Pyrazolyl-ureas as kinase inhibitors

A method of treatment of a condition selected from exacerbation of COPD and exacerbation of asthma comprising administering to a subject in need thereof an effective amount of a compound of formula (I)

• wherein:
• R1 represents
• Q represents N or CH;
• R2a, R2b and R2c are independently selected from hydrogen, hydroxyl, halogen, —C1-6alkyl, —C1-6haloalkyl, C3-5cycloalkyl;
• —C1-3alkylene-OH, —OC2-3alkylene-OH, —C1-6alkoxy, —C1-3alkylene-N—(C1-3alkyl)2, —N(C1-3alkyl)2, —SC1-3alkyl and —C1-3alkylene-S—C1-3alkyl;
• R2d and R2e are defined as follows:
• either
• (i) R2d represents hydrogen, —C1-8 alkyl in which 1 to 3 carbon atoms are optionally substituted by halogen, —C0-2alkylene-Cyc, —C0-2alkylene-Het, —CH2-J, —C≡C—CH2-J, —NR3R4, —OR5 or —CN;
• and R2e represents hydrogen or —C1-6 alkyl;
• or
• (ii) R2e represents —C0-2alkylene-Cyc, —C0-2alkylene-Het, —CO—K-Cyc, —CO—K′-Het, —CO—K′-HetAr, —CH2-J, —CO-J′, or —C1-8 alkyl in which 1 to 3 carbon atoms are optionally substituted by halogen;
• and R2d represents hydrogen or —C1-6 alkyl;
• or
• (iii) R2d and R2e are joined and together represent a C3-5alkylene chain in which one carbon atom of said alkylene chain, not being in a position adjacent to the pyrazine ring, is optionally replaced by O or NR2f wherein R2f represents H or C1-3alkyl and wherein a carbon atom of said alkylene chain is optionally substituted by one or more groups selected from halogen, oxo and methyl;
• J and J′ independently represent a C1-10 alkyl moiety in which 1, 2 or 3 carbon atoms are replaced by a heteroatom selected from O and N provided that any two heteroatoms if present are separated by at least two carbon atoms and wherein 1 or 2 carbon atoms are optionally substituted by oxo and which moiety is optionally substituted by 1 to 3 halogen groups provided that J′ does not represent OH;
• K and K′ independently represent a bond or a C1-10 alkylene chain in which 1, 2 or 3 carbon atoms are optionally replaced by a heteroatom selected from O and N provided that any two heteroatoms if present are separated by at least two carbon atoms and provided that neither K nor K′ represents O;
• R3 and R4 independently represent H or —C1-8 alkyl optionally substituted by 1 to 3 groups selected from hydroxyl, C1-3alkoxy, hydroxyC1-3alkyl and halogen and wherein 1 or 2 carbon atoms of said alkyl are optionally substituted by oxo;
• or R3 and R4 are joined such that —NR3R4 together represents a 4-7 membered heterocyclic ring optionally substituted by one to three groups selected from C1-3alkyl, hydroxyl, C1-3alkoxy, hydroxyC1-3alkyl and halogen in which a carbon atom separated by at least two carbon atoms from the nitrogen atom is optionally replaced by a heteroatom selected from O and N;
• and wherein a methylene group is optionally substituted by oxo;
• or R3 represents C3-6cycloalkyl and R4 represents hydrogen;
• R5 represents —C1-8 alkyl optionally substituted by 1 to 3 groups selected from hydroxyl, C1-3alkoxy, hydroxyC1-3alkyl and halogen and wherein 1 to 3 carbon atoms are optionally substituted by halogen;
• Het represents a 4 to 7 membered non-aromatic heterocyclic ring containing 1 or 2 heteroatoms selected from O, S and N or an 8 to 10 membered non-aromatic bicyclic heterocyclic ring containing 1, 2 or 3 heteroatoms selected from O, S and N in either case optionally substituted by one to three groups selected from C1-3alkyl, hydroxyl, C1-3alkoxy, hydroxyC1-3alkyl-, C1-3haloalkyl, halogen, oxo, —N(C1-3alkyl)2, —C(═O)C1-3alkyl, —C(═O)OC1-3alkyl, —C1-3 alkylene-N—(C1-3alkyl)2, —C1-3 alkylene-O—C1-3alkyl, C3-6cycloalkyl and a 4-6 membered non-aromatic heterocyclic ring containing 1 or 2 heteroatoms selected from O, S and N optionally substituted by methyl, provided that Het is not directly attached to the pyrazine ring via a heteroatom and wherein a methylene group is optionally substituted by oxo;
• Cyc represents a 3 to 7 membered non-aromatic carbocyclic ring optionally substituted by 1 to 3 groups selected from C1-3alkyl, hydroxyl, C1-3alkoxy, hydroxyC1-3alkyl and halogen and wherein a methylene group is optionally substituted by oxo;
• and
• HetAr represents a 5- or 6 membered heteroaromatic ring containing 1 to 3 heteroatoms selected from O, N and S and optionally substituted by one to three groups selected from C1-3alkyl, hydroxyl, C1-3alkoxy, hydroxyC1-4alkyl-, halogen and C1-3haloalkyl;
• or a pharmaceutically acceptable salt thereof.