Heterocyclic compounds as triggering receptor expressed on myeloid cells 2 agonists

A compound of Formula I

• or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein
• R1 is an optionally substituted C1-6 aliphatic group, —OR, —CN, —NR2, —C(═O)R, —C(═O)OR, —C(═O)NR2, —SO2R, —SO2NR2, C1-6haloalkyl, optionally substituted OCH2—(C3-6cycloalkyl), or a cyclic group selected from a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 5-12 membered saturated or partially unsaturated bridged carbocyclic ring, a 7-12 membered saturated or partially unsaturated bicyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring (having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 6-12 membered saturated or partially unsaturated bridged heterocyclic ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 5-6 membered monocyclic heteroaromatic ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and an 8-10 membered bicyclic heteroaromatic ring (having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur), wherein the cyclic group is optionally substituted;
• X1 is CH, CR16, or N;
• Ring A together with the 6-membered ring system to which it is fused forms a bicyclic ring system of formula
• R2 and R3 are each independently selected from hydrogen, an optionally substituted C1-6 aliphatic group, halogen, —OR, —CN, —NR2, —C(═O)R, —C(═O)OR, —C(═O)NR2, —SO2R, —SO2NR2, C1-6haloalkyl, C1-6haloalkoxy, or a cyclic group selected from a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 7-12 membered saturated or partially unsaturated bicyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring (having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 5-6 membered monocyclic heteroaromatic ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and an 8-10 membered bicyclic heteroaromatic ring (having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur), wherein the cyclic group is optionally substituted;
• provided that at least one of R2 and R3 is not hydrogen;
• or R2 and R3 are taken together with their intervening atoms to form a cyclic group selected from a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 7-12 membered saturated or partially unsaturated bicyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring (having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 5-6 membered monocyclic heteroaromatic ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and an 8-10 membered bicyclic heteroaromatic ring (having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur), wherein the cyclic group is optionally substituted;
• X2 is CH, CR14, or N;
• X3 is CH, CR15, or N;
• R4 is selected from hydrogen, an optionally substituted C1-6 aliphatic group, halogen, —OR, —CN, —NR2, —C(═O)R, —C(═O)OR, —C(═O)NR2, —SO2R, —SO2NR2, C1-6haloalkyl, C1-6haloalkoxy, or a cyclic group selected from a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 7-12 membered saturated or partially unsaturated bicyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring (having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 5-6 membered monocyclic heteroaromatic ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and an 8-10 membered bicyclic heteroaromatic ring (having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur), wherein the cyclic group is optionally substituted;
• X4 is NR, O or S;
• Ring B is
• L is a bond or an optionally substituted straight chain or branched C1-6 alkylene;
• X5 is CH, N or CR5;
• X6 is CH, N or CR6;
• provided that when one of X5 or X6 is N, the other is not N;
• R5 and R6 are each independently selected from hydrogen, an optionally substituted C1-6 aliphatic group, —OR, —CN, —NR2, —C(═O)R, —C(═O)OR, —C(═O)NR2, —SO2R, —SO2NR2, halogen, C1-6haloalkyl, C1-6haloalkoxy, or a cyclic group selected from a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 7-12 membered saturated or partially unsaturated bicyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring (having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 5-6 membered monocyclic heteroaromatic ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and an 8-10 membered bicyclic heteroaromatic ring (having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur), wherein the cyclic group is optionally substituted;
• or R5 and R6 are taken together with their intervening atoms to form a cyclic group selected from a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 7-12 membered saturated or partially unsaturated bicyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring (having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 5-6 membered monocyclic heteroaromatic ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and an 8-10 membered bicyclic heteroaromatic ring (having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur), wherein the cyclic group is optionally substituted;
• X7 is N, CH, or CR7;
• X8 is O, NR8, C(R8)2, CHR8, SO2, or C═O;
• X9 is O, NR9, C(R9)2, CHR9, SO2, or C═O;
• X10 is O, NR10, C(R10)2, CHR10, SO2, or C═O;
• X11 is O, NR11, C(R11)2, CHR11, SO2, or C═O;
• X12 is a direct bond, O, NR12, C(R12)2, CHR12, —CH2CH2—, —OCH2—, SO2, or C═O;
• R7 is an optionally substituted aliphatic group, halogen, —OR, —CN, —NR2, —C(═O)R, —C(═O)OR, —C(═O)NR2, —SO2R, —SO2NR2, C1-6haloalkyl, or C1-6haloalkoxy;
• each of R8, R9, R10, R11, and R12 is independently selected from hydrogen, an optionally substituted C1-6 aliphatic group, —OR, —CN, —NR2, —C(═O)R, —C(═O)OR, —C(═O)NR2, —SO2R, —SO2NR2, C1-6haloalkyl, C1-6haloalkoxy, or a cyclic group selected from a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 7-12 membered saturated or partially unsaturated bicyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring (having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 5-6 membered monocyclic heteroaromatic ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and an 8-10 membered bicyclic heteroaromatic ring (having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur), wherein the cyclic group is optionally substituted;
• or any two of R7, R8, R9, R10, R11, and R12 are taken together with their intervening atoms to form a cyclic group selected from a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 7-12 membered saturated or partially unsaturated bicyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring (having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 7-12 membered saturated or partially unsaturated bicyclic heterocyclic ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), a 5-6 membered monocyclic heteroaromatic ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur), and an 8-10 membered bicyclic heteroaromatic ring (having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur), wherein the cyclic group is optionally substituted;
• R13 is an optionally substituted C1-6 aliphatic group, halogen, —OR, —CN, —NR2, —C(═O)R, —C(═O)OR, —C(═O)NR2, —SO2R, —SO2NR2, C1-6haloalkyl, or C1-6haloalkoxy;
• R14 and R15 are each independently an optionally substituted C1-6 aliphatic group, halogen, —OR, —CN, —NR2, —C(═O)R, —C(═O)OR, —C(═O)NR2, —SO2R, —SO2NR2, C1-6haloalkyl, or C1-6haloalkoxy;
• m is 0, 1 or 2;
• R14 and R15 are each independently an optionally substituted C1-6 aliphatic group, halogen, —OR, —CN, —NR2, —C(═O)R, —C(═O)OR, —C(═O)NR2, —SO2R, —SO2NR2, C1-6haloalkyl, or C1-6haloalkoxy;
• R16 is an optionally substituted C1-6 aliphatic group;
• each R is independently hydrogen, or an optionally substituted C1-6 aliphatic group, an optionally substituted phenyl, an optionally substituted 3-7 membered saturated or partially unsaturated carbocyclic ring, an optionally substituted 3-7 membered saturated or partially unsaturated heterocyclic ring (having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur), or an optionally substituted 5-6 membered heteroaryl ring (having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur);
• or
• two R groups on the same nitrogen are taken together with their intervening atoms to form an optionally substituted 4-7 membered saturated, partially unsaturated, or heteroaryl ring (having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, and sulfur).