Patent AU-2010206334-A1 (AU)
Title: Combinations comprising methotrexate and DHODH inhibitors
Inventor: NURIA GODESSART MARINA
IPC: A61P29/00
Filed: 2010-01-19
Abstract: The present invention provides a combination which comprises (a) methotrexate and (b) a non-hepatotoxic DHODH inhibitor of formula (I): wherein: R is selected from the group consisting of hydrogen atoms, halogen atoms, C alkyl, C cycloalkyl, -CF and -OCF, R is selected from the group consisting of hydrogen atoms, halogen atoms and C alkyl groups, R is selected from the group consisting of -COOR, -CONHR, tetrazolyl, -SONHR and -CONHSOR groups, wherein R is selected from the group consisting of a hydrogen atom and linear or branched Calkyl groups, R is selected from the group consisting of a hydrogen atom and a C alkyl group, R is selected from the group consisting of a hydrogen atom and a phenyl group, G represents a group selected from N and CR wherein R is selected from the group consisting of hydrogen atoms, halogen atoms, C alkyl, C cycloalkyl, C alkoxy, -CF, -OCF, monocyclic N-containing C heteroaryl, monocyclic N- containing C heterocyclyl groups and C aryl groups which C aryl groups are optionally substituted with one or more substituents selected from halogen atoms and C alkyl groups, G represents a group selected from N and CR wherein R is selected from the group consisting of hydrogen atoms, halogen atoms, C alkyl, Ccycloalkyl, C alkoxy, -CF, -OCF, monocyclic N-containing C heteroaryl, monocyclic N- containing C heterocyclyl groups and C aryl groups which C aryl groups are optionally substituted with one or more substituents selected from halogen atoms and C alkyl groups, G represents a group selected from: • a hydrogen atom, a hydroxy group, a halogen atom, a C cycloalkyl group, a Calkoxy group and -NRR, wherein R represents a C alkyl group and Rb is selected from a group consisting of C alkyl group and Calkoxy-C alkyl group, or Ra and Rb together with the nitrogen atom to which they are attached form a saturated 6 to 8 membered heterocyclic ring optionally containing one oxygen atom as an additional heteroatom, • a monocyclic or bicyclic 5 to 10 membered heteroaromatic ring containing one or more nitrogen atoms which is optionally substituted by one or more substituents selected from halogen atoms, Calkyl, C alkoxy, C cycloalkyl, C cycloalkoxy, -CF, -OCF, and -CONRR, wherein R and R are independently selected from hydrogen atom, linear or branched C alkyl groups, C cycloalkyl groups, or R and R together with the nitrogen atom to which they are attached form a group of formula wherein n is an integer from 0 to 3, and • a phenyl group which is optionally substituted by one or more substituents selected from halogen atoms, C alkyl, hydroxyl, C alkoxy, Ccycloalkyl, C cycloalkoxy, cyano, -CF, -OCF, -CONRR, oxadiazolyl, triazolyl, pyrazolyl and imidazolyl groups, which oxadiazolyl, triazolyl, pyrazolyl and imidazolyl groups are optionally substituted by C alkyl or C cycloalkyl groups and wherein R and Rare independently selected from hydrogen atom, linear or branched C alkyl groups, C cycloalkyl groups, or R and R together with the nitrogen atom to which they are attached form a group of formula wherein n is an integer from 0 to 3 or, when G' represents CR, Gtogether with R forms a non-aromatic C carbocyclic group or a C aryl group, and the pharmaceutically acceptable salts and N-oxides thereof.