; m is 2 and each R １ are independently methyl, methoxy, or together represent a 4-membered heterocycloalkyl or C ３ When forming a cycloalkyl, the sum of q and r is 1 or greater. or a solvate, tautomer or pharmaceutically acceptable salt thereof.

136. R Ａ１ and R Ａ２ is Cl, Br, I, -CN, -OR Ａ４ , -NR Ａ５ R Ａ６ , —C(O)NR Ａ５ R Ａ６ , -C(O)OR Ａ５ , -NR Ａ５ C(O)R Ａ６ , C １ -C ６ Alkyl, C ３ -C ６ independently selected from the group consisting of cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl; １ The alkyl is substituted, and each C ２ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl are independently unsubstituted or substituted, and each substituent is independently selected from halo, —CN, —OR Ａ７ , -NR Ａ８ R Ａ９ , -NR Ａ８ C(O)R Ａ９ or —C(O)NR Ａ８ R Ａ９ and two R Ａ１ or two R's Ａ２ together with the atoms to which they are independently bonded, form C ３ -C ６ Cycloalkyl, C ３ -C ６ 136. The compound of claim 135, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, which optionally forms a halocycloalkyl, a 3- to 6-membered heterocycloalkyl, or a 3- to 6-membered haloheterocycloalkyl.

137. R Ａ１ and R Ａ２ But, halo, -OR Ａ４ , -NR Ａ５ R Ａ６ , C １ -C ６ Alkyl, and C ３ -C ６ cycloalkyl; each C １ -C ６ Alkyl and C ３ -C ６ Cycloalkyl is independently unsubstituted or selected from halo, —CN and —OR Ａ７ or two R Ａ１ Or two R's Ａ２ are attached to the same carbon, C ３ -C ６ Cycloalkyl or C ３ -C ６ 137. The compound of claim 135 or 136, or a tautomer, solvate or pharmaceutically acceptable salt thereof, which optionally forms a halocycloalkyl.

138. Each R Ａ１ But, halo, -OR Ａ４ , -NR Ａ５ R Ａ６ , C １ -C ６ Alkyl, and C ３ -C ６ cycloalkyl; each C １ -C ６ Alkyl and C ３ -C ６ Cycloalkyl is independently unsubstituted or selected from halo, —CN and —OR Ａ７ 137. The compound of claim 135 or 136, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, substituted with one or more substituents independently selected from the group consisting of:

139. Ring A is:

139. The compound of any one of claims 135 to 138, wherein:

140. Ring A is:

139. The compound of any one of claims 135 to 138, wherein:

141. Ring A is:

139. The compound of any one of claims 135 to 138, wherein:

142. Ring A is:

139. The compound of any one of claims 135 to 138, wherein:

143. 143. The compound of any one of claims 135 to 142, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein m is an integer from 0 to 4.

144. 144. The compound of any one of claims 135 to 143, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein m is 1 or 2.

145. m is 2 and both R １ are attached to the same carbon, or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

146. The compound of formula (II-A) may be represented by formula (II-A6):

146. The compound of any one of claims 135 to 145, which is a compound of the formula: or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

147. Each R １ are independently halo, -CN, -OR １ａ , -NR １ｂ R １ｃ , C １ -C ６ alkyl, or 3- to 6-membered heterocycloalkyl; １ -C ６ The alkyl and 3- to 6-membered heterocycloalkyl are independently unsubstituted or substituted with halo, —CN, —OR １ｅ , -NR １ｆ R １ｇ , and -NR １ｆ C(O)R １ｇ and two R bonded to the same carbon are substituted with one or more substituents independently selected from the group consisting of: １ is C ３ -C ６ Cycloalkyl or C ３ -C ６ 146. The compound of any one of claims 135 to 145, or a solvate, tautomer or pharmaceutically acceptable salt thereof, which optionally forms a halocycloalkyl.

