Kinase inhibitors

A compound of Formula I or a pharmaceutically acceptable salt thereof:

• wherein:
• R1 is selected from the group consisting of:
• H, C1-3 alkyl, C1-3 haloalkyl, halo, —OR2, —NR2R2, C3 cycloalkyl and C3 halocycloalkyl;
• each R2 is independently selected from the group consisting of:
• H, C1-3 alkyl and C1-3 haloalkyl;
• each R3 is independently selected from the group consisting of:
• C1-3 alkyl, C1-3 haloalkyl, halo, —OR2, —NR2R2, C3 cycloalkyl and C3 halocycloalkyl;
• n is 1 or 2;
• m is 0 to 3;
• W is
• and X is
• or W is
• and X is
• or W is
• and X is
• or W is
• and X is
• R4 is selected from the group consisting of:
• C3-6 alkyl, C3-6 heteroalkyl, C3-6 haloalkyl, C3-6 heterohaloalkyl, C3-6 alkenyl wherein (i) the carbon atom beta to the ring to which the alkene is bonded is cis-substituted with carbon;
• and (ii) the carbon atom alpha to the ring to which the alkene is bonded substituted with carbon, C3-6 cycloalkyl, C4-6 cycloalkenyl, 4- to 6-membered heterocycloalkyl including 1, 2 or 3 heteroatoms selected from N, O or S, 4- to 6-membered heterocycloalkenyl including 1, 2 or 3 heteroatoms selected from N, O or S, aryl, heteroaryl including 1, 2 or 3 heteroatoms selected from N, O or S, —NRB1aRB2a, —NRB3aC(O)RB2a, —C(O)NRB2aRB2a, —C(O)-(4- to 12-membered non-aromatic saturated or partially saturated monocyclic or fused, bridged, or spiro bicyclic heterocyclic ring system including 1, 2 or 3 heteroatoms selected from N, O or S), —NRB3aC(O)ORB2a, —NRB3aC(O)NRB3aRB3a, —NRB3aSO2RB2a, —SO2NRB3aRB3a, —SO2RB2a and —S(O)(═NRB3a)RB2a;
• R5 is selected from the group consisting of:
• H, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, C1-6 heterohaloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C4-6 cycloalkenyl, 4- to 6-membered heterocycloalkyl including 1, 2 or 3 heteroatoms selected from N, O or S, 4- to 6-membered heterocycloalkenyl including 1, 2 or 3 heteroatoms selected from N, O or S, aryl, heteroaryl including 1, 2 or 3 heteroatoms selected from N, O or S, —O-aryl, —O-heteroaryl, halo, —ORB2a, —NRB3aRB3a, —SRB2a, —CN, —NRB3aC(O)RB2a, —C(O)NRB2aRB2a, —CRB3a(—NRB3a), —NRB3aC(O)ORB2a, —OC(O)NRB3aRB3a, —NRB3aC(O)NRB3aRB3a, —NRB3aC(NRB3a)NRB3aRB3a, —NRB3aSO2RB3a, —SO2NRB3aRB3a, —SO2RB2a, —S(O)(═NRB3a)RB2a and —C(O)ORB2a;
• R6 is selected from the group consisting of:
• H, C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, C1-6 heterohaloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C4-6 cycloalkenyl, 4- to 6-membered heterocycloalkyl including 1, 2 or 3 heteroatoms selected from N, O or S, 4- to 6-membered heterocycloalkenyl including 1, 2 or 3 heteroatoms selected from N, O or S, aryl, heteroaryl including 1, 2 or 3 heteroatoms selected from N, O or S, —O-aryl, —O-heteroaryl, halo, —ORB3a, —NRB3aRB3a, —CRB3a(═NRB3a), —SRB3a, —CN, —NRB3aC(O)RB2a, —C(O)NRB2aRB2a, —NRB3aC(O)ORB2a, —OC(O)NRB3aRB3a, —NRB3aC(O)NRB3aRB3a, —NRB3aC(NRB3a)NRB3aRB3a, —NRB3aSO2RB3a, —SO2NRB3aRB3a, —SO2RB2a, —S(O)(═NRB3a)RB2a and —C(O)ORB2a
• wherein RB1a is selected from the group consisting of:
• C3-4 alkyl, C3-4 heteroalkyl, C3-4 haloalkyl, C3-4 haloheteroalkyl, C3-6 cycloalkyl, C1-4 alkyl C3-6 cycloalkyl, 4- to 12-membered non-aromatic saturated or partially saturated monocyclic or fused, bridged, or spiro bicyclic heterocyclic ring system including 1, 2 or 3 heteroatoms selected from N, O or S;
• wherein RB2a is selected from the group consisting of:
• C1-4 alkyl, C1-4 heteroalkyl, C1-4 haloalkyl, C1-4 haloheteroalkyl, C3-6 cycloalkyl, C1-4 alkyl C3-6 cycloalkyl, 4- to 12-membered non-aromatic saturated or partially saturated monocyclic or fused, bridged, or spiro bicyclic heterocyclic ring system including 1, 2 or 3 heteroatoms selected from N, O or S;
