6,6-fused heterocyclic compounds as mettl3 inhibitors

A compound of Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• X1 is CR1a or N;
• R1a is selected from the group consisting of H, C1-6alkyl, halo, cycloalkyl, and heteroaryl;
• wherein the C1-6alkyl of R1a is unsubstituted or substituted with aryl;
• X2 is CH or N;
• R1b1 is selected from the group consisting of H, C1-6alkyl, alkenyl, alkynyl, halo, —OR1e, —N(R1e)2, aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclyl;
• wherein the aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclyl of R1b1 is unsubstituted or substituted with one or more substituents selected from the group consisting of C1-6alkyl, halo, —CN, —(CH2)mNH2, —(CH2)mOH, —C(O)R1e, —C(O)N(R1e)2, —(CH2)mCOOH, aryl, —(CH2)maryl, cycloalkyl, oxo, —OR1e, —N(R1e)2, —S(O)2R1e, —S(O)2N(R1e)2, —NHS(O)2R1e, —(CH2)mNH(CH2)mS(O)2R1e, and —NHC(O)R1e;
• wherein the C1-6alkyl and alkynyl of R1b1 is unsubstituted or substituted with one or more substituents selected from the group consisting of aryl, heterocyclyl, and cycloalkyl;
• R1c1 is selected from the group consisting of H, C1-6alkyl, halo, —CN, —N(R1d)2, and —OR1d;
• wherein R1d is H, C1-6alkyl, —(CH2)mCN, —(CH2)mNH2, cycloalkyl, or heterocyclyl;
• wherein each R1e is independently H, C1-6alkyl, —(CH2)mCN, —(CH2)mNH2, cycloalkyl, or heterocyclyl;
• wherein each m is independently 1, 2, or 3;
• Z is
• X20 is CR20a or N;
• wherein R20a is H, halo, CN, aryl, or heteroaryl;
• X21 is CH or N;
• X22 is CR22a or N;
• wherein R22a is H, halo, CN, aryl, or heteroaryl;
• X23 is CH2, S, O, NH;
• X24 and X25 are independently C or N;
• X26 and X27 are independently CH, O, S, N, or NR26a;
• wherein R26a is H or C1-6alkyl;
• X28 is CH or N;
• X29 is CH or N;
• B2, B3, and B4 are independently selected from the group consisting of H, C1-6alkyl, CN, —CH2—NR2aR2b,
• R2a is H or C1-6alkyl;
• R2b is selected from the group consisting of H, C1-6alkyl, aryl, heteroaryl, heterocyclyl, —C(NH)-aryl, and cycloalkyl;
• wherein the C1-6alkyl, aryl, heteroaryl, heterocyclyl, and cycloalkyl of R2b is unsubstituted or substituted with one or more substituents selected from the group consisting of C1-6alkyl, OH, —N(R2h)2, —C(NH)-aryl, alkoxy, aryl, haloaryl, cycloalkyl, halocycloalkyl, hydroxycycloalkyl, and heterocyclyl;
• or
• R2a and R2b combine to form a 5-7-membered heterocyclyl, wherein the heterocyclyl is unsubstituted or substituted with C1-6alkyl;
• R2c, R2d, R2e, and R2f are each independently H, C1-6alkyl, heterocyclyl, or —NHR2g;
• R2g is selected from the group consisting of H and C1-6alkyl, wherein the C1-6alkyl is unsubstituted or substituted with cycloalkyl;
• each R2h is independently H, C1-6alkyl, —(CH2)nCl, or —(CH2)nOCH3;
• n is 1, 2, 3, 4, 5, or 6;
• B5 and B6 are independently
• R3a, R3b, and R3c are each independently H, halogen, C1-6alkyl, —OR3x, —NR3yR3z, cycloalkyl, or heterocyclyl;
• wherein heterocyclyl is unsubstituted or substituted with one or more substituents selected from the group consisting of C1-6alkyl, halogen, —NR3y′R3z′, and —OR3x′;
• R3x and R3x′ are each independently selected from the group consisting of H and C1-6alkyl;
• R3y, R3z, R3y′, and R3z′ are each independently H, C1-6alkyl, or cycloalkyl;
• wherein C1-6alkyl is unsubstituted or substituted with one or more substituents selected from the group consisting of cycloalkyl and —OCH3;
• R3d is selected from the group consisting of Hand C1-6alkyl;
• wherein C1-6alkyl is unsubstituted or substituted with cycloalkyl;
• and
• R3e is selected from the group consisting of H and C1-6alkyl;
• wherein C1-6alkyl is unsubstituted or substituted with cycloalkyl.