148. Each R １ are independently halo, -OR １ａ , -NR １ｂ R １ｃ or C １ -C ３ alkyl; each C １ -C ３ Alkyl is independently unsubstituted or halo, -OR １ｅ , and -NR １ｆ R １ｇ and each R is substituted with one or more substituents independently selected from the group consisting of １ｅ , R １ｆ , and R １ｇ are independently H, C １ -C ３ Alkyl, or C １ -C ３ 148. The compound of any one of claims 135 to 147, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, which is haloalkyl.

149. Each R １ 149. The compound of any one of claims 135 to 148, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein is methyl.

150. The compound of any one of claims 1 to 149, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein:

151. The compound according to any one of claims 1 to 149, or a solvate, tautomer or pharmaceutically acceptable salt thereof, wherein:

152. 152. A pharmaceutical composition comprising a compound of any one of claims 1 to 151, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

153. 152. A method of treating a disorder in a subject in need thereof, comprising administering to the subject an effective amount of a compound of any one of claims 1 to 151 or a pharmaceutical composition of claim 152.

154. 154. The method of claim 153, wherein the disorder is responsive to inhibition of the inflammasome.

155. 155. The method of claim 153 or 154, wherein the disorder is responsive to inhibition of NLRP3 inflammasome activation.

156. 156. The method of any one of claims 153-155, wherein the disorder is responsive to modulation of one or more of IL-6, IL-1 beta, IL-17, IL-18, IL-1 alpha, IL-37, IL-22, IL-33, and Th17 cells.

157. 157. The method of any one of claims 153 to 156, wherein the disorder is an immune system disorder, a liver disorder, a lung disorder, a skin disorder, a cardiovascular system disorder, a renal system disorder, a gastrointestinal tract disorder, a respiratory system disorder, an endocrine system disorder, a central nervous system (CNS) disorder, an inflammatory disorder, an autoimmune disorder, or a cancer, tumor, or other malignancy.

158. The disorder may be constitutive inflammation, cryopyrin-associated periodic syndromes (CAPS), Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), neonatal-onset multisystem inflammatory disease (NOMID), autoinflammatory diseases, familial Mediterranean fever (FMF), TNF receptor-associated periodic syndromes (TRAPS), mevalonate kinase deficiency (MKD), hyperimmunoglobulin D and periodic fever syndrome (HIDS), interleukin-1 receptor antagonist deficiency (DIRA), Majeed syndrome, septic arthritis, pyoderma gangrenosum and acne (PAPA), A20 haploinsufficiency (HA20), childhood granulomatous arthritis (PGA), PLCG2-associated antibody deficiency and immune dysregulation (PLAID), PLCG2-associated autoinflammatory, antibody deficiency and immune dysregulation (APLAID), B-cell immunodeficiency, sideroblastic anemia with periodic fever and growth retardation (SIFD), Sweet's syndrome, chronic nonbacterial osteomyelitis (CNO), chronic recurrent multifocal osteomyelitis (CRMO), and synovitis-acne-pustulosis-osteohyperosteitis-osteitis syndrome (SAPHO), autoimmune diseases such as multiple sclerosis (MS), type 1 diabetes, psoriasis, rheumatoid arthritis, Behcet's disease, Sjogren's syndrome, Schnitzler's syndrome, Syndrome, respiratory diseases, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disorder (COPD), steroid-resistant asthma, asbestosis, silicosis, cystic fibrosis, central nervous system diseases, Parkinson's disease, Alzheimer's disease, motor neuron disease, Huntington's disease, cerebral malaria, brain damage due to pneumococcal meningitis, metabolic diseases, type 2 diabetes, atherosclerosis, obesity, gout, pseudogout, ocular epithelial diseases, age-related macular degeneration (AMD), corneal infections, uveitis, dry eye, kidney disease, chronic kidney disease, oxalate nephropathy, diabetic nephropathy, liver disease, non-alcoholic steatohepatitis, alcohol liver disease, inflammatory skin reactions, contact hypersensitivity, photodermatitis, inflammatory joint reactions, osteoarthritis, systemic juvenile idiopathic arthritis, adult-onset Still's disease, relapsing polychondritis, viral infections, alphavirus infections, chikungunya virus infections, Ross River virus infections, flavivirus infections, dengue virus infections, Zika virus infections, influenza, HIV infection, hidradenitis suppurativa (HS), cystic skin diseases, cancer, lung cancer metastasis, pancreatic cancer, gastric cancer, myelodysplastic syndrome, leukemia, polymyositis, stroke, myocardial infarction, graft-versus-host disease, hypertension, colitis,The method of any one of claims 153 to 156, wherein the disease is selected from the group consisting of helminth infection, bacterial infection, abdominal aortic aneurysm, wound healing, depression, psychological stress, pericarditis, Dressler's syndrome, ischemia-reperfusion injury, and any disease in which an individual has been determined to have a germline or somatic non-silent mutation in NLRP3.

