Il-17a inhibitors

Abstract

This invention provides certain imidazotriazine compounds of Formula I as IL-17A inhibitors, pharmaceutical compositions thereof, and methods of using compounds of Formula I or II to treat psoriasis, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, psoriatic arthritis, axial spondylitis, adhesive spondylitis, hidradenitis suppurativa, systemic lupus erythematosus, palmoplantar pustulosis (PPP), atopic dermatitis, asthma, non-infectious uveitis, or COPD.

Claims

1. A compound of the following formula or a pharmaceutically acceptable salt, stereoisomer, or hydrate thereof, wherein: R1 series; R2 series or; R3 series or; and R4 series or.

2. The compound of claim 1 or a pharmaceutically acceptable salt, stereoisomer or hydrate thereof, wherein R2 is a compound.

3. The compound of claim 1 or a pharmaceutically acceptable salt, stereoisomer or hydrate thereof, wherein R2 is a derivative.

4. The compound of claim 1 or a pharmaceutically acceptable salt, stereoisomer or hydrate thereof, wherein R2 is a derivative.

5. The compound of claim 1 or a pharmaceutically acceptable salt, stereoisomer or hydrate thereof, wherein R2 is a derivative.

6. The compound of claim 1 or a pharmaceutically acceptable salt, stereoisomer or hydrate thereof, wherein R2 is a derivative.

7. The compound of claim 1 or a pharmaceutically acceptable salt, stereoisomer or hydrate thereof, wherein R2 is a derivative.

8. The compound of claim 1 or a pharmaceutically acceptable salt, stereoisomer or hydrate thereof, wherein R2 is a derivative.

9. The compound of claim 1 or a pharmaceutically acceptable salt, stereoisomer or hydrate thereof, wherein R2 is a derivative.

10. The compound of any one of claims 2 to 9, or a pharmaceutically acceptable salt, stereoisomer or hydrate thereof, wherein the R3 group is present.

11. The compound of any one of claims 2 to 9, or a pharmaceutically acceptable salt, stereoisomer or hydrate thereof, wherein the R3 group is present.

12. The compound of any one of claims 2 to 9, or a pharmaceutically acceptable salt, stereoisomer or hydrate thereof, wherein the R3 group is present.

13. The compound of any one of claims 2 to 9, or a pharmaceutically acceptable salt, stereoisomer or hydrate thereof, wherein the R3 group is present.

14. The compound of any one of claims 2 to 9, or a pharmaceutically acceptable salt, stereoisomer or hydrate thereof, wherein the R3 group is present.

15. A compound of any one of claims 2 to 9, or a pharmaceutically acceptable salt, stereoisomer, or hydrate thereof, wherein the R3 group is present.

16. The compound of any one of claims 2 to 9, or a pharmaceutically acceptable salt, stereoisomer or hydrate thereof, wherein the R3 group is present.

17. A compound of any one of claims 2 to 9, or a pharmaceutically acceptable salt, stereoisomer or hydrate thereof, wherein the R3 group is present.

