PROTEASE INHIBITORS

摘要

The present invention provides compounds of Formula (I) wherein X, X1, X2, and X3 are independently selected from -H, -C1-6alkyl, -C1-6alkyl substituted by 1-3 fluorines, -C3-7cycloalkyl, -CN, -C(O)R1, -C(O)OR1, -C(O)NR1R2, -C(NR1)NR1R2, -C(NCN)NR1R2, -C(NCN)SR3, -NO2, -NR1SO2R3, -NR1C(O)R1, -NR1R2, -NR1(C=NR1)NR1R2, -NR1C(O)NR1R2, -NR1C(O)R1, -NR1C(O)OR3, -NR1C(NCN)SR3, -NR1C(NCN)NR1R2, -NR1C(O)C(O)NR1R2, -NR1C(O)C(O)R2, -Cl, -Br, -I, -F, -OR1, -O(CH2)qOR3, -O(CH2)2OH, -OC(O)R1, -O(CH2)qC(O)NR1R2, -O(CH2)qC(O)R1, -SR1, -SO2NR1R2 or -S(O)mR3; m is 0, 1 or 2; q is 1 or 2; n is 0 to 2; R1 is -H, -C1-6alkyl, -CF3 or -CH2CF3; or when R1 and R2 are taken together as NR1R2, they may together with the nitrogen form a 5 to 7 membered ring comprised of carbon or carbon and one or more additional heteroatoms selected from O, N, or S; R2 is H, -C1-6alkyl, -CF3 or -CH2CF3; R3 is -C1-6alkyl, -CF3 or -CH2CF3; and X4 is -H, -C1-6alkyl, -C3-7cycloalkyl, -COAr, -COOC1-6alkyl, or COOAr; which inhibit proteases, including cathepsin K, pharmaceutical compositions of such compounds, and methods for treating diseases of excessive bone loss or cartilage or matrix degradation, including osteoporosis; gingival disease including gingivitis and periodontitis; arthritis, more specifically, osteoarthritis and rheumatoid arthritis; Paget's disease; hypercalcemia of malignancy; and metabolic bone disease therewith.