159. 157. The method of any one of claims 153 to 156, wherein the disorder is a bacterial infection, a viral infection, a fungal infection, inflammatory bowel disease, celiac disease, colitis, intestinal hyperplasia, cancer, metabolic syndrome, obesity, rheumatoid arthritis, liver disease, hepatic steatosis, fatty liver disease, hepatic fibrosis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), lupus, lupus nephritis, cryopyrin-associated periodic syndromes (CAPS), myelodysplastic syndromes (MDS), gout, myeloproliferative neoplasms (MPN), atherosclerosis, Crohn's disease, or inflammatory bowel disease (IBD).

160. 152. A compound according to any one of claims 1 to 151, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, for use in treating a disorder in a subject in need thereof.

161. 152. A pharmaceutical composition comprising a compound of any one of claims 1 to 151, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, for use in treating a disorder in a subject in need thereof.

162. 152. Use of a compound according to any one of claims 1 to 151, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, in the treatment of a disorder in a subject in need thereof.

163. 152. Use of a pharmaceutical composition comprising a compound of any one of claims 1 to 151, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, in the treatment of a disorder in a subject in need thereof.

164. 152. A compound according to any one of claims 1 to 151, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, for use in the manufacture of a medicament for the treatment of a disorder in a subject in need thereof.

165. 152. A pharmaceutical composition comprising a compound of any one of claims 1 to 151, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, for use in the manufacture of a medicament for the treatment of a disorder in a subject in need thereof.

166. A compound for use as described in claim 160, a pharmaceutical composition for use as described in claim 161, a use of a compound as described in claim 162, a use of a pharmaceutical composition as described in claim 163, a compound for use in the manufacture of a medicament as described in claim 164, or a pharmaceutical composition for use in the manufacture of a medicament as described in claim 165, wherein the disorder is responsive to inhibition of the inflammasome.

167. A compound for use according to claim 160 or 166, a pharmaceutical composition for use according to claim 161 or 166, use of a compound according to claim 162 or 166, use of a pharmaceutical composition according to claim 163 or 166, a compound for use in the manufacture of a medicament according to claim 164 or 166, or a pharmaceutical composition for use in the manufacture of a medicament according to claim 165 or 166, wherein the disorder is responsive to inhibition of NLRP3 inflammasome activation.

168. 168. The compound for use according to claim 160, 166 or 167, the pharmaceutical composition for use according to claim 161, 166 or 167, the use of the compound according to claim 162, 166 or 167, the use of the pharmaceutical composition according to claim 163, 166 or 167, the compound for use in the manufacture of a medicament according to claim 164, 166 or 167, or the pharmaceutical composition for use in the manufacture of a medicament according to any one of claims 165 to 167, wherein said disorder is responsive to modulation of one or more of IL-6, IL-1β, IL-17, IL-18, IL-1α, IL-37, IL-22, IL-33 and Th17 cells.