18. The compound of claim 1 or a pharmaceutically acceptable salt, stereoisomer, or hydrate thereof, selected from the group consisting of: N-((S)-(3-(1-(2-amino-2-sideoxyethyl)hexahydropyridin-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-methyl-1H-pyrazol-5-methamide; N-((S)-(3-((R)-4,4-difluoro-1-methylhexahydropyridin-3-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-methyl-1H-pyrazol-5-methamide (isomer 1); N-((S)-(3-((R)-4,4-difluoro-1-methylhexahydropyridin-3-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-methyl-1H-pyrazol-5-methamide (isomer 2); N-((S)-(3-((R)-4,4-difluoro-1-methylhexahydropyridin-3-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-1,4-dihydroimidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-(2-fluoroethyl)-1H-pyrazole-5-methamide (isomer 1); N-((S)-(3-((R)-4,4-difluoro-1-methylhexahydropyridin-3-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-1,4-dihydroimidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-(2-fluoroethyl)-1H-pyrazole-5-methoxyamine (isomer 2); 1-Methyl-N-((S)-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((S)-tetrahydrofuran-3-yl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1H-pyrazole-5-methamide (isomer 1);1-Methyl-N-((S)-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((R)-tetrahydrofuran-3-yl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1H-pyrazol-5-methylamine (isomer 2); 1-Methyl-N-((S)-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((3-methyloxetane-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1H-pyrazol-5-methylamine; 1-Methyl-N-((S)-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((R)-tetrahydro-2H-pyran-3-yl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1H-pyrazol-5-methamide (isomer 1); 1-Methyl-N-((S)-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((R)-tetrahydro-2H-pyran-3-yl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1H-pyrazol-5-methamide (isomer 2); 2-Ethyl-N-((S)-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((R)-tetrahydro-2H-pyran-3-yl)-1,4-dihydroimidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-4,5-dihydro-1l2,2l4-pyrazol-3-methamide (isomer 1); 2-Ethyl-N-((S)-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((R)-tetrahydro-2H-pyran-3-yl)-1,4-dihydroimidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-4,5-dihydro-1l2,2l4-pyrazol-3-methamide (isomer 2); 1-Ethyl-N-((S)-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-(oxecyclobutane-3-yl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1H-pyrazole-5-methylamine;1-Ethyl-N-((S)-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-(oxacyclobutane-3-ylmethyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1H-pyrazol-5-methylamine; N-((S)-(3-(1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-2-ethyl-4H-2l4-pyrazol-3-methylamine; N-((S)-(3-((S)-1,1-dioxo-tetrahydrothiophene-3-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-methamide (isomer 1); N-((S)-(3-((S)-1,1-dioxo-tetrahydrothiophene-3-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazine-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-methamide (isomer 2); 1-Ethyl-N-((1S)-(3-(1-methyl-1-oxo-ionophosphacyclohexane-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1H-pyrazole-5-methamide (isomer 1); 1-Ethyl-N-((1S)-(3-(1-methyl-1-oxo-ionophosphacyclohexane-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1H-pyrazole-5-methamide (isomer 2); N-((S)-(3-((S)-2,2-dimethyl-1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxy-hexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-methamide (isomer 1);N-((S)-(3-((S)-2,2-dimethyl-1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxy-hexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-ethyl-1H-pyrazol-5-methamide (isomer 2); N-((S)-(3-(1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-4-methyl-1l3,2l2,5-oxadiazol-3-methamide; N-((S)-(3-((R)-2,2-dimethyl-1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxy-hexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazine-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-4-methyl-1,2,5-oxadiazol-3-methamide (isomer 1); N-((S)-(3-((R)-2,2-dimethyl-1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-4-methyl-1,2,5-oxadiazol-3-methamide (isomer 2); N-((S)-(3-(1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-4-ethyl-1,2,5-oxadiazol-3-methamide; N-((S)-(3-((S)-2,2-dimethyl-1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazine-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-4-ethyl-1,2,5-oxadiazol-3-methamide (isomer 1);N-((S)-(3-((S)-2,2-dimethyl-1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxy-hexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazine-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-4-ethyl-1,2,5-oxadiazol-3-methamide (isomer 2); 4-Cyclopropyl-N-((1S)-(3-(1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)octahydroimidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-2,5-dihydro-1,2,5-oxadiazol-3-methamide; 