| 摘要 |
The invention relates to 4-phenyl-6-substituted-pyrimidine-2-carbonitrile derivatives having Formula (I) wherein R represents 1-3 optional substituents independently selected from (C1-4)- alkyl (optionally substituted with one or more halogens), (C1-4)alkyloxy (optionally substituted with one or more halogens) and halogen; X is NR1, O or S; R1 is H or (C1-4)alkyl; Y is (C1- 4)alkyl, benzyl or (C2-6)alkyl, substituted with a group selected from OH, (C1- 4)alkyloxy, NR2R3, a 4-8 membered saturated heterocyclic ring comprising 1 or 2 heteroatoms selected from O, S and NR4, and a 5 or 6-membered aromatic heterocyclic group comprising 1-4 N atoms; or R1 and Y form together with the nitrogen to which they are bonded a 5-8 membered saturated heterocyclic ring, optionally comprising a further heteroatom selected from O, S, NR4 and NO; the ring being optionally substituted with NR2R3 or with 1 to 4 (C1-3)alkyl groups; R2 and R3 are independently H or (C1-4)alkyl; or R2 and R3 form together with the nitrogen to which they are bonded a 4-8 membered saturated heterocyclic ring, optionally comprising a further heteroatom selected from O, S and NR4; R4 is H, (C1-6)alkyl,(C3-6) cycloalkyl, (C3-6)cycloalkyl(C1- 4)alkyl, (C1-4)alkyloxy-(C1-4)alkyl, benzyl, amido- (C1-4)alkyl, (C1- 6)alkyloxycarbonyl(C1-4)alkylor carboxy(C1-4)alkyl; or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising the same, as well as to the use of these 4-phenyl-6-substituted-pyrimidine-2- carbonitrile derivatives for the preparation of a medicament for the treatment of cathepsin K and cathepsin S related disorders, e.g. osteoporosis, atherosclerosis, inflammation and immune disorders such as rheumatoid arthritis and chronic pain.
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