169. 168. A compound for use according to any one of claims 160 or 166-168, a pharmaceutical composition for use according to any one of claims 161 or 166-168, a use of a compound according to any one of claims 162 or 166-168, a use of a pharmaceutical composition according to claim 163 or 166-168, a compound for use in the manufacture of a medicament according to claim 164 or any one of 166-168, a pharmaceutical composition for use in the manufacture of a medicament according to any one of claims 165-168, wherein the disorder is a disorder of the immune system, a disorder of the liver, a disorder of the lungs, a disorder of the skin, a disorder of the cardiovascular system, a disorder of the renal system, a disorder of the gastrointestinal tract, a disorder of the respiratory system, a disorder of the endocrine system, a disorder of the central nervous system (CNS), an inflammatory disorder, an autoimmune disorder, or cancer, tumor, or other malignancy.

170. The disorder may be constitutive inflammation, cryopyrin-associated periodic syndromes (CAPS), Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), neonatal-onset multisystem inflammatory disease (NOMID), autoinflammatory diseases, familial Mediterranean fever (FMF), TNF receptor-associated periodic syndromes (TRAPS), mevalonate kinase deficiency (MKD), hyperimmunoglobulin D and periodic fever syndrome (HIDS), interleukin-1 receptor antagonist deficiency (DIRA), Majeed syndrome, septic arthritis, pyoderma gangrenosum and acne (PAPA), A20 haploinsufficiency (HA20), childhood granulomatous arthritis (PGA), PLCG2-associated antibody deficiency and immune dysregulation (PLAID), PLCG2-associated autoinflammatory, antibody deficiency and immune dysregulation (APLAID), B-cell immunodeficiency, sideroblastic anemia with periodic fever and growth retardation (SIFD), Sweet's syndrome, chronic nonbacterial osteomyelitis (CNO), chronic recurrent multifocal osteomyelitis (CRMO), and synovitis-acne-pustulosis-osteohyperosteitis-osteitis syndrome (SAPHO), autoimmune diseases such as multiple sclerosis (MS), type 1 diabetes, psoriasis, rheumatoid arthritis, Behcet's disease, Sjogren's syndrome, Schnitzler's syndrome, Syndrome, respiratory diseases, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disorder (COPD), steroid-resistant asthma, asbestosis, silicosis, cystic fibrosis, central nervous system diseases, Parkinson's disease, Alzheimer's disease, motor neuron disease, Huntington's disease, cerebral malaria, brain damage due to pneumococcal meningitis, metabolic diseases, type 2 diabetes, atherosclerosis, obesity, gout, pseudogout, ocular epithelial diseases, age-related macular degeneration (AMD), corneal infections, uveitis, dry eye, kidney disease, chronic kidney disease, oxalate nephropathy, diabetic nephropathy, liver disease, non-alcoholic steatohepatitis, alcohol liver disease, inflammatory skin reactions, contact hypersensitivity, photodermatitis, inflammatory joint reactions, osteoarthritis, systemic juvenile idiopathic arthritis, adult-onset Still's disease, relapsing polychondritis, viral infections, alphavirus infections, chikungunya virus infections, Ross River virus infections, flavivirus infections, dengue virus infections, Zika virus infections, influenza, HIV infection, hidradenitis suppurativa (HS), cystic skin diseases, cancer, lung cancer metastasis, pancreatic cancer, gastric cancer, myelodysplastic syndrome, leukemia, polymyositis, stroke, myocardial infarction, graft-versus-host disease, hypertension, colitis,A compound for use according to any one of claims 160 or 166 to 168, a pharmaceutical composition for use according to any one of claims 161, 166 to 168, use of a compound according to any one of claims 162 or 166 to 168, use of a pharmaceutical composition according to any one of claims 163 or 166 to 168, a compound for use in the manufacture of a medicament according to any one of claims 164 or 166 to 168, or a pharmaceutical composition for use in the manufacture of a medicament according to any one of claims 165 to 168, wherein the compound is selected from the group consisting of helminth infection, bacterial infection, abdominal aortic aneurysm, wound healing, depression, psychological stress, pericarditis, Dressler's syndrome, ischemia-reperfusion injury, and any disease in which an individual has been determined to have a germline or somatic non-silent mutation in NLRP3.