1-Ethyl-N-((S)-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-(oxacyclobutane-3-ylmethyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1H-1,2,4-triazol-5-methamide; N-((S)-((S)-3,3-difluorocyclohexyl)(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((S)-tetrahydrofuran-3-yl)-1,4-dihydroimidazo[1,2-b][1,2,4]triazine-6-yl)methyl)-1-methyl-1H-pyrazole-5-methamide (isomer 1); N-((S)-((S)-3,3-difluorocyclohexyl)(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((S)-tetrahydrofuran-3-yl)-1,4-dihydroimidazo[1,2-b][1,2,4]triazin-6-yl)methyl)-1-methyl-1H-pyrazol-5-methamide (isomer 2); 2-Methyl-N-((S)-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((R)-tetrahydrofuran-3-yl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1S,3R)-3-methylcyclohexyl)methyl)-4H-2l4-pyrazol-3-methamide (isomer 1); 2-Methyl-N-((S)-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((R)-tetrahydrofuran-3-yl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1S,3R)-3-methylcyclohexyl)methyl)-4H-2l4-pyrazol-3-methamide (isomer 2);N-((S)-(3-isopropyl-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1S,3R)-3-methylcyclohexyl)methyl)-1-methyl-1H-pyrazole-5-carboxamide; 4-cyclopropyl-N-((S)-(3-(1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1S,3R)-3-methylcyclohexyl)methyl)-1,2,5-oxadiazol-3-carboxamide; 1-Methyl-N-((S)-1-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((R)-tetrahydrofuran-3-yl)imidazo[1,2-b][1,2,4]triazin-6-yl)-3-(1-(trifluoromethyl)cyclopropyl)propyl)-1H-pyrazole-5-methamide (isomer 1); 1-Methyl-N-((S)-1-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((R)-tetrahydrofuran-3-yl)imidazo[1,2-b][1,2,4]triazin-6-yl)-3-(1-(trifluoromethyl)cyclopropyl)propyl)-1H-pyrazole-5-methamide (isomer 2); 4-Cyclopropyl-N-((R)-1-((R)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((R)-tetrahydrofuran-3-yl)-3,4-dihydroimidazo[1,2-b][1,2,4]triazin-6-yl)-2-((1,1,1-trifluoro-2-methylpropane-2-yl)oxy)ethyl)-1,2,5-oxadiazol-3-methamide (isomer 1); 4-Cyclopropyl-N-((R)-1-((R)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((R)-tetrahydrofuran-3-yl)-3,4-dihydroimidazo[1,2-b][1,2,4]triazin-6-yl)-2-((1,1,1-trifluoro-2-methylpropane-2-yl)oxy)ethyl)-1,2,5-oxadiazol-3-methamide (isomer 2); 4-Cyclopropyl-N-((R)-1-(3-(1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)-2-((1,1,1-trifluoro-2-methylpropane-2-yl)oxy)ethyl)-1,2,5-oxadiazol-3-methamide;N-((R)-1-(3-(1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)-2-((1,1,1-trifluoro-2-methylpropane-2-yl)oxy)ethyl)-4-ethyl-1,2,5-oxadiazol-3-methamide; N-((1S)-(3-(1-(cyanoimino)-1-oxo-ion-hexahydro-1l6-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-methamide (isomer 2); N-((1S)-(3-(1-(cyanoimino)-1-oxo-ion-hexahydro-1l6-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-methamide (isomer 2); 4-Cyclopropyl-N-((1S)-(4,4-difluorocyclohexyl)(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-(tetrahydrofuran-3-yl)imidazo[1,2-b][1,2,4]triazin-6-yl)methyl)-1,2,5-oxadiazol-3-carboxamide (isomer 1); 4-Cyclopropyl-N-((1S)-(4,4-difluorocyclohexyl)(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-(tetrahydrofuran-3-yl)imidazo[1,2-b][1,2,4]triazin-6-yl)methyl)-1,2,5-oxadiazol-3-carboxamide (isomer 2); 4-Cyclopropyl-N-((S)-(4,4-difluorocyclohexyl)(3-(1,1-dioxo-tetrahydro-2H-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)methyl)-1,2,5-oxadiazol-3-methamide; 4-Ethyl-N-((1R)-1-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-(tetrahydrofuran-3-yl)imidazo[1,2-b][1,2,4]triazin-6-yl)-2-((1,1,1-trifluoro-2-methylpropane-2-yl)oxy)ethyl)-1,2,5-oxadiazol-3-methamide (isomer 1);4-Ethyl-N-((1R)-1-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-(tetrahydrofuran-3-yl)imidazo[1,2-b][1,2,4]triazin-6-yl)-2-((1,1,1-trifluoro-2-methylpropane-2-yl)oxy)ethyl)-1,2,5-oxadiazol-3-methamide (isomer 2); N-((S)-(3-((2R,6R)-2,6-dimethylmorpholino)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-methyl-1H-pyrazol-5-methamide; N-((S)-(3-((2S,6S)-2,6-dimethylmorpholino)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-1,4-dihydroimidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-methyl-1H-pyrazol-5-methamide; N-((S)-(3-((2R,6S)-2,6-dimethylmorpholino)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-methyl-1H-pyrazol-5-methamide; N-((1S)-(3-(6-oxa-3-azabicyclo[3.1.1]heptane-3-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-1,4-dihydroimidazo[1,2-b][1,2,4]triazine-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-methyl-1H-pyrazole-5-methamide; N-((S)-(3-((1R,5S)-8-oxa-3-azabicyclo[3.2.1]octane-3-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-1,4-dihydroimidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-methyl-1H-pyrazole-5-methamide; 