Nicotinamide derivatives useful as p38 inhibitors.

A compound of formula (I):

• wherein
• R1 is selected from hydrogen, C1-6alkyl optionally substituted by up to three groups selected from C1-6alkoxy, halogen and hydroxy, C2-6alkenyl, C3-7cycloalkyl optionally substituted by one or more C1-6alkyl groups, phenyl optionally substituted by up to three groups selected from R5 and R6, and heteroaryl optionally substituted by up to three groups selected from R5 and R6,
• R2 is selected from hydrogen, C1-6alkyl and —(CH2)q—C3-7cycloalkyl optionally substituted by one or more C1-6alkyl groups,
• or (CH2)mR1 and R2, together with the nitrogen atom to which they are bound, form a four- to six-membered heterocyclic ring optionally substituted by up to three C1-6alkyl groups;
• R3 is chloro or methyl;
• R4 is the group —NH—CO—R7 or —CO—NH—(CH2)q—R8;
• R5 is selected from C1-6alkyl, C1-6alkoxy, —(CH2)q—C3-7cycloalkyl optionally substituted by one or more C1-6alkyl groups, —CONR9R10, —NHCOR10, —SO2NHR9, —(CH2)SNHSO2R10, halogen, CN, OH, —(CH2)SNR11R12, and trifluoromethyl;
• R6 is selected from C1-6alkyl, C1-6alkoxy, halogen, trifluoromethyl and —(CH2)SNR11R12;
• R7 is selected from hydrogen, C1-6alkyl, —(CH2)q—C3-7cycloalkyl optionally substituted by one or more C1-6alkyl groups, trifluoromethyl, —(CH2)rheteroaryl optionally substituted by R13 and/or R14, and —(CH2)rphenyl optionally substituted by R13 and/or R14;
• R8 is selected from hydrogen, C1-6alkyl, C3-7cycloalkyl optionally substituted by one or more C1-6alkyl groups, CONHR9, phenyl optionally substituted by R13 and/or R14, and heteroaryl optionally substituted by R13 and/or R14;
• R9 and R10 are each independently selected from hydrogen and C1-6alkyl,
• or R9 and R10, 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—R15, wherein the ring may be substituted by up to two C1-6alkyl groups;
• R11 is selected from hydrogen, C1-6alkyl and —(CH2)q—C3-7cycloalkyl optionally substituted by one or more C1-6alkyl groups,
• R12 is selected from hydrogen and C1-6alkyl,
• or R11 and R12, together with the nitrogen atom to which they are bound, form a five or six-membered heterocyclic ring optionally containing one additional heteroatom selected from oxygen, sulfur and N—R15;
• R13 is selected from C1-6alkyl, C1-6alkoxy, —(CH2)q—C3-7cycloalkyl optionally substituted by one or more C1-6alkyl groups, —CONR9R10, —NHCOR10, halogen, CN, —(CH2)SNR11R12, trifluoromethyl, phenyl optionally substituted by one or more R14 groups and heteroaryl optionally substituted by one or more R14 groups;
• R14 is selected from C1-6alkyl, C1-6alkoxy, halogen, trifluoromethyl and —NR11R12;
• R15 is selected from hydrogen and methyl;
• X and Y are each independently selected from hydrogen, methyl and halogen;
• Z is halogen;
• m is selected from 0, 1, 2, 3 and 4, wherein each carbon atom of the resulting carbon chain may be optionally substituted with up to two groups selected independently from C1-6alkyl and halogen;
• n is selected from 0, 1 and 2;
• q is selected from 0, 1 and 2;
• r is selected from 0 and 1;
• and
• s is selected from 0, 1, 2 and 3, or
• a pharmaceutically acceptable salt or solvate thereof.