MACROCYCLIC KETOAMIDE IMMUNOPROTEASOME INHIBITORS

摘要

The invention is concerned with the compounds of formula (I):;;and pharmaceutically acceptable salts thereof, wherein X, Y, Z, R1, R2, R3 and R3′ are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of formula I as well as pharmaceutical compositions containing such compounds. The compounds of formula I are LMP7 inhibitors and may be useful in treating associated inflammatory diseases and disorders such as, for example, rheumatoid arthritis, lupus and irritable bowel disease.

主权项

1. A compound of formula (I): wherein: X is CH2, 0 or NH; Y is CH or N; Z is CH or N; R1 is C1-7 alkyl, C3-8 cycloalkyl or —CH2-phenyl; R2 is C1-7 alkyl or —CH2-phenyl; and one of R3 or R3′ is hydrogen and the other is C3-8 cycloalkyl, unsubstituted C1-7 alkyl or C1-7 alkyl substituted with C1-7 alkoxy, or
R3 and R3′, together with the carbon atom to which they are attached, combine to form a C3-8 cycloalkyl moiety, or a pharmaceutically acceptable salt thereof.