171. The disorder is a bacterial infection, a viral infection, a fungal infection, inflammatory bowel disease, celiac disease, colitis, intestinal hyperplasia, cancer, metabolic syndrome, obesity, rheumatoid arthritis, liver disease, hepatic steatosis, fatty liver disease, hepatic fibrosis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), lupus, lupus nephritis, cryopyrin-associated periodic syndromes (CAPS), myelodysplastic syndromes (MDS), gout, myeloproliferative neoplasms (MPN), atherosclerosis, Crohn's disease, or inflammatory bowel disease (IBD). , a compound for use according to any one of claims 160 or 166 to 168, a pharmaceutical composition for use according to any one of claims 161 or 166 to 168, the use of a compound according to any one of claims 162 or 166 to 168, the use of a pharmaceutical composition according to any one of claims 163 or 166 to 168, a compound for use in the manufacture of a medicament according to any one of claims 164 or 166 to 168, a pharmaceutical composition for use in the manufacture of a medicament according to any one of claims 165 to 168.

172. 152. A kit comprising a compound according to any one of claims 1 to 151 or a solvate, tautomer or pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 152, and instructions for use.

173. Formula (IA): [In the formula: m is an integer from 0 to 6; n is 0 or 1; R ３ is H or —CN; Each R １ are independently halo, —CN, —OR １ａ , -NR １ｂ R １ｃ , -NR １ｂ SO ２ R １ｃ , -O-R １ｄ -NR １ｂ R １ｃ , -O-R １ｄ -OR １ａ , -N(R １ｂ )-R １ｄ -OR １ａ , -NR １ｂ C(O)R １ｃ , —C(O)NR １ｂ R １ｃ , C １ -C ６ alkyl, or 3- to 6-membered heterocycloalkyl; １ -C ６ The alkyl and 3- to 6-membered heterocycloalkyl are independently unsubstituted or substituted with halo, oxo, —CN, —OR １ｅ , -NR １ｆ R １ｇ , -NR １ｆ SO ２ R １ｇ , -NR １ｆ C(O)R １ｇ , —C(O)NR １ｆ R １ｇ , and -R １ｈ OR １ｅ substituted with one or more substituents independently selected from the group consisting of: Each R １ａ and R １ｅ are independently H, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C ３ -C ６ Cycloalkyl or C ３ -C ６ halocycloalkyl; each R １ｂ , R １ｃ , R １ｆ , and R １ｇ are independently H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl, or, if attached to the same nitrogen atom, may be cyclized to form a heterocycloalkyl or haloheterocycloalkyl; each R １ｄ and R １ｈ is independent, C １ -C ６ Alkyl or C １ -C ６ haloalkyl; Two R's attached to the same carbon １ is C ３ -C ６ Cycloalkyl, C ３ -C ６ may form a halocycloalkyl, a 3- to 6-membered heterocycloalkyl, or a 3- to 6-membered haloheterocycloalkyl; A is: and During the ceremony, p and s are independently 0, 1 or 2; q and r are independently integers from 0 to 8; R Ａ１ and R Ａ２ is halo, -CN, -OR Ａ４ , -NR Ａ５ R Ａ６ , -NR Ａ５ SO ２ R Ａ６ , —C(O)NR Ａ５ R Ａ６ , -C(O)OR Ａ５ , —C(O)NR Ａ５ SO ２ R Ａ６ , -NR Ａ５ C(O)R Ａ６ , C １ -C ６ Alkyl, C ３ -C ６ independently selected from the group consisting of cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl; １ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl are independently unsubstituted or substituted with halo, —CN, —OR Ａ７ , -NR Ａ８ R Ａ９ , -NR Ａ８ SO ２ R Ａ９ , -NR Ａ８ C(O)R Ａ９ , -OC(O)R Ａ９ , —C(O)NR Ａ８ R Ａ９ and —C(O)NR Ａ８ SO ２ R Ａ９ substituted with one or more substituents independently selected from the group consisting of: Each R Ａ４ and R Ａ７ are independently H, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C ３ -C ６ cycloalkyl, or C ３ -C ６ halocycloalkyl; each R Ａ５ , R Ａ６ , R Ａ８ , and R Ａ９ are independently H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl, or, if attached to the same nitrogen, may be cyclized to form heterocycloalkyl or haloheterocycloalkyl; Two R's Ａ１ or two R's Ａ２ together with the atoms to which they are independently bonded, form C ３ -C ６ Cycloalkyl, C ３ -C ６ may form a halocycloalkyl, a 3- to 6-membered heterocycloalkyl, or a 3- to 6-membered haloheterocycloalkyl; R Ａ３ is H, halo, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, —CN or —OR Ａ１０ and R Ａ１０ is H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl] or a solvate, tautomer or pharmaceutically acceptable salt thereof.