A compound of Formula (II), (III), (IV), (V), or (VI):

• or a pharmaceutically acceptable salt thereof, wherein:
• X3, X5, X7, X9, and X11 are independently CR1a or N;
• R1a is selected from the group consisting of H, C1-6alkyl, halo, cycloalkyl, and heteroaryl;
• wherein the C1-6alkyl of R1a is unsubstituted or substituted with aryl;
• X4, X6, X8, X10, and X12 are independently CH or N;
• R1b2, R1b3, R1b4, R1b5, and R1b6 are independently selected from the group consisting of H, C1-6alkyl, alkenyl, alkynyl, halo, —OR1e, —N(R1e)2, aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclyl;
• wherein the aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclyl of R1b2, R1b3, R1b4, R1b5, and R1b6 is unsubstituted or substituted with one or more substituents selected from the group consisting of C1-6alkyl, halo, —CN, —(CH2)mNH2, —(CH2)mOH, —C(O)R1e, —C(O)N(R1e)2, —(CH2)mCOOH, aryl, —(CH2)maryl, cycloalkyl, oxo, —OR1e, —N(R1e)2, —S(O)2R1e, —S(O)2N(R1e)2, —NHS(O)2R1e, —(CH2)mNH(CH2)mS(O)2R1e, and —NHC(O)R1e;
• wherein the C1-6alkyl and alkynyl of R1b2, R1b3, R1b4, R1b5, and R1b6 is unsubstituted or substituted with one or more substituents selected from the group consisting of aryl, heterocyclyl, and cycloalkyl;
• R1c2, R1c3, and R1c4 are independently selected from the group consisting of H, C1-6alkyl, halo, —CN, —N(R1d)2, and —OR1d;
• wherein R1d is H, C1-6alkyl, —(CH2)mCN, —(CH2)mNH2, cycloalkyl, or heterocyclyl;
• wherein each R1e is independently H, C1-6alkyl, —(CH2)mCN, —(CH2)mNH2, cycloalkyl, or heterocyclyl;
• wherein each m is independently 1, 2, or 3;
• X20 is CR20a or N;
• wherein R20a is H, halo, CN, aryl, or heteroaryl;
• X21 is CH or N;
• X22 is CR22a or N;
• wherein R22a is H, halo, aryl, or heteroaryl;
• X23 is CH, S, O, or NH;
• X24 and X25 are independently C or N;
• X26 and X27 are independently CH, O, S, N, or NR26a;
• wherein R26a is H or C1-6alkyl;
• X28 is CH or N;
• B2, B3, and B4 are independently selected from the group consisting of H, C1-6alkyl, CN, —CH2—NR2aR2b,
• R2a is H or C1-6alkyl;
• R2b is selected from the group consisting of H, C1-6alkyl, aryl, heteroaryl, heterocyclyl, —C(NH)-aryl, and cycloalkyl;
• wherein the C1-6alkyl, aryl, heteroaryl, heterocyclyl, and cycloalkyl of R2b is unsubstituted or substituted with one or more substituents selected from the group consisting of C1-6alkyl, OH, —N(R2h)2, —C(NH)-aryl, alkoxy, aryl, haloaryl, cycloalkyl, halocycloalkyl, hydroxycycloalkyl, and heterocyclyl;
• or
• R2a and R2b combine to form a 5-7-membered heterocyclyl, wherein the heterocyclyl is unsubstituted or substituted with C1-6alkyl;
• R2c, R2d, R2e, and R2f are each independently H, C1-6alkyl, heterocyclyl, or —NHR2g;
• R2g is selected from the group consisting of H and C1-6alkyl, wherein the C1-6alkyl is unsubstituted or substituted with cycloalkyl;
• each R2h is independently H, C1-6alkyl, —(CH2)nCl, or —(CH2)nOCH3;
• n is 1, 2, 3, 4, 5, or 6;
• X29 is CH or N;
• B5 and B6 are independently
• R3a, R3b, and R3c are each independently H, halogen, C1-6alkyl, —OR3x, —NR3yR3z, cycloalkyl, or heterocyclyl;
• wherein heterocyclyl is unsubstituted or substituted with one or more substituents selected from the group consisting of C1-6alkyl, halogen, —NR3y′R3z′, and —OR3x′;
• R3x and R3x′ are each independently selected from the group consisting of H and C1-6alkyl;
• R3y, R3z, R3y′, and R3z′ are each independently H, C1-6alkyl, or cycloalkyl;
• wherein C1-6alkyl is unsubstituted or substituted with one or more substituents selected from the group consisting of cycloalkyl and —OCH3;
• R3d is selected from the group consisting of H and C1-6alkyl;
• wherein C1-6alkyl is unsubstituted or substituted cycloalkyl;
• and
• R3e is selected from the group consisting of H and C1-6alkyl;
• wherein C1-6alkyl is unsubstituted or substituted cycloalkyl.

