Patent ID: 6784198
Filing Date: 2004-08-31
Classification: A61K,A61P,C07D

Abstract:
A method for the treatment of cell proliferative disorders associated with an altered cell dependent kinase activity, comprisingadministering to a mammal in need thereof a fixed dose combination product comprising (A) an effective amount of a compound represented by formula (I) or (II): wherein L is a phenyl group or a 5 or 6 membered aromatic heterocycle with one or more heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; R is (i) a halogen atom, a nitro group, or a group selected from the group consisting of pyrrolidino, morpholino, piperazino, N-alkyl piperazino, N-aryl-piperazino, N-arylalkyl-piperazino, piperidino and azabicyclo[3.2.2]nonane; or (ii) an amino group optionally further substituted with one or more groups, which may be the same or different, selected from the group consisting of alkyl, aryl, arylalkyl, alkylsulphonyl, arylsulphonyl, arylalkylsulphonyl, alkylcarbonyl, arylcarbonyl, and arylalkylcarbonyl, wherein the alkyl moieties therein are optionally further substituted with one or more hydroxy or amino groups; or (iii) a C3-C6 cycloalkyl optionally substituted with a straight or branched C1-C6 alkyl group; or (iv) a straight or branched C3-C6 alkyl group or an arylalkyl group which is optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, carboxy, hydroxy, nitro, alkylthio, alkoxy, straight or branched C1-C6 alkyl, arylthio, aryloxy, amino, alkylamino, dialkylamino, arylamino, arylalkylamino, hydroxyaminocarbonyl, alkoxyaminocarbonyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, alkyl-C3-C6 cycloalkyl, alkylcarbonyl, arylcarbonyl arylalkylcarbonyl, alkylsulphonyl, arylsulphonyl, arylalkylsulphonyl, aminosulphonyl, alkylaminosulphonyl, dialkylaminosulphonyl, alkylcarbonylamino, arylalkylcarbonylamino, arylaminosulphonyl, arylalkylaminosulphonyl, arylcarbonylamino, alkylsulphonylamino, arylsulphonylamino, arylalkylsulphonylamino, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, arylalkylaminocarbonyl, pyrrolidino, morpholino, piperazino, N-alkylpiperazino, N-aryl-piperazino, N-arylalkylpiperazino, piperidino, and azabicyclo[3.2.2]nonane; or (v) an aryl group which is optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, carboxy, hydroxy, nitro, alkylthio, alkoxy, straight or branched C1-C6 alkyl, arylthio, aryloxy, amino, alkylamino, dialkylamino, arylamino, arylalkylamino, hydroxyaminocarbonyl, alkoxyaminocarbonyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, alkyl-C3-C6 cycloalkyl, alkylcarbonyl, arylcarbonyl, arylalkylcarbonyl, alkylsulphonyl, arylsulphonyl, arylalkylsulphonyl, aminosulphonyl, alkylaminosulphonyl, dialkylaminosulphonyl, alkylcarbonylamino, arylalkylcarbonylamino, arylaminosulphonyl, arylalkylaminosulphonyl, arylcarbonylamino, alkylsulphonylamino, arylsulphonylamino, arylalkylsulphonylamino, alkoxycarbonyl, aryloxycarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, arylalkylaminocarbonyl, pyrrolidino, morpholino, piperazino, N-alkylpiperazino, N-arylpiperazino, N-arylalkyl-piperazino, piperidino, and azabicyclo[3.2.2]nonane; R1 is a hydrogen atom or a straight or branched C1-C4 alkyl group optionally substituted with one or more hydroxy, alkoxy, amino, alkylamino, or dialkylamino groups; R2 and R3, which may be the same or different, are a hydrogen atom, a cycloalkyl group, a straight or branched C1-C6 alkyl group or an aryl group, which are each optionally substituted as described above for R; or R2 and R3, together with the nitrogen atom to which they are bonded, form a 4-morpholinyl, 1-piperazinyl, N-alkyl-piperazinyl, N-aryl-piperazinyl, N-arylalkyl-piperazinyl, piperidinyl, pyrrolidinyl, 2-oxo-1-pyrrolidinyl, imidazolyl or 3-azabicyclo[3.2.2]nonyl ring; R4 is carboxy, a perfluorinated alkyl group, a C2-C4 alkynyl group, 2-oxo-pyrrolidinyl, piperidinyl or a straight or branched C1-C6 alkyl group or an aryl group, which is optionally substituted as described above for R; or a pharmaceutically acceptable salt thereof, and (B) an effective amount of one or more pharmaceutically active agents selected from the group consisting of antibiotic-type agents, alkylating agents, antimetabolite agents, hormonal agents, immunological agents, interferon-type agents, cyclooxygenase inhibitors, metallomatrixprotease inhibitors, telomerase inhibitors, tyrosine kinase inhibitors, anti-growth factor receptor agents, anti-HER agents, anti-EGFR agents, anti-angiogenesis agents, farnesyl transferase inhibitors, ras-raf signal transduction pathway inhibitors, cell cycle inhibitors, cdks inhibitors, tubulin binding agents, topoisomerase I inhibitors, topoisomerase II inhibitors, and chemotherapeutic agents.