• wherein RB3a is selected from the group consisting of:
• H, C1-4 alkyl, C1-4 heteroalkyl, C1-4 haloalkyl, C1-4 haloheteroalkyl, C3-6 cycloalkyl, C1-4 alkyl C3-6 cycloalkyl, 4- to 12-membered non-aromatic saturated or partially saturated monocyclic or fused, bridged, or spiro bicyclic heterocyclic ring system including 1, 2 or 3 heteroatoms selected from N, O or S;
• wherein the C3-4 alkyl, C3-4 heteroalkyl, C3-4 haloalkyl, C3-4 haloheteroalkyl, C1-4 alkyl, C1-4 heteroalkyl, C1-4 haloalkyl, C1-4 haloheteroalkyl, C3-6 cycloalkyl, C1-4 alkyl C3-6 cycloalkyl and 4- to 12-membered non-aromatic saturated or partially saturated monocyclic or fused, bridged, or spiro bicyclic heterocyclic ring system including 1, 2 or 3 heteroatoms selected from N, O or S can be optionally substituted with C1-4 alkyl, C1-4 heteroalkyl, C1-4 haloalkyl, C1-4 haloheteroalkyl, C3-6 cycloalkyl, C1-4 alkyl C3-6 cycloalkyl, aryl, heteroaryl including 1, 2 or 3 heteroatoms selected from N, O or S, —OH, —O(C1-3 alkyl), —(C1-3 alkyl)-OH, —(C1-3 alkyl)-O(C1-3 alkyl), ═O, —NH2, —NH(C1-3 alkyl), —N(C1-3 alkyl)2 or (C1-3 alkyl)-NH2, —(C1-3 alkyl)-NH(C1-3 alkyl) or —(C1-3 alkyl)-N(C1-3 alkyl)2;
• wherein in the specific groups —NRB1aRB2a, —NRB3aRB3a, —C(O)NRB2aRB2a, —OC(O)NRB3aRB3a, —NRB3aC(O)NRB3aRB3a, —NRB3aC(NRB3a)NRB3aRB3a and —SO2NRB3aRB3a, the pairs RB1a/RB2a, RB3a/RB3a and RB2a/RB2a, together with the nitrogen atom to which they are bonded, can form a 4- to 12-membered monocyclic or fused, bridged, or spiro bicyclic ring system optionally including 1, 2 or 3 heteroatoms selected from N, O or S;
• or wherein R4 is C1-6 alkyl or C3-6 cycloalkyl and R6 is —NRB3aC(O)RB2a, wherein the terminal RB2a is absent and R4 and R6 are joined via the carbonyl carbon, so that, together with the carbon atoms to which they are bonded, R4 and R6 form a 5- or 6-membered ring;
• or wherein R5 is —NRB3aRB3a and R6 is —CRB3a(═NRB3a), wherein the terminal RB3a of —CRB3a(═NRB3a) is absent and one RB3a of —NRB3aRB3a is absent and R5 and R6 are joined via the imine nitrogen atom, so that, together with the carbon atoms to which they are bonded, R5 and R6 form a 5-membered ring;
• provided that, when R4 is aryl or heteroaryl including 1, 2 or 3 heteroatoms selected from N, O or S and R5 is absent or H, one or both of the following is true:
• (i) the aryl or heteroaryl including 1, 2 or 3 heteroatoms selected from N, O or S is ortho-substituted with an Rsub moiety;
• or (ii) R6 is not H;
• wherein each of the aforementioned C3-6 alkyl, C1-6 alkyl, C3-6 heteroalkyl, C3-6 haloalkyl, C1-6 haloalkyl, C3-6 heterohaloalkyl, C1-6 heterohaloalkyl, C3-6 alkenyl, C2-6 alkenyl, C3-6 cycloalkyl, C4-6 cycloalkenyl, 4- to 6-membered heterocycloalkyl including 1, 2 or 3 heteroatoms selected from N, O or S, 4- to 6-membered heterocycloalkenyl including 1, 2 or 3 heteroatoms selected from N, O or S, aryl, heteroaryl, 4- to 12-membered non-aromatic saturated or partially saturated monocyclic or fused, bridged, or spiro bicyclic heterocyclic ring system including 1, 2 or 3 heteroatoms selected from N, O or S and C2-6 alkynyl can be optionally substituted with 1, 2 or 3 Rsub moieties, wherein each Rsub moiety is independently selected from the group consisting of:
• C1-6 alkyl, C1-6 heteroalkyl, C1-6 haloalkyl, C1-6 heterohaloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, 4- to 6-membered heterocycloalkyl including 1, 2 or 3 heteroatoms selected from N, O or S, aryl, heteroaryl including 1, 2 or 3 heteroatoms selected from N, O or S, halo, —ORB3a, ═O, —NRB3aRB3a, —SRB3a, —CN, —NO2, —NRB3aC(O)RB3a, —C(O)NRB3aRB3a, —NRB3aC(O)ORB3a, —OC(O)NRB3aRB3a, —NRB3aC(O)NRB3aRB3a, —NRB3aC(NRB3a)NRB3aRB3a, —NRB3aSO2RB3a, —SO2NRB3aRB3a, —SO2RB3a, —C(O)RB3a and —C(O)ORB3a.