1-Methyl-N-((S)-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((R)-2-methylmorpholinyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1H-pyrazol-5-methamide;N-((S)-(3-((2R,6R)-2,6-dimethylmorpholino)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-isopropyl-1H-1,2,4-triazol-5-methamide; N-((S)-(3-((2R,6R)-2,6-dimethylmorpholinyl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-(2-fluoroethyl)-1H-pyrazole-5-methylamine; N-((S)-(4,4-difluorocyclohexyl)(3-((2S,6S)-2,6-dimethylmorpholinyl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)methyl)-1-ethyl-1H-1,2,4-triazin-5-methylamine; N-((S)-((S)-3,3-difluorocyclohexyl)(3-((2R,6R)-2,6-dimethylmorpholinyl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)methyl)-1-ethyl-1H-1,2,4-triazol-5-methamide; N-((S)-((S)-3,3-difluorocyclohexyl)(3-((2R,6R)-2,6-dimethylmorpholinyl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)methyl)-1-isopropyl-1H-1,2,4-triazol-5-methylamine; N-((S)-((S)-3,3-difluorocyclohexyl)(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-morpholinylimidazo[1,2-b][1,2,4]triazin-6-yl)methyl)-1-isopropyl-1H-1,2,4-triazol-5-methylamine; N-((S)-(3-((2R,6R)-2,6-dimethylmorpholino)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-1,4-dihydroimidazo[1,2-b][1,2,4]triazin-6-yl)((1S,3R)-3-methylcyclohexyl)methyl)-1-methyl-1H-pyrazol-5-methamide;N-((S)-(3-((2R,6R)-2,6-dimethylmorpholino)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-1,4-dihydroimidazo[1,2-b][1,2,4]triazine-6-yl)((1S,3R)-3-methylcyclohexyl)methyl)-1-isopropyl-3H-1l4,2,4-triazol-5-methamide; N-((1S)-1-(3-((2R,6R)-2,6-dimethylmorpholino)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3,4,4a,5-tetrahydroimidazo[1,2-b][1,2,4]triazin-6-yl)-3-(1-(trifluoromethyl)cyclopropyl)propyl)-1-methyl-1H-pyrazol-5-methamide; N-((S)-1-(3-((2R,6S)-2,6-dimethylmorpholino)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)-3-(1-(trifluoromethyl)cyclopropyl)propyl)-1-ethyl-1H-pyrazol-5-methylamine; 1-Ethyl-N-((S)-1-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-(4-oxa-7-azaspiro[2.5]octane-7-yl)imidazo[1,2-b][1,2,4]triazin-6-yl)-3-(1-(trifluoromethyl)cyclopropyl)propyl)-1H-pyrazole-5-methylamine; N-((S)-1-(3-((2R,6R)-2,6-dimethylmorpholinyl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)-3-(1-(trifluoromethyl)cyclopropyl)propyl)-1-(2-fluoroethyl)-1H-pyrazol-5-methylamine; 1-methyl-N-((S)-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((S)-2-methylmorpholinyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1H-pyrazol-5-methylamine; N-((1S)-(3-(6-oxa-3-azabicyclo[3.1.1]heptane-3-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazine-6-yl)(cyclohexyl)methyl)-1-methyl-1H-pyrazole-5-methamide;N-((S)-(3-((1R,5S)-8-oxa-3-azabicyclo[3.2.1]octane-3-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)(cyclohexyl)methyl)-1-methyl-1H-pyrazol-5-carboxamide; N-((S)-cyclohexyl(3-((2R,6R)-2,6-dimethylmorpholinyl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)methyl)-1-methyl-1H-pyrazol-5-carboxamide; N-((S)-cyclohexyl(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((R)-2-methylmorpholinyl)imidazo[1,2-b][1,2,4]triazin-6-yl)methyl)-1-methyl-1H-pyrazol-5-methylamine; N-((S)-cyclohexyl(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((S)-2-methylmorpholinyl)imidazo[1,2-b][1,2,4]triazin-6-yl)methyl)-1-methyl-1H-pyrazol-5-methylamine; N-((1S)-(3-(1-(cyanoimino)hexahydro-1l4-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-ethyl-1H-pyrazole-5-methylamine; 4-Ethyl-N-((S)-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((R)-tetrahydrofuran-3-yl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1,2,5-oxadiazol-3-methamide (isomer 1); 4-Ethyl-N-((S)-(2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)-3-((R)-tetrahydrofuran-3-yl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1,2,5-oxadiazol-3-carboxamide (isomer 2); N-((S)-(4,4-difluorocyclohexyl)(3-isopropyl-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)methyl)-1-ethyl-1H-pyrazole-5-carboxamide (isomer 1);N-((S)-(4,4-difluorocyclohexyl)(3-isopropyl-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)methyl)-1-ethyl-1H-pyrazol-5-carboxamide (isomer 2); N-((S)-(3-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptane-5-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)(cyclohexyl)methyl)-1-methyl-1H-pyrazol-5-carboxamide; N-((S)-(3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane-5-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-methyl-1H-pyrazol-5-methamide; N-((S)-(3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane-5-yl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)(cyclohexyl)methyl)-1-methyl-1H-pyrazol-5-methylamine; N-((1S)-(3-((1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptane-5-yl)-2-(((5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1-methyl-1H-pyrazol-5-methylamine; 1-Ethyl-N-((S)-(3-(1-imino-1-oxo-iono-hexahydro-1l6-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxy-hexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1H-pyrazole-5-methamide (isomer 1); 1-Ethyl-N-((S)-(3-(1-imino-1-oxo-iono-hexahydro-1l6-thiopyran-4-yl)-2-(((3R,5S)-5-methyl-2-sideoxy-hexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((1r,4S)-4-methylcyclohexyl)methyl)-1H-pyrazole-5-methamide (isomer 2);N-((S)-((S)-3,3-difluorocyclohexyl)(3-((2R,6R)-2,6-dimethylmorpholinyl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)methyl)-4-methyl-1,2,5-oxadiazol-3-methoxyamine; and N- ((S)-(3-((2R,6R)-2,6-dimethylmorpholinyl)-2-(((3R,5S)-5-methyl-2-sideoxyhexahydropyridin-3-yl)methyl)imidazo[1,2-b][1,2,4]triazin-6-yl)((S)-8-fluoro-1,2,3,4-tetrahydronaphthyl-2-yl)methyl)-1-methyl-1H-pyrazole-5-methamide; or a pharmaceutically acceptable salt thereof.

