Patent ID: 6403581
Filing Date: 2002-06-11
Classification: A61K

Abstract:
A method of treating, inhibiting or controlling a ras-associated disease by inhibiting farnesyl-protein transferase(FPTase) enzyme in a mammal in need thereof, which comprises administering to said mammal an effective amount of a compound of Formula I: wherein:the dotted line ------ at position a is an optional additional bond; the dotted line ------ at position b is an optional additional bond; R1 is selected from the group consisting of H, alkyl of 1 to 6 carbon atoms, phenyl, and a moiety of the following: R1a is selected from alkoxy of 1 to 8 carbon atoms, trifluoromethyl and halogen; c is an integer of 0 to 3; d is an integer of 1 to 3; n is an integer of 1 to 6; A is a monocyclic ring having 5 or 6 ring atoms optionally having saturated or unsaturated bonds and containing 1 or 2 nitrogen atoms and 0 or 1 oxygen atoms; R2 is selected from the group consisting of hydrogen, alkoxy of 1 to 8 carbon atoms, alkylthio of 1 to 8 carbon atoms, alkylsulfonyl of 1 to 8 carbon atoms, arylsulfonyl of 6 to 12 carbon atoms, hydroxy, hydroxyalkyl of 1 to 8 carbon atoms, mercapto, alkylcarbonyloxy of 1 to 8 carbon atoms, amino, mono(alkyl)amino of 1 to 8 carbon atoms, di(alkyl)amino of 1 to 16 carbon atoms, (alpha, omega-alkylene)amino of 2 to 8 carbon atoms, alkyl of 1 to 8 carbon atoms, arylalkyl of 7 to 20 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, cycloalkylalkoxy of 3 to 10 carbon atoms, alkylcarbonyl of 1 to 8 carbon atoms, arylcarbonyl of 6 to 12 carbon atoms, cyano, sulfonamido, N-alkylsulfonamido of 1 to 8 carbon atoms, N,N-(dialkyl)sulfonamido of 2 to 16 carbon atoms, alpha-hydroxyalkyl of 1 to 8 carbon atoms, alpha-aminoalkyl of 1 to 8 carbon atoms, alpha-alkylaminoalkyl of 2 to 16 carbon atoms, alpha-(dialkyl)amino(alkyl) of 3 to 24 carbon atoms, carboxamido, N-(alkyl)carboxamido of 1 to 8 carbon atoms, N,N-(dialkyl)carboxamido of 2 to 16 carbon atoms, and halogen; Q is selected from a) a chain â€”(CH2)mâ€” optionally containing one or more â€”CH&boxH;CHâ€” or â€”Câ‰¡Câ€” linkages and further optionally replacing one of the chain â€”CH2â€” groups with â€”Oâ€”, â€”Sâ€”, â€”SO2â€”, â€”NHâ€”, â€”N-alkyl of 1 to 8 carbon atoms, â€”N-aryl of 6 to 12 carbon atoms, or â€”(C&boxH;O)NHâ€” and further optionally substituting said chain with substitutents selected from alkyl of 1 to 8 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, arylalkyl of 7 to 20 carbon atoms, aryl of 6 to 12 carbon atoms, hydroxy, alkoxy of 1 to 8 carbon atoms, and fluoro; or b) a moiety of the formula c) a moiety of the formula k, 1 and m are independently selected from an integer of 1 to 12; B is a monocyclic ring having 3 to 10 ring atoms; R3 is selected from hydrogen, and a substituted or unsubstituted heterocycle; R4 is selected from hydrogen, halogen, and alkyl of 1 to 6 carbon atoms; R5 is selected from hydrogen and alkyl of 1 to 8 carbon atoms; R5 and Q taken together with the nitrogen atom to which they are attached form a monocyclic ring having the moiety provided that at either position a or b is present an additional bond and if at b, is present an additional bond, R1 is not present and a is not present, and if at a, is present an additional bond, R5 is not present and b is not present; or a pharmaceutically acceptable salt thereof.