Pyridine derivatives useful as hcn2 modulators

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

• wherein
• X1 is N or CR1;
• R1 is selected from:
• H, halo, —CN, C1-6 alkyl, C1-6 haloalkyl, —ORB1, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl and C3-6 cycloalkyl-C1-6 alkyl-, and wherein any alkyl, alkenyl, alkynyl or cycloalkyl group in R1 is optionally substituted with 1 to 4 substituents independently selected from halo, C1-4 alkyl, C1-4 haloalkyl and —ORB2;
• R2 is independently at each occurrence selected from:
• halo, C1-6 alkyl and C1-6 haloalkyl;
• X2 is N or CR32;
• X3 is N or CR33;
• R32 and R33 are independently selected from:
• H, halo, —CN, C1-6 alkyl, C1-6 haloalkyl, —NRA3RA3 and —ORB3;
• R3 is independently at each occurrence selected from:
• halo, —CN, C1-6 alkyl, C1-6 haloalkyl, —NRA3RA3 and —ORB3;
• R4, R5 and R6 are each independently selected from:
• H and C1-4 alkyl,
• or R5 and R6 together with the carbon atom to which they are attached form a C3-6 cycloalkyl;
• R7 is selected from:
• H, halo, —CN, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, —C(O)NRA4RA4, —N(RA4)C(O)RB4 and —C(O)RB4 and;
• R8 is independently at each occurrence selected from:
• H, halo, —CN, nitro, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, —OR10, —NR10R11, —S(O)xR10, —C(O)R10, —OC(O)R10, —C(O)OR10A, —C(O)NR10R11, —N(R11)C(O)R10, —N(R11)C(O)NR10R11, —N(R11)C(O)OR10, —N(R11) SO2R10, —SO2NR10R11, C3-6 cycloalkyl, 3 to 7 membered heterocyclyl, phenyl and or 6 membered heteroaryl;
• wherein said alkyl, alkenyl, alkynyl, cycloalkyl, or heterocyclyl group is optionally substituted with from 1 to 4 R12 groups, and said phenyl or heteroaryl group is optionally substituted with from 1 to 4 R13 groups;
• R81 and R82 are each independently selected from:
• H, halo, —CN, C1-4 alkyl, C1-4 haloalkyl, —OH and —ORB8;
• R9 is selected from H, halo, —CN and C1-6 alkyl;
• R10 is independently at each occurrence selected from:
• H, C1-6 alkyl, C1-6 haloalkyl and C3-6 cycloalkyl;
• wherein said alkyl or cycloalkyl group is optionally substituted with from 1 to 4 R14 groups;
• R10A is selected from:
• C1-6 alkyl, C1-6 haloalkyl and C3-6 cycloalkyl;
• wherein said alkyl or cycloalkyl group is optionally substituted with from 1 to 4 R14 groups;
• R11 is independently at each occurrence selected from:
• H and C1-6 alkyl;
• or R10 and R11 together with the nitrogen to which they are attached form a 4 to 7 membered heterocyclyl, wherein said heterocyclyl is optionally substituted with 1 or 2 substituents selected from halo, ═O, C1-4 alkyl, C1-4 haloalkyl and —ORB7;
• R12 and R14 are each independently at each occurrence selected from:
• halo, ═O, —CN, nitro, C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, —ORB5, —NRA5RA5, —S(O)xRB5, —C(O)RB5, —NRA5C(O)RB5, —C(O)NRA5RA5, —NRA5SO2RB5 and —SO2NRA5RA5;
• R13 is independently at each occurrence selected from:
• halo, —CN, nitro, C1-4 alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, —ORB6, —NRA6RA6, —S(O)xRB6, —C(O)RA6, —NRA6C(O)RB6, —C(O)NRA6RA6, —NRA6SO2RB6, —SO2NRA6RA6;
• RB1 is independently at each occurrence selected from:
• H and C1-6 alkyl;
• RB3 are independently at each occurrence selected from:
• H, C1-6 alkyl and C1-6 haloalkyl;
• RB2, RB4, RB5, RB6, RB7 are independently at each occurrence selected from:
• H, C1-4 alkyl and C1-4 haloalkyl;
• RB8 is independently at each occurrence selected from:
• C1-4 alkyl and C1-4 haloalkyl;
• RA3, RA4, RA5 and RA6 are independently at each occurrence selected from H and C1-4 alkyl;
• m is an integer selected from:
• 0, 1, 2 and 3;
• n is an integer selected from:
• 0, 1 or 2;
• and
• x is independently at each occurrence an integer selected from 0, 1, 2 and 3;
• provided that:
• (i) when X1 is N, then X2 is CR32 and X3 is CR33;
• (ii) when X1 is CR1 and R1 is —CN, then X2 is CR32 and X3 is CR33;
• (iii) when X1 is CR1 and R1 is —CF3, then R8 is not —SO2Me;
• and
• (iv) X2 and X3 are not both N.