A compound of Formula (II):

• or a pharmaceutically acceptable salt thereof, wherein:
• X3 is CR1a or N;
• R1a is selected from the group consisting of H, C1-6alkyl, halo, cycloalkyl, and heteroaryl;
• wherein the C1-6alkyl of R1a is unsubstituted or substituted with aryl;
• X4 is CH or N;
• R1b2 is selected from the group consisting of H, C1-6alkyl, alkenyl, alkynyl, halo, —OR1e, —N(R1e)2, aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclyl;
• wherein the aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclyl of R1b2 is unsubstituted or substituted with one or more substituents selected from the group consisting of C1-6alkyl, halo, —CN, —(CH2)mNH2, —(CH2)mOH, —C(O)R1e, —C(O)N(R1e)2, —(CH2)mCOOH, aryl, —(CH2)maryl, cycloalkyl, oxo, —OR1e, —N(R1e)2, —S(O)2R1e, —S(O)2N(R1e)2, —NHS(O)2R1e, —(CH2)mNH(CH2)mS(O)2R1e, and —NHC(O)R1e;
• wherein the C1-6alkyl and alkynyl of R1b2 is unsubstituted or substituted with one or more substituents selected from the group consisting of aryl, heterocyclyl, and cycloalkyl;
• R1c2 is selected from the group consisting of H, C1-6alkyl, halo, —CN, —N(R1d)2, and —OR1d;
• wherein R1d is H, C1-6alkyl, —(CH2)mCN, —(CH2)mNH2, cycloalkyl, or heterocyclyl;
• wherein each R1e is independently H, C1-6alkyl, —(CH2)mCN, —(CH2)mNH2, cycloalkyl, or heterocyclyl;
• wherein each m is independently 1, 2, or 3;
• X20 is CR20a or N;
• wherein R20a is H, halo, CN, aryl, or heteroaryl;
• X21 is CH or N;
• B2 is selected from the group consisting of H, C1-6alkyl, CN, —CH2—NR2aR2b,
• R2a is H or C1-6alkyl;
• R2b is selected from the group consisting of H, C1-6alkyl, aryl, heteroaryl, heterocyclyl, —C(NH)-aryl, and cycloalkyl;
• wherein the C1-6alkyl, aryl, heteroaryl, heterocyclyl, and cycloalkyl of R2b is unsubstituted or substituted with one or more substituents selected from the group consisting of C1-6alkyl, OH, —N(R2h)2, —C(NH)-aryl, alkoxy, aryl, haloaryl, cycloalkyl, halocycloalkyl, hydroxycycloalkyl, and heterocyclyl;
• or
• R2a and R2b combine to form a 5-7-membered heterocyclyl, wherein the heterocyclyl is unsubstituted or substituted with C1-6alkyl;
• R2c, R2d, R2e, and R2f are each independently H, C1-6alkyl, heterocyclyl, or —NHR2g;
• R2g is selected from the group consisting of H and C1-6alkyl, wherein the C1-6alkyl is unsubstituted or substituted with cycloalkyl;
• each R2h is independently H, C1-6alkyl, —(CH2)nCl, or —(CH2)nOCH3;
• n is 1, 2, 3, 4, 5, or 6.

