5′-carbamoyl-1,1′-biphenyl-4-carboxamide derivatives and their use as p38 kinase inhibitors

A compound of formula (I):

• wherein
• X is abond;
• R1 is selected from an optionally substituted five- to seven-membered heterocyclic ring, an optionally substituted five- to seven-membered heteroaryl ring and an optionally substituted fused bicyclic ring;
• R2 is selected from hydrogen, C1-6alkyl and —(CH2)p—C3-7cycloalkyl;
• or when X is a bond and m and n are both zero, R1 and R2, 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 and nitrogen, which can be optionally substituted by C1-4alkyl;
• R3is the group —CO—NH—(CH2)q-R4;
• when q is 0 to 2 R4 is selected from hydrogen, C1-6alkyl, —C3-7cycloalkyl, CONHR5, phenyl optionally substituted by R7 and/or R8, heteroaryl optionally substituted by R7 and/or R8 and heterocyclyl optionally substituted by R7 and/or R8;
• and when q is 2 R4 is additionally selected from C1-6alkoxy, NHCOR5, NHCONHR5, NR5R6, and OH;
• R5 is selected from hydrogen, C1-6alkyl and phenyl wherein the phenyl group may be optionally substituted by up to two substituents selected from C1-6alkyl and halogen;
• R6is 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 may be substituted by up to two C1-6alkyl groups;
• R7 is selected from C1-6alkyl, C1-6alkoxy, —CONR6R9, —NHCOR 9, —SO2NHR9, —NHSO2R9, halogen, trifluoromethyl, -Z-(CH2)s—phenyl optionally substituted by one or more halogen atom, -Z-(CH2)s—heterocyclyl or -Z-(CH2)s—heteroaryl wherein the heterocyclyl or heteroaryl group may be optionally substituted by one or more substituents selected from C1-6alkyl;
• R8 is selected C1-6alkyl and halogen;
• or when R7 and R8 are ortho substituents, then together with the carbon atoms to which they are bound, R7 and R8 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 R7 and R8 may optionally contain one or two heteroatoms selected from oxygen, nitrogen and sulfur;
• R9 is selected from hydrogen and C1-6alkyl;
• 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;
• Z is selected from —O—and a bond;
• m and n are independently selected from 0, 1 and 2, wherein each carbon atom of the resulting carbon chain may be optionally substituted with up to two groups selected independently from C1-6alkyl, and the sum of m+n is from 0 to 4;
• p is selected from 0 and 1;
• q and s are selected from 0, 1 and 2;
• r is selected from 0, 1 and 2;
• or a pharmaceutically acceptable salt or solvate thereof.