Phenyl- and pyridopyrazole derivatives as inhibitors of DDR1

A compound of formula (I) or a pharmaceutically acceptable salt thereof:

• wherein
• Z1 and Z2 are each selected from —CR8a— and —NR8b—, wherein one of Z1 and Z2 is —CR8a— and the other is —NR8b—;
• and wherein the ring comprising Z1 and Z2 is a pyrazole;
• X1 is independently selected from CR7a and N;
• R1 and R2 are each independently selected at each occurrence from halo, nitro, cyano, NR9R10, OR11, SR9, SO2NR9R9, SO2R9, CO2R9, C(O)R9, CONR9R9, C1-C4-alkyl, C1-C4-alkyl substituted with NR9R10, C1-C4-alkyl substituted with OR11, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl and cyclopropyl;
• R3 is independently selected from H and C1-C4-alkyl;
• R4 is independently selected from C1-C6-alkyl, C1-C6-haloalkyl, C0-C4-alkylene-R4a;
• wherein R4a is independently selected from:
• C3-C8-cycloalkyl, phenyl, 5-, 6-, 9- or 10-membered heteroaryl and 4- to 10-membered heterocycloalkyl;
• wherein said heterocycloalkyl or heteroaryl group may be monocyclic or bicyclic;
• wherein said cycloalkyl or heterocycloalkyl group is optionally substituted with a single R12 group and/or from 1 to 4 R13 groups and wherein said phenyl or heteroaryl group is optionally substituted with a single R12 group and/or from 1 to 3 R14 groups;
• or R3 and R4, together with the nitrogen atom to which they are attached together form a 4- to 10-membered heterocycloalkyl group or a 5-, or 9-membered heteroaryl group;
• wherein said heterocycloalkyl or heteroaryl group may be monocyclic or bicyclic;
• wherein said heterocycloalkyl group is optionally substituted with a single R12 group and/or from 1 to 4 R13 groups and wherein said heteroaryl group is optionally substituted with a single R12 group and/or from 1 to 3 R14 groups;
• R5 is independently at each occurrence selected from H, halo and C1-C4-alkyl, or the two R5 groups and the carbon atom to which they are attached may together form a C3-C6 cycloalkyl ring;
• R6 is independently selected from H, C1-C4-alkyl, C1-C4-haloalkyl and cyclopropyl;
• R7 and R7a are each independently selected from H, halo, nitro, cyano, NR9R10, OR11, SR9, SO2NR9R9, SO2R9, CO2R9, C(O)R9, CONR9R9, C1-C4-alkyl, C1-C4-alkyl substituted with NR9R10, C1-C4-alkyl substituted with OR11, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl and cyclopropyl;
• R8a is independently selected from H, halo, nitro, cyano, NR9R10, OR11, SR9, SO2NR9R9, SO2R9, CO2R9, C(O)R9, CONR9R9, C1-C4-alkyl, C1-C4-alkyl substituted with NR9R10, C1-C4-alkyl substituted with OR11, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl and C0-C4-alkylene-R8c;
• R8b is independently selected from H, C1-C4-alkyl, C2-C4-alkyl substituted with NR9R10, C2-C4-alkyl substituted with OR11, C3-C4-alkenyl, C3-C4-alkynyl, C1-C4-haloalkyl and C0-C4-alkylene-R8c;
• R8c is independently selected from C3-C6-cycloalkyl and 3- to 7-membered heterocycloalkyl;
• wherein said heterocycloalkyl group is attached to the C0-C4-alkylene via a carbon atom in the heterocycloalkyl ring;
• wherein said cycloalkyl or heterocycloalkyl group is optionally substituted with from 1 to 4 R13 groups;
• R9 is independently at each occurrence selected from H and C1-C4-alkyl;
• or two R9 groups, together with the nitrogen atom to which they are attached together form a C5-C8-heterocycloalkyl group optionally substituted with from 0 to 4 R13 groups;
• R10 is independently at each occurrence selected from H, C1-C4-alkyl, C(O)—C1-C4-alkyl and S(O)2—C1-C4-alkyl;
• or R9 and R10, together with the nitrogen atom to which they are attached together form a C5-C8-heterocycloalkyl group optionally substituted with from 0 to 4 R13 groups;
• R11 is independently at each occurrence selected from H, C1-C4-alkyl, C(O)—C1-C4-alkyl and C1-C4-haloalkyl;
• R12 is independently selected from C3-C6-cycloalkyl, phenyl, 5- or 6-membered heteroaryl and 3- to 6-membered-heterocycloalkyl;
• wherein said cycloalkyl or heterocycloalkyl group is optionally substituted with from 1 to 4 R13 groups and wherein said phenyl or heteroaryl group is optionally substituted with from 1 to 3 R14 groups;
• R13 is independently at each occurrence selected from ═O, halo, nitro, cyano, NR8R9, OR14, SR8, SO2NR8R8, CO2R8, C(O)R8, CONR8R8, C1-C4-alkyl, C1-C4-alkyl substituted with OR11, C1-C4-alkyl substituted with NR9R10, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C6-C10-aryl, and C3-C6-cycloalkyl;
• R14 is independently at each occurrence selected from halo, nitro, cyano, NR8R9, OR10, SR8, SO2R8, SO2NR8R8, CO2R8, C(O)R8, CONR8R9, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C1-C4-alkyl substituted with OR11, C1-C4-alkyl substituted with NR8R9 and cyclopropyl;
• m is an integer selected from 0, 1, 2 and 3;
• n is an integer selected from 0, 1 and 2;
• wherein any of the aforementioned alkyl, alkylene or cyclopropyl groups is optionally substituted, where chemically possible, by 1 to 5 substituents which are each independently at each occurrence selected from the group consisting of:
• halo, oxo, fluoro, nitro, cyano, NRaRb, ORa, SRa, CO2Ra, C(O)Ra, CONRaRa, C1-C4-alkyl, C1-C4-haloalkyl and cyclopropyl;
• wherein Ra is independently at each occurrence selected from H, C1-C4-alkyl and C1-C4-haloalkyl;
• and Rb is independently at each occurrence selected from H, C1-C4-alkyl, C(O)—C1-C4-alkyl and S(O)2-C1-C4-alkyl.