A compound of Formula (III):

• or a pharmaceutically acceptable salt thereof, wherein:
• X5 is CR1a or N;
• R1a is selected from the group consisting of H, C1-6alkyl, halo, cycloalkyl, and heteroaryl;
• wherein the C1-6alkyl of R1a is unsubstituted or substituted with aryl;
• X6 is CH or N;
• R1b3 is selected from the group consisting of H, C1-6alkyl, alkenyl, alkynyl, halo, —OR1e, —N(R1e)2, aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclyl;
• wherein the aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclyl of R1b3 is unsubstituted or substituted with one or more substituents selected from the group consisting of C1-6alkyl, halo, —CN, —(CH2)mNH2, —(CH2)mOH, —C(O)R1e, —C(O)N(R1e)2, —(CH2)mCOOH, aryl, —(CH2)maryl, cycloalkyl, oxo, —OR1e, —N(R1e)2, —S(O)2R1e, —S(O)2N(R1e)2, —NHS(O)2R1e, —(CH2)mNH(CH2)mS(O)2R1e, and —NHC(O)R1e;
• wherein the C1-6alkyl and alkynyl of R1b3 is unsubstituted or substituted with one or more substituents selected from the group consisting of aryl, heterocyclyl, and cycloalkyl;
• R1c3 is selected from the group consisting of H, C1-6alkyl, halo, —CN, —N(R1d)2, and —OR1d;
• wherein R1d is H, C1-6alkyl, —(CH2)mCN, —(CH2)mNH2, cycloalkyl, or heterocyclyl;
• wherein each R1e is independently H, C1-6alkyl, —(CH2)mCN, —(CH2)mNH2, cycloalkyl, or heterocyclyl;
• wherein each m is independently 1, 2, or 3;
• X22 is CR22a or N;
• wherein R22a is H, halo, aryl, or heteroaryl;
• X23 is CH, S, O, or NH;
• B3 is selected from the group consisting of H, C1-6alkyl, CN, —CH2—NR2aR2b,
• R2a is H or C1-6alkyl;
• R2b is selected from the group consisting of H, C1-6alkyl, aryl, heteroaryl, heterocyclyl, —C(NH)-aryl, and cycloalkyl;
• wherein the C1-6alkyl, aryl, heteroaryl, heterocyclyl, and cycloalkyl of R2b is unsubstituted or substituted with one or more substituents selected from the group consisting of C1-6alkyl, OH, —N(R2h)2, —C(NH)-aryl, alkoxy, aryl, haloaryl, cycloalkyl, halocycloalkyl, hydroxycycloalkyl, and heterocyclyl;
• or
• R2a and R2b combine to form a 5-7-membered heterocyclyl, wherein the heterocyclyl is unsubstituted or substituted with C1-6alkyl;
• R2c, R2d, R2e, and R2f are each independently H, C1-6alkyl, heterocyclyl, or —NHR2g;
• R2g is selected from the group consisting of H and C1-6alkyl, wherein the C1-6alkyl is unsubstituted or substituted with cycloalkyl;
• each R2h is independently H, C1-6alkyl, —(CH2)nCl, or —(CH2)nOCH3;
• n is 1, 2, 3, 4, 5, or 6.

