Methods for treating proliferative diseases
AssigneeSchering Corporation
InventorsWalter R. Bishop, Joseph J. Catino, Ronald J. Doll, Ashit Ganguly, Viyyoor M. Girijavallabhan, Paul Kirschimeier, Ming Liu, Loretta L. Nielsen, David L. Cutler
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Abstract
Methods are provided for treating proliferative diseases, especially cancers, comprising administering (1) a farnesyl protein transferase inhibitor in conjunction with (2) an antineoplastic agent and/or radiation therapy.
Claims24
A method of treating a proliferative disease in a patient in need of such treatment, said treatment comprising administering, concurrently or sequentially, an effective amount of (1) a FPT inhibitor and (2) an antineoplastic agent and/or radiation therapy;
- wherein the FPT inhibitor comprises a compound having the formula (I) or (III):
- where,
- X1, X2 and X3, independently of one another, are each a hydrogen, chlorine or bromine atom;
- the dotted line between Z and the 7-membered carbocyclic ring represents a single or double bond;
- Z is a nitrogen atom or a CH radical when the bond between Z and the 7-membered carbocyclic ring is a single bond;
- Z is a C radical when the bond between Z and the 7-membered carbocyclic ring is a double bond;
- Y1=
- where R1 is a hydrogen atom or a lower alkyl, —CONH2 or —COR2 group, where R2 is a lower alkyl group, or
- Y1=
- or one of its isomers in the 1, 2 or 3 position;
- R6 is a —NR7(CH2)n—R4 group, where n is 2 or 3;
- R4 is a
- group attached at the 1, 2, 4 or 5 position, where R5 is a hydrogen atom or a lower alkyl group;
- and R7 is a hydrogen atom or an alkyl group substituted with a phenyl group, or
- R6 is
- where R4 is defined the same as above;
- and
- Y2 is a X6-cycloalkyl group, where X6 is a CH2, O or NH group;
- with the proviso that the FPT inhibitor is not the following compound:
The method of claim 50 wherein the FPT inhibitor is a compound having the formula (III):
- where,
- X1, X2, X3, Y2 and R6 are defined the same as above.
A method of treating a proliferative disease in a patient in need of such treatment, said treatment comprising administering, concurrently or sequentially, an effective amount of (1) a FPT inhibitor and (2) gemcitabine;
- wherein the FPT inhibitor is a compound having the formula (I) or (III):
- where,
- X1, X2 and X3, independently of one another, are each a hydrogen, chlorine or bromine atom;
- the dotted line between Z and the 7-membered carbocyclic ring represents a single or double bond;
- Z is a nitrogen atom or a CH radical when the bond between Z and the 7-membered carbocyclic ring is a single bond;
- Z is a C radical when the bond between Z and the 7-membered carbocyclic ring is a double bond;
- Y1=
- where R1 is a hydrogen atom or a lower alky, —CONH2 or —COR2 group, where R2 is a lower alkyl group, or
- Y1=
- or one of its isomers in the 1, 2 or 3 position;
- R6 is a —NR7(CH2)n—R4 group, where n is 2 or 3;
- R4 is a
- group attached at the 1, 2, 4 or 5 position, where R5 is a hydrogen atom or a lower alkyl group;
- and R7 is a hydrogen atom or an alkyl group substituted with a phenyl group, or
- R6 is
- where R4is defined the same as above;
- and
- Y2 is a X6-cycloalkyl group, where X6 is a CH2, O or NH group;
- with the proviso that the FPT inhibitor is not the following compound:
Dependencies are inferred from the claim text.