Claims
- 1. A compound of Formula (I):
- 2. A compound of claim 1 wherein Y is aryl and X is —SO2— or a pharmaceutically acceptable salt thereof.
- 3. A compound of claim 2 wherein Y is phenyl or a pharmaceutically acceptable salt thereof.
- 4. A compound of claim 1 wherein Y is aryl and X is —SO2—, Z is oxygen and R4, R5 and R6 are hydrogen or a pharmaceutically acceptable salt thereof.
- 5. A compound of claim 4 wherein Y is phenyl or a pharmaceutically acceptable salt thereof.
- 6. A compound of claim 1 wherein Y is aryl and X is —SO2— and Z is oxygen, R4, R5 and R6 are hydrogen, R7 is hydrogen or methyl and R2 is isopropyl or a pharmaceutically acceptable salt thereof.
- 7. A compound of claim 6 wherein Y is phenyl or a pharmaceutically acceptable salt thereof.
- 8. A compound of claim 1 wherein Y is aryl and R1 and R3 together with the atoms to which each is attached form a thiomorpholine ring or a pharmaceutically acceptable salt thereof.
- 9. A compound of claim 8 wherein Y is phenyl or a pharmaceutically acceptable salt thereof.
- 10. A compound of claim 9 wherein the absolute stereochemistry is shown by the formula:
- 11. A compound of claim 1 selected from the group consisting of:
2-({[4-(2,3-Butadienyloxy)phenyl]sulfonyl}amino)-N-hydroxy-3-methylbutanamide, 2-[{[4-(2,3-Butadienyloxy)phenyl]sulfonyl}(methyl)amino]-N-hydroxy-3-methylbutanamide, N-Hydroxy-3-methyl-2-({[4-(2,3-pentadienyloxy)phenyl]sulfonyl}amino)butanamide, N-Hydroxy-3-methyl-2-(methyl{[4-(2,3-pentadienyloxy)phenyl]sulfonyl}amino)butanamide, (3S)-4-{[4-(2,3- Butadienyloxy)phenyl]sulfonyl}-N-hydroxy-2,2-dimethyl-3-thiomorpholinecarboxamide, (3S)-N-Hydroxy-2,2-dimethyl-4-{[4-(2,3-pentadienyloxy)phenyl]sulfonyl}-3-thiomorpholinecarboxamide, 1-Acetyl-4-{[4-(2,3-butadienyloxy)phenyl]sulfonyl}-N-hydroxy-2,3,4,5-tetrahydro-1H-1,4- benzodiazepine-3-carboxamide, 1-Benzoyl-4-(4-buta-2,3-dienyloxy-benzenesulfonyl)-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepine-3-carboxylic acid hydroxyamide and 1-Benzoyl-N-hydroxy-4-{[4-(2,3-pentadienyloxy)phenyl]sulfonyl}-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-3-carboxamide.
- 12. A method of treating a pathological condition mediated by TNF-α converting enzyme (TACE) in a mammal in need thereof which comprises administering to said mammal a therapeutically effective amount of a compound having the formula
- 13. The method of claim 12 wherein the condition treated is rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease, degenerative cartilage loss, graft rejection, cachexia, inflammation, fever, insulin resistance, septic shock, congestive heart failure, inflammatory disease of the central nervous system, inflammatory bowel disease or HIV.
- 14. A pharmaceutical composition comprising a compound having the formula
- 15. A method of treating a pathological condition mediated by matrix metalloproteinases in a mammal in need thereof which comprises administering to said mammal a therapeutically effective amount of a compound having the formula
- 16. The method of claim 15 wherein the condition treated is rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease, degenerative cartilage loss, graft rejection, cachexia, inflammation, fever, insulin resistance, septic shock, congestive heart failure, inflammatory disease of the central nervous system, inflammatory bowel disease or HIV.
- 17. A process for making intermediate compounds of the formula
- 18. The process of claim 17 wherein the strong base in step a is butyl lithium.
- 19. The process of claim 17 wherein the organic acid in step a is pyridinium p-toluenesulfonic acid.
- 20. The process of claim 17 wherein the hydride reagent in step b is lithium aluminum hydride.
- 21. The process of claim 17 wherein the alkali metal base in step d is sodium hydroxide.
- 22. The process of claim 17 wherein the chlorinating agent of step e is thionyl chloride, chlorosulfonic acid, oxalyl chloride or phosphorous pentachloride.
- 23. The process of claim 17 wherein the halogenating agent of step e is fluorosulfonic acid or thionyl bromide.
- 24. A process for preparing an allene of the formula:
- 25. The process of claim 24 wherein the strong base in step a is butyl lithium.
- 26. The process of claim 24 wherein the hydride reducing agent in step c is lithium aluminum hydride.
- 27. A process for preparing an allene of the formula:
- 28. A process for preparing a compound of Formula (I):
- 29. The process of claim 29 wherein the activating reagent is a chlorinating agent such as thionyl chloride, chlorosulfonic acid, oxalyl chloride, or phosphorous pentachloride, or other halogenating agents such as fluorosulfonic acid or thionyl bromide, a suitable peptide coupling reagent which include for example, but not limited to N,N′-Dicyclohexylcarbodiimide plus 1-hydroxybenzotriazole; Benzotriazol-1-yloxytris (dimethylamino)phosphonium hexafluorophosphate (BOP-reagent); N,N′-Bis[2-oxo-3-oxazolidinyl]phosphorodiamidic chloride (BOB-Cl); Diphenylphosphinyl chloride (DPP-Cl); Diethoxyphosphoryl cyanide; 2-Chloro-1-methylpyridinium iodide; or Phenyldichlorophosphate plus imidazole; or ethyl chloroformate.
- 30. A compound of the formula
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] “This application claims priority from copending provisional application serial No. 60/336,050 filed on Nov. 1, 2001, the entire disclosure of which is hereby incorporated by reference.”
Provisional Applications (1)
|
Number |
Date |
Country |
|
60336050 |
Nov 2001 |
US |