19. A pharmaceutical composition comprising a compound of any one of claims 1 to 18 or a pharmaceutically acceptable salt, stereoisomer or hydrate thereof, and a pharmaceutically acceptable carrier, diluent or excipient.

20. Use of a compound of any one of claims 1 to 18, or a pharmaceutically acceptable salt, stereoisomer, or hydrate thereof, for the manufacture of an agent for the treatment of psoriasis.

21. Use of a compound as claimed in claim 18 or a pharmaceutically acceptable salt, stereoisomer, or hydrate thereof for the manufacture of an agent for the treatment of psoriasis.

22. Use of a compound of any one of claims 1 to 18, or a pharmaceutically acceptable salt, stereoisomer, or hydrate thereof, for the manufacture of an agent for the treatment of diseases or conditions selected from the group consisting of: psoriasis, plaque psoriasis, guttate psoriasis, skinfold psoriasis, pustular psoriasis, erythrodermic psoriasis, palmoplantar psoriasis, rheumatoid arthritis, multiple sclerosis, systemic sclerosis, psoriatic arthritis, axial spondylitis, adhesive capsulitis, hidradenitis suppurativa, systemic lupus erythematosus, palmoplantar pustulosis (PPP), atopic dermatitis, asthma, non-infectious uveitis, and COPD.