Trifluoromethylketone derivatives, processes for preparation...

Details Trifluoromethylketone derivatives, processes for preparation... Trifluoromethylketone derivatives, processes for preparation...

C - Chemistry, Metallurgy

07

K

C07K 5/062 (2006.01) C07K 5/06 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2058560

There are described trifluoromethylketone derivatives of the following formula: (see formula I) wherein R1 is lower alkyl which has one or two substituents selected from carboxy, esterified carboxy and di-lower alkylcarbamoyl; phenyl(lower)alkyl, the phenyl moiety of which may have halogen or nitro or amino and the alkyl moiety of which may have carboxy or esterified carboxy; halo-phenyl; morpholino; or morpholino(lower)alkyl, R2 and R3 are each lower alkyl, X is - or -NH-, and Y is (see formula II) or (see formula III)~~~ and pharmaceutically acceptable salts thereof. These derivatives have a human leukocyte elastase-inhibiting activity and are useful as human leukocyte elastase inhibitors for treating or preventing degenerative diseases, for example, pulmonary emphysema, atherosclerosis, rheumatoid arthritis, arthrosclerosis, osteoarthritis, psoriasis, pancreatitis, periodontosis, pulmonary fibrosis. Cystic fibrosis, chronic bronchitis, bronchiectasia, diffuse panbronchiolitis, respiratory injury, adult respiratory distress syndrome and the like. They are also useful for the treatment or prevention of asthma, graft rejection nephritis, hydroa, disseminated intravascular coagulation, shock, systemic lupus erythematosus, clone disease, ischemia-reperfusion injury, chronic obstructive pulmonary disease (COPD), premature rupture of the membrane (PROM), corneal sarring or fibroblast proliferation (ocular coagulation, burns, mechanical and chemical injury, kerato-conjunctivitis, etc.), and sepsis. The preparation of these derivatives is also disclosed as well as pharmaceutical compositions containing them, and their use in the above treatments.

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