Heteroaryl compounds for the treatment of pain

A compound of formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• L is —O—, a single bond, —O—C(R)2—, —C(R)2—, —C(R)2—O—, or —N(R)—;
• each R is independently H, halo, or C1-C6 alkyl;
• X2, Y1, Y2, and Y3 are defined as follows:
• (i) X2 is CR2, Y1 is CR1a, Y2 is CR2a, and Y3 is CR3a;
• or
• (ii) X2 is N, Y1 is CR1a, Y2 is CR2a, and Y3 is CR3a;
• or
• (iii) X2 is CR2, Y1 is N, Y2 is CR2a, and Y3 is CR3a;
• or
• (iv) X2 is CR2, Y1 is CR1a, Y2 is N, and Y3 is CR3a;
• or
• (v) X2 is CR2, Y1 is CR1a, Y2 is +N—O−, and Y3 is CR3a;
• or
• (vi) X2 is CR2, Y1 is CR1a, Y2 is CR2a, and Y3 is N;
• X4, X5, X6, and X7 are defined as follows:
• (i) X4 is CR4, X5 is CR5, X6 is CR6, and X7 is CR7;
• or
• (ii) X4 is N, X5 is CR5, X6 is CR6, and X7 is CR7;
• or
• (iii) X4 is CR4, X5 is N, X6 is CR6, and X7 is CR7;
• or
• (iv) X4 is CR4, X5 is CR5, X6 is N, and X7 is CR7;
• or
• (v) X4 is CR4, X5 is CR5, X6 is CR6, and X7 is N;
• or
• (vi) X4 is CR4, X5 is N, X6 is CR6, and X7 is N;
• or
• (vii) X4 is CR4, X5 is N, X6 is N, and X7 is CR7;
• or
• (viii) X4 is CR4, X5 is CR5, X6 is N, and X7 is N;
• R2 is H, halo, C1-C6 alkyl, (C1-C6 alkylene)-NR8R9, C2-C6 alkenyl, C1-C6 alkoxy, (C1-C6 alkylene)-OH, C(O)OR8, or CH(OH)(CH2)m(CHOH)n(CH2)pH;
• R4, R5, R6, and R7 are defined as follows:
• (i) R4, R5, R6, and R7 are each independently H, halo, C1-C6 alkyl, C1-C6 haloalkyl, or C3-C6 cycloalkyl optionally substituted with one or more alkyl, halo, or OH;
• (ii) R4 and R7 are each independently H, halo, C1-C6 alkyl, C1-C6 haloalkyl, or C3-C6 cycloalkyl optionally substituted with one or more halo;
• and
• R5 and R6, together with the carbon atoms to which they are attached, form a ring of formula:
• or
• (iii) R4 and R7 are each independently H, halo, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, or C3-C6 cycloalkyl substituted with one or more halo;
• and
• R5 and R6, together with the carbon atoms to which they are attached, form a ring of formula:
• R8 and R9 are each independently H or C1-C6 alkyl;
• each R10 is independently H or halo;
• R1a is H, halo, CN, C1-C6 alkyl, OH, C(O)NR12R13, C1-C6 alkoxy, NR12R13, NR8C(O)NR8R9, (C1-C6 alkylene)-C(O)NR8R9, (C1-C6 alkylene)-OH, C(O)OR12, OR12, CH(OH)(CH2)m(CHOH)n(CH2)pH, N═S(═O)(CH3)2, N═S(═O)R′R″, 5-10 membered heteroaryl, or 4-10 membered heterocyclyl, wherein the heterocyclyl or heteroaryl in said 5-10 membered heteroaryl or 4-10 membered heterocyclyl is optionally substituted with 1-4 substituents selected from OH, halo, oxo, C(O)NR8R9, NR8R9, C1-C6 alkyl, C1-C6 alkoxy, (C1-C6 alkylene)-OH, (C1-C6 alkylene)-O—(C1C6 alkyl), and (C1-C6 alkylene)-NR8R9;
• R′ and R″, together with the S atom to which they are attached, form a 4-7 membered heterocyclyl;
• R11, R2a, and R3a are each independently H, halo, CN, C1-C6 alkyl, C(O)NR8R9, or C1-C6 alkoxy;
• R12 and R13 are each independently H, C(O)(C1-C6 alkyl), (C1-C6 alkylene)-NR8R9, CH2CH(OH)(CH2)m(CHOH)n(CH2)pH, C1-C6 alkyl optionally substituted with one or more OH, indanyl, (C1-C6 alkylene)-(C3-C6 cycloalkyl), (C1-C6 alkylene)-phenyl, (C1-C6 alkylene)-(5-membered heterocyclyl), C4-C7 cycloalkyl, C6-C10 aryl, 5-6 membered heteroaryl, or 4-7 membered heterocyclyl, wherein the indanyl, (C1-C6 alkylene)-(C3-C6 cycloalkyl), (C1-C6 alkylene)-phenyl, (C1-C6 alkylene)-(5 membered heterocyclyl), C4-C7 cycloalkyl, C6-C10 aryl, 5-6 membered heteroaryl, or 4-7 membered heterocyclyl is optionally substituted with 1-4 substituents selected from OH, oxo, C1-C6 alkyl, (C1-C6 alkylene)-OH, and C1-C6 alkoxy;
• Z1 is, 3-7 membered cycloalkenyl, phenyl, 4-10 membered heterocyclyl, or 5-6 membered heteroaryl, wherein said 3-7 membered cycloalkenyl, phenyl, 4-10 membered heterocyclyl, or 5-6 membered heteroaryl may be unsubstituted or may be substituted with 1-4 substituents selected from halo, OH, CD3, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, CH2OH, C(O)H, and C1-C6 haloalkoxy;
• m, n, and p are each independently 0 or 1;
• and
• q is 1, 2, or 3,
• wherein when X2 is N, then:
• (i) L is O, and Z1 is phenyl, wherein said phenyl is substituted with 2-4 substituents selected from halo, OH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy;
• or
• (ii) L is a single bond, and Z1 is 4-10 membered heterocyclyl, wherein said 4-10 membered heterocyclyl is substituted with 2-4 substituents selected from halo, OH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy;
• and
• wherein when X2, X4, X5, X6 and X7 are each CH, L is a single bond, and Z1 is phenyl, then said phenyl is substituted with 1-4 substituents selected from halo, OH, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and C1-C6 haloalkoxy.