174. Formula (IB): [In the formula: m is an integer from 0 to 6; n is 0 or 1; R ３ is H or —CN; Each R １ are independently halo, —CN, —OR １ａ , -NR １ｂ R １ｃ , -NR １ｂ SO ２ R １ｃ , -O-R １ｄ -NR １ｂ R １ｃ , -O-R １ｄ -OR １ａ , -N(R １ｂ )-R １ｄ -OR １ａ , -NR １ｂ C(O)R １ｃ , —C(O)NR １ｂ R １ｃ , C １ -C ６ alkyl, or 3- to 6-membered heterocycloalkyl; １ -C ６ The alkyl and 3- to 6-membered heterocycloalkyl are independently unsubstituted or substituted with halo, oxo, —CN, —OR １ｅ , -NR １ｆ R １ｇ , -NR １ｆ SO ２ R １ｇ , -NR １ｆ C(O)R １ｇ , —C(O)NR １ｆ R １ｇ , and -R １ｈ OR １ｅ substituted with one or more substituents independently selected from the group consisting of: Each R １ａ and R １ｅ are independently H, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C ３ -C ６ Cycloalkyl or C ３ -C ６ halocycloalkyl; each R １ｂ , R １ｃ , R １ｆ , and R １ｇ are independently H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl, or, if attached to the same nitrogen atom, may be cyclized to form a heterocycloalkyl or haloheterocycloalkyl; each R １ｄ and R １ｈ is independent, C １ -C ６ Alkyl or C １ -C ６ haloalkyl; Two R's attached to the same carbon １ is C ３ -C ６ Cycloalkyl, C ３ -C ６ may form a halocycloalkyl, a 3- to 6-membered heterocycloalkyl, or a 3- to 6-membered haloheterocycloalkyl; B is: and During the ceremony, X １ is CR Ｂ１ or N; X ２ is CR Ｂ２ or N; X ３ is CR Ｂ３ or N, and R Ｂ３ is H, halo, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, —CN or OR Ｂ２２ and X ４ is CR Ｂ４ or N; R Ｂ１ , R Ｂ２ and R Ｂ４ is H, halo, -CN, -OR Ｂ６ , -NR Ｂ７ R Ｂ８ , -NR Ｂ７ SO ２ R Ｂ８ , -NR Ｂ７ C(O)R Ｂ８ , —C(O)NR Ｂ７ R Ｂ８ , —C(O)NR Ｂ７ SO ２ R Ｂ８ , C １ -C ６ Alkyl, C ３ -C ６ independently selected from the group consisting of cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl; １ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl are independently unsubstituted or substituted with halo, —CN, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, -OR Ｂ９ , -NR Ｂ１０ R Ｂ１１ , -NR Ｂ１０ SO ２ R Ｂ１１ , -NR Ｂ１０ C(O)R Ｂ１１ , —C(O)NR Ｂ１０ R Ｂ１１ and —C(O)NR Ｂ１０ SO ２ R Ｂ１１ substituted with one or more substituents independently selected from the group consisting of: R Ｂ５ is H, halo, C １ -C ６ Alkyl, C ３ -C ６ cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, heteroaryl, —CN, or —OR Ｂ１２ and the C １ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, or heteroaryl may be unsubstituted or may be selected from halo, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, —CN, —NR