The invention relates to 4-phenyl-6-substituted-pyrimidine-2-carbonitrilederivatives having Formula (I) wherein R represents 1-3 optional substituentsindependently selected from (C1-4)- alkyl (optionally substituted with one ormore halogens), (C1-4)alkyloxy (optionally substituted with one or morehalogens) 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 or2 heteroatoms selected from O, S and NR4, and a 5 or 6-membered aromaticheterocyclic group comprising 1-4 N atoms； or R1 and Y form together with thenitrogen to which they are bonded a 5-8 membered saturated heterocyclic ring,optionally comprising a further heteroatom selected from O, S, NR4 and NO； thering being optionally substituted with NR2R3 or with 1 to 4 (C1-3)alkylgroups； R2 and R3 are independently H or (C1-4)alkyl； or R2 and R3 formtogether with the nitrogen to which they are bonded a 4-8 membered saturatedheterocyclic 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)alkyl or carboxy(C1-4)alkyl； or a pharmaceuticallyacceptable 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 treatmentof cathepsin K and cathepsin S related disorders, e.g. osteoporosis,atherosclerosis, inflammation and immune disorders such as rheumatoidarthritis and chronic pain.
