Biphenylcarboxylic amide derivatives as p38 kinase inhibitors

A compound of formula (I):

• wherein
• R1 is selected from C1-6alkyl substituted by one to three groups independently selected from oxo, cyano and —S(O)pR4, and C3-7cycloalkyl substituted by one to three groups independently selected from oxo, cyano, —S(O)pR4, OH, halogen, C1-6alkoxy, —NR5R6, —CONR5R6, —NCOR5, —COOR5, —SO2NR5R6, —NHSO2 R5 and —NHCONHR5,
• R2 is selected from hydrogen, C1-6alkyl and —(CH2)q—C3-7cycloalkyl, or
• (CH2)mR1 and R2, together with the nitrogen atom to which they are bound, form a four- to six-membered heterocyclic ring optionally containing one or two additional heteroatoms independently selected from oxygen, sulphur and N—R7, wherein the ring is optionally substituted by one or two groups independently selected from oxo, C1-6alkyl, halogen and trifluoromethyl;
• R3 is the group —CO—NH—(CH2)r—R8 or —NH—CO—R9;
• R4 is selected from hydrogen, C1-6alkyl, heterocyclyl optionally substituted by C1-4alkyl, and phenyl wherein the phenyl is optionally substituted by up to two groups independently selected from C1-6alkoxy, C1-6alkyl and halogen;
• R5 is selected from hydrogen, C1-6alkyl and phenyl wherein the phenyl group is optionally substituted by up to two substituents selected from C1-6alkyl and halogen,
• R6 is selected from hydrogen and C1-6alkyl, or
• R5 and R6, together with the nitrogen atom to which they are bound, form a five- to six-membered heterocyclic or heteroaryl ring optionally containing up to one additional heteroatom selected from oxygen, sulfur and nitrogen, wherein the ring is optionally substituted by up to two C1-6alkyl groups;
• R7 is selected from hydrogen and methyl;
• when r is 0 to 2, R8 is selected from hydrogen, C1-6alkyl, C3-7cycloalkyl, CONHR5, phenyl optionally substituted by R10 and/or R11, heteroaryl optionally substituted by R10 and/or R11 and heterocyclyl optionally substituted by R10 and/or R11, and
• when r is 2, R8 is additionally selected from C1-6alkoxy, NHCOR5, NHCONHR5, NR5R6 and OH;
• R9 is selected from hydrogen, C1-6alkyl, C1-6alkoxy, —(CH2)s—C3-7cycloalkyl, trifluoromethyl, —(CH2)tphenyl optionally substituted by R12 and/or R13, —(CH2)theteroaryl optionally substituted by R12 and/or R13, —(CH2)theterocyclyl optionally substituted by R12 and/or R13 and —(CH2)tfused bicyclyl optionally substituted by R12 and/or R13;
• R10 is selected from C1-6alkyl, C1-6alkoxy, —CONR6R14, —NHCOR14, —SO2NHR14, —NHSO2R14, halogen, trifluoromethyl, —X—(CH2)j-phenyl optionally substituted by one or more halogen atoms or C1-6alkyl groups, —X—(CH2)j-heterocyclyl or —X—(CH2)j-heteroaryl wherein the heterocyclyl or heteroaryl group is optionally substituted by one or more substituents selected from C1-6alkyl,
• R11 is selected from C1-6alkyl and halogen, or
• when R10 and R11 are ortho substituents, then together with the carbon atoms to which they are bound, R10 and R11 may form a five- or six-membered saturated or unsaturated ring to give a fused bicyclic ring system, wherein the ring that is formed by R10 and R11 optionally contains one or two heteroatoms selected from oxygen, nitrogen and sulfur;
• R12 is selected from C1-6alkyl, C1-6alkoxy, —(CH2)s—C3-7cycloalkyl, —CONR15R16, —NHCOR16, —SO2NHR15, —NHSO2R16, halogen, —(CH2)kNR17R18, oxy, trifluoromethyl, phenyl optionally substituted by one or more R13 groups and heteroaryl wherein the heteroaryl is optionally substituted by one or more R13 groups,
• R13 is selected from C1-6alkyl, C1-6alkoxy, halogen, trifluoromethyl and —NR17R18, or
• R12 and R13, together with the carbon atoms to which they are bound, form a five- or six-membered saturated or unsaturated ring to give a fused bicyclic ring system, wherein the ring that is formed by R12 and R13 optionally contains one or two heteroatoms selected from oxygen, nitrogen and sulfur;
• R14 is selected from hydrogen and C1-6alkyl;
• R15 is selected from hydrogen, C1-6alkyl and phenyl wherein the phenyl group may be optionally substituted by one or more R13 groups,
• R16 is selected from hydrogen and C1-6alkyl, or
• R15 and R16, together with the nitrogen atom to which they are bound, form a five- to six-membered heterocyclic ring optionally containing one additional heteroatom selected from oxygen, sulfur and N—R7, wherein the ring is optionally substituted by up to two C1-6alkyl groups;
• R17 is selected from hydrogen, C1-6alkyl and —(CH2)s—C3-7cycloalkyl optionally substituted by C1-6alkyl,
• R18 is selected from hydrogen and C1-6alkyl, or
• R17 and R18, together with the nitrogen atom to which they are bound, form a three- to seven-membered heterocyclic ring optionally containing one additional heteroatom selected from oxygen, sulfur and N—R7, wherein the ring may contain up to one double bond and the ring is optionally substituted by one or more R19 groups;
• R19 is selected from C1-6alkyl, oxy, —CH2OC1-6alkyl, trichloromethyl and —N(C1-6alkyl)2;
• X is selected from —O— and a bond;
• U is selected from methyl and halogen;
• W is selected from methyl and chlorine;
• V and Y are each selected independently from hydrogen, methyl and halogen;
• m is selected from 0, 1, 2, 3 and 4 at least one carbon atom of the resulting carbon chain is optionally substituted with one or two groups selected independently from C1-6alkyl, and wherein the C1-6alkyl group is optionally substituted by up to three OH groups;
• n, p, r and j are independently selected from 0, 1 and 2;
• q and k are independently selected from 0, 1, 2 and 3;
• and
• s and t are independently selected from 0 and 1;
• or a pharmaceutically acceptable derivative thereof.