Squaramide derivatives as CXCR2 antagonist
The present invention relates to compounds of formula (I) wherein X, R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein, which are useful for treating diseases which respond to CXCR2 receptor mediators. Pharmaceutical compositions that contain the compounds and processes for preparing the compounds are also described.
1. The compound which is selected from the group consisting of:
Structure
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein the compound is 6-chloro-2-hydroxy-N-methoxy-N-methyl-3-{2-[(R)-1-(5-methyl-furan-2-yl)-propylamino]-3,4-dioxo-cyclobut-1-enyl amino}-benzenesulfonamide, or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , wherein the compound is 6-chloro-3-{3,4-dioxo-2-[(R)-1-(tetrahydro-furan-2-yl)-propylamino]-cyclobut-1-enylamino}-2-hydroxy-N-methoxy-N-methyl-benzenesulfonamide, or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 , wherein the compound is 6 chloro-2-hydroxy-N-methoxy-N-methyl-3-{2-[(R)-1-((2R,5R)-5-methyl-tetrahydro-furan-2-yl)-propylamino]-3,4-dioxo-cyclobut-1-enylamino}-benzenesulfonamide, or a pharmaceutically acceptable salt thereof.
5. The compound of claim 1 , wherein the compound is 6-chloro-3-[3,4-dioxo-2-((R)-1-pyridin-2-yl-propylamino)-cyclobut-1-enylamino]-2-hydroxy-N-methoxy-N-methyl-benzenesulfonamide, or a pharmaceutically acceptable salt thereof.
6. The compound of claim 1 , wherein the compound is 6-chloro-3-[2-(1-ethyl-propylamino)-3,4-dioxo-cyclobut-1-enylamino]-2-hydroxy-N-methoxy-N-methyl-benzenesulfonamide, or a pharmaceutically acceptable salt thereof.
7. The compound of claim 6 , wherein the compound is the choline salt.
8. The compound of claim 1 , wherein the compound is 6 chloro-3-{3,4-dioxo-2-[(R)-1-(tetrahydro-furan-2-yl)-propylamino]-cyclobut-1-enylamino}-N-ethyl-2-hydroxy-N-methoxy-benzenesulfonamide, or a pharmaceutically acceptable salt thereof.
9. The compound of claim 1 , wherein the compound is 6-chloro-N-ethyl-2-hydroxy-3-(2-(isopropylamino)-3,4-dioxocyclobut-1-enylamino)-N-methoxybenzenesulfonamide, or a pharmaceutically acceptable salt thereof.
10. The compound of claim 1 , wherein the compound is 3-(4-chloro-2-hydroxy-3-((S)-4-hydroxyisoxazolidin-2-ylsulfonyl)phenylamino)-4-((R)-1-((2R,5R)-5-methyltetrahydrofuran-2-yl)propylamino)cyclobut-3-ene-1,2-dione, or a pharmaceutically acceptable salt thereof.
11. The compound of claim 1 , wherein the compound is 6-chloro-2-hydroxy-3-(2-(isopropylamino)-3,4-dioxocyclobut-1-enylamino)-N-methoxy-N-methylbenzenesulfonamide, or a pharmaceutically acceptable salt thereof.
12. The compound of claim 1 , wherein the compound is (R)-6-chloro-N-ethyl-2-hydroxy-N-methoxy-3-(2-(1-(5-methylfuran-2-yl)propylamino)-3,4-dioxocyclobut-1-enylamino)benzenesulfonamide, or a pharmaceutically acceptable salt thereof.
13. The compound of claim 1 , wherein the compound is 6-chloro-3-(2-(heptan-4-ylamino)-3,4-dioxocyclobut-1-enylamino)-2-hydroxy-N-methoxy-N-methylbenzenesulfonamide, or a pharmaceutically acceptable salt thereof.
14. The compound of claim 1 , wherein the compound is 6-chloro-3-(2-(cyclopentylamino)-3,4-dioxocyclobut-1-enylamino)-2-hydroxy-N-methoxy-N-methylbenzenesulfonamide, or a pharmaceutically acceptable salt thereof.
15. The compound of claim 1 , wherein the compound is 3-(3,4-dioxo-2-((R)-1-((S)-tetrahydrofuran-2-yl)propylamino)cyclobut-1-enylamino)-N-ethyl-2-hydroxy-N-methoxybenzenesulfonamide, or a pharmaceutically acceptable salt thereof.
16. A pharmaceutical composition, comprising:
the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier or excipient.