A compound of Formula (IV):

• or a pharmaceutical y acceptable salt thereof, wherein:
• X7 is CR1a or N;
• R1a is selected from the group consisting of H, C1-6alkyl, halo, cycloalkyl, and heteroaryl;
• wherein the C1-6alkyl of R1a is unsubstituted or substituted with aryl;
• X8 is CH or N;
• R1b4 is selected from the group consisting of H, C1-6alkyl, alkenyl, alkynyl, halo, —OR1e, —N(R1e)2, aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclyl;
• wherein the aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclyl of R1b4 is unsubstituted or substituted with one or more substituents selected from the group consisting of C1-6alkyl, halo, —CN, —(CH2)mNH2, —(CH2)mOH, —C(O)R1e, —C(O)N(R1e)2, —(CH2)mCOOH, aryl, —(CH2)maryl, cycloalkyl, oxo, —OR1e, —N(R1e)2, —S(O)2R1e, —S(O)2N(R1e)2, —NHS(O)2R1e, —(CH2)mNH(CH2)mS(O)2R1e, and —NHC(O)R1e;
• wherein the C1-6alkyl and alkynyl of R1b4 is unsubstituted or substituted with one or more substituents selected from the group consisting of aryl, heterocyclyl, and cycloalkyl;
• R1c4 is selected from the group consisting of H, C1-6alkyl, halo, —CN, —N(R1d)2, and —OR1d;
• wherein R1d is H, C1-6alkyl, —(CH2)mCN, —(CH2)mNH2, cycloalkyl, or heterocyclyl;
• wherein each R1e is independently H, C1-6alkyl, —(CH2)mCN, —(CH2)mNH2, cycloalkyl, or heterocyclyl;
• wherein each m is independently 1, 2, or 3;
• X24 and X25 are independently C or N;
• X26 and X27 are independently CH, O, S, N, or NR26a;
• wherein R26a is H or C1-6alkyl;
• X28 is CH or N;
• B4 is selected from the group consisting of H, C1-6alkyl, CN, —CH2—NR2aR2b,
• R2a is H or C1-6alkyl;
• R2b is selected from the group consisting of H, C1-6alkyl, aryl, heteroaryl, heterocyclyl, —C(NH)-aryl, and cycloalkyl;
• wherein the C1-6alkyl, aryl, heteroaryl, heterocyclyl, and cycloalkyl of R2b is unsubstituted or substituted with one or more substituents selected from the group consisting of C1-6alkyl, OH, —N(R2h)2, —C(NH)-aryl, alkoxy, aryl, haloaryl, cycloalkyl, halocycloalkyl, hydroxycycloalkyl, and heterocyclyl;
• or
• R2a and R2b combine to form a 5-7-membered heterocyclyl, wherein the heterocyclyl is unsubstituted or substituted with C1-6alkyl;
• R2c, R2d, R2e, and R2f are each independently H, C1-6alkyl, heterocyclyl, or —NHR2g;
• R2g is selected from the group consisting of H and C1-6alkyl, wherein the C1-6alkyl is unsubstituted or substituted with cycloalkyl;
• each R2h is independently H, C1-6alkyl, —(CH2)nCl, or —(CH2)nOCH3;
• n is 1, 2, 3, 4, 5, or 6.

A compound of Formula (V):