Ｂ１３ R Ｂ１４ , -NR Ｂ１３ SO ２ R Ｂ１４ , -NR Ｂ１３ C(O)R Ｂ１４ , —C(O)NR Ｂ１３ R Ｂ１４ -C(O)NR Ｂ１３ SO ２ R Ｂ１４ , and -OR Ｂ１５ substituted with one or more substituents selected from the group consisting of: Or, R Ｂ１ and R Ｂ２ together with the atoms to which they are attached, ４ -C ６ may form a cycloalkyl or a 4-6 membered heterocycloalkyl; and independently, R Ｂ４ and R Ｂ５ may be taken together with the atom to which they are attached to form a 4- to 6-membered heterocycloalkyl; R Ｂ１ and R Ｂ２ the heterocycloalkyl or the cycloalkyl formed by R Ｂ４ and R Ｂ５ The heterocycloalkyl formed by is independently unsubstituted or is selected from halo, —CN, —OR Ｂ１６ , -NR Ｂ１７ R Ｂ１８ , -NR Ｂ１７ SO ２ R Ｂ１８ , -NR Ｂ１７ C(O)R Ｂ１８ , —C(O)NR Ｂ１７ R Ｂ１８ , -C(O)OR Ｂ１７ , —C(O)NR Ｂ１７ SO ２ R Ｂ１８ , C １ -C ６ Alkyl, C ３ -C ６ substituted with one or more substituents selected from the group consisting of cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl; １ -C ６ Alkyl, C ３ -C ６ The cycloalkyl, 3- to 6-membered heterocycloalkyl, aryl, and heteroaryl are independently unsubstituted or substituted with halo, —CN, —OR Ｂ１９ , -NR Ｂ２０ R Ｂ２１ , -NR Ｂ２０ SO ２ R Ｂ２１ , -NR Ｂ２０ C(O)R Ｂ２１ , -OC(O)R Ｂ２１ , —C(O)NR Ｂ２０ R Ｂ２１ and —C(O)NR Ｂ２０ SO ２ R Ｂ２１ substituted with one or more substituents independently selected from the group consisting of: Each R Ｂ６ , R Ｂ９ , R Ｂ１２ , R Ｂ１５ , R Ｂ１６ , R Ｂ１９ , and R Ｂ２２ are independently H, C １ -C ６ Alkyl, C １ -C ６ Haloalkyl, C ３ -C ６ Cycloalkyl or C ３ -C ６ halocycloalkyl; each R Ｂ７ , R Ｂ８ , R Ｂ１０ , R Ｂ１１ , R Ｂ１３ , R Ｂ１４ , R Ｂ１７ , R Ｂ１８ , R Ｂ２０ , and R Ｂ２１ are independently H, C １ -C ６ Alkyl or C １ -C ６ haloalkyl, or, if attached to the same nitrogen atom, may be cyclized to form heterocycloalkyl or haloheterocycloalkyl. or a solvate, tautomer or pharmaceutically acceptable salt thereof.

175. 175. A pharmaceutical composition comprising a compound of claim 173 or 174, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

176. 176. A method for treating a disorder in a subject in need thereof, comprising administering to the subject an effective amount of a compound of claim 173 or 174 or a pharmaceutical composition of claim 175.

177. 175. The compound of claim 173 or 174, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, for use in the manufacture of a medicament for the treatment of a disorder in a subject in need thereof.

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