Farnesyl protein transferase inhibitors for treating arthropathies

摘要

A farnesyl protein transferase inhibitor of a compound of formula (I), or a compound of formula (II) or (III) which is metabolized in vivo to a compound of formula (I) is used in the manufacture of a medicament for treating arthropathies. The farnesyl protein transferase inhibitor can be in the form of a stereoisomeric form thereof, a pharmaceutically acceptable acid or base addition salt thereof. In formula (I), (II) and (III): the dotted line represents an optional bond; X is oxygen or sulphur; R1 is hydrogen, alkyl, Ar1, Ar2-alkyl, quinolinylalkyl, pyridylalkyl, hydroxyalkyl, alkyloxyalkyl, mono- or di- alkyl aminoalkyl, aminoalkyl, or -Alk1-C(=O)-R9, -Alk1-S(O)- R9 or -Alk1-S(O)2-R9; Alk1 is alkanediyl; R2, R3 and R16 are independently hydrogen, hydroxy, halo, cyano, alkyl, alkyloxy, hydroxyalkyloxy, alkyloxyalkyloxy, aminoalkyloxy, mono- or di-alkyl aminoalkyloxy, Ar1, Ar2- alkyl, Ar2-oxy, Ar2-alkyloxy, hydroxycarbonyl, alkyloxycarbonyl, trihalomethyl, trihalomethoxy, alkenyl, 4,4-dimethyloxazolyl; or when on adjacent positions R2 and R3 taken together may form a bivalent radical of formula -O- CH2-O-, -O-CH2-CH2-O-, -O-CH=CH-, -O-CH2-CH2-, -O-CH2-CH2- CH2-, or -CH=CH-CH=CH-; R4 and R5 independently are hydrogen, halo, Ar1, alkyl, hydroxyalkyl, alkyloxyalkyl, alkyloxy, alkylthio, amino, hydroxycarbonyl, alkyloxycarbonyl, alkyl-S(O)-alkyl or alkyl-S(O)2-alkyl; R6 and R7 independently are hydrogen, halo, cyano, alkyl, alkyloxy, Ar2-oxy, trihalomethyl, alkylthio, di-alkyl amino, or when on adjacent positions R6 and R7 taken together may form a bivalent radical of formula -O-CH2-O- or -CH=CH-CH=CH-; R8 is hydrogen, alkyl, cyano, hydroxycarbonyl, alkyloxycarbonyl, alkylcarbonylalkyl, cyanoalkyl, alkyloxycarbonylalkyl, carboxyalkyl, hydroxyalkyl, aminoalkyl, mono- or di-alkyl-aminoalkyl, imidazolyl, haloalkyl, alkyloxy-alkyl, aminocarbonylalkyl or -O-R10, -S- R10, -N-11R12, R9 to R12 are as defined in the specification; R17 is hydrogen, halo, cyano, alkyl, alkyloxycarbonyl or Ar1; R18 is hydrogen, alkyl, alkyloxy or halo; R19 is hydrogen or alkyl and Ar1 and Ar2 are independently optionally substituted phenyl.