COMBINATIONS OF PYRAZOLE KINASE INHIBITORS AND FURTHER ANTITUMOR AGENTS

摘要

The invention provides a combination of a compound having the formula (0) and two or more further anti-cancer agents: or salts or tautomers or N-oxides or solvates thereof; wherein X is a group R<SUP>1</SUP>-A-NR<SUP>4</SUP>- or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO2, C=O, NR<SUP>9</SUP>(C=O) or 0(C=O) wherein R<SUP>9</SUP> is hydrogen or C<SUB>1-4</SUB> hydrocarbyl optionally substituted by hydroxy or C<SUB>1-4</SUB> alkoxy; Y is a bond or an alkylene chain of 1 , 2 or 3 carbon atoms in length; R<SUP>1</SUP> is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C<SUB>1-8</SUB> hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C<SUB>1-4</SUB> hydrocarbyloxy, amino, mono- or di-C<SUB>1-4</SUB> hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO<SUB>2</SUB>; R<SUP>2</SUP> is hydrogen; halogen; C<SUB>1-4</SUB> alkoxy (e.g. methoxy); or a C<SUB>1-4</SUB> hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C<SUB>1-4</SUB> alkoxy (e.g. methoxy); R<SUP>3</SUP> is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R<SUP>4 </SUP>is hydrogen or a C<SUB>1-4</SUB> hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C<SUB>1-4</SUB> alkoxy (e.g. methoxy).