• or a pharmaceutically acceptable salt thereof, wherein:
• X9 is CR1a or N;
• R1a is selected from the group consisting of H, C1-6alkyl, halo, cycloalkyl, and heteroaryl;
• wherein the C1-6alkyl of R1a is unsubstituted or substituted with aryl;
• X10 is CH or N;
• R1bs is selected from the group consisting of H, C1-6alkyl, alkenyl, alkynyl, halo, —OR1e, —N(R1e)2, aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclyl;
• wherein the aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclyl of R1b5 is unsubstituted or substituted with one or more substituents selected from the group consisting of C1-6alkyl, halo, —CN, —(CH2)mNH2, —(CH2)mOH, —C(O)R1e, —C(O)N(R1e)2, —(CH2)mCOOH, aryl, —(CH2)maryl, cycloalkyl, oxo, —OR1e, —N(R1e)2, —S(O)2R1e, —S(O)2N(R1e)2, —NHS(O)2R1e, —(CH2)mNH(CH2)mS(O)2R1e, and —NHC(O)R1e;
• wherein the C1-6alkyl and alkynyl of R1bs is unsubstituted or substituted with one or more substituents selected from the group consisting of aryl, heterocyclyl, and cycloalkyl;
• R1e is selected from the group consisting of H, C1-6alkyl, halo, —CN, —N(R1d)2, and —OR1d;
• wherein R1d is H, C1-6alkyl, —(CH2)mCN, —(CH2)mNH2, cycloalkyl, or heterocyclyl;
• wherein each R1e is independently H, C1-6alkyl, —(CH2)mCN, —(CH2)mNH2, cycloalkyl, or heterocyclyl;
• wherein each m is independently 1, 2, or 3;
• X29 is CH or N;
• B5 is
• R3a, R3b, and R3c are each independently H, halogen, C1-6alkyl, —OR3x, —NR3yR3z, cycloalkyl, or heterocyclyl;
• wherein heterocyclyl is unsubstituted or substituted with one or more substituents selected from the group consisting of C1-6alkyl, halogen, —NR3y′R3z′, and —OR3x′;
• R3x and R3x′ are each independently selected from the group consisting of H and C1-6alkyl;
• R3y, R3z, R3y′, and R3z′ are each independently H, C1-6alkyl, or cycloalkyl;
• wherein C1-6alkyl is unsubstituted or substituted with one or more substituents selected from the group consisting of cycloalkyl and —OCH3;
• R3d is selected from the group consisting of H and C1-6alkyl;
• wherein C1-6alkyl is unsubstituted or substituted with cycloalkyl;
• and
• R3e is selected from the group consisting of H and C1-6alkyl;
• wherein C1-6alkyl is unsubstituted or substituted with cycloalkyl.

A compound of Formula (VI):

• or a pharmaceutically acceptable salt thereof, wherein:
• X11 is CR1a or N;
• R1a is selected from the group consisting of H, C1-6alkyl, halo, cycloalkyl, and heteroaryl;
• wherein the C1-6alkyl of R1a is unsubstituted or substituted with aryl;
• X12 is CH or N;
• R1b6 is selected from the group consisting of H, C1-6alkyl, alkenyl, alkynyl, halo, —OR1e, —N(R1e)2, aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclyl;
• wherein the aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclyl of R1b6 is unsubstituted or substituted with one or more substituents selected from the group consisting of C1-6alkyl, halo, —CN, —(CH2)mNH2, —(CH2)mOH, —C(O)R1e, —C(O)N(R1e)2, —(CH2)mCOOH, aryl, —(CH2)maryl, cycloalkyl, oxo, —OR1e, —N(R1e)2, —S(O)2R1e, —S(O)2N(R1e)2, —NHS(O)2R1e, —(CH2)mNH(CH2)mS(O)2R1e, and —NHC(O)R1e;
• wherein the C1-6alkyl and alkynyl of R1b6 is unsubstituted or substituted with one or more substituents selected from the group consisting of aryl, heterocyclyl, and cycloalkyl;
• R1c6 is selected from the group consisting of H, C1-6alkyl, halo, —CN, —N(R1d)2, and —OR1d;
• wherein R1d is H, C1-6alkyl, —(CH2)mCN, —(CH2)mNH2, cycloalkyl, or heterocyclyl;
• wherein each R1e is independently H, C1-6alkyl, —(CH2)mCN, —(CH2)mNH2, cycloalkyl, or heterocyclyl;
• wherein each m is independently 1, 2, or 3;
• B6 is
• R3a, R3b, and R3c are each independently H, halogen, C1-6alkyl, —OR3x, —NR3yR3z, cycloalkyl, or heterocyclyl;
• wherein heterocyclyl is unsubstituted or substituted with one or more substituents selected from the group consisting of C1-6alkyl, halogen, —NR3y′R3z′, and —OR3x′;
• R3x and R3x′ are each independently selected from the group consisting of H and C1-6alkyl;
• R3y, R3z, R3y′, and R3z′ are each independently H, C1-6alkyl, or cycloalkyl;
• wherein C1-6alkyl is unsubstituted or substituted with one or more substituents selected from the group consisting of cycloalkyl and —OCH3;
• R3d is selected from the group consisting of Hand C1-6alkyl;
• wherein C1-6alkyl is unsubstituted or substituted with cycloalkyl;
• and
• R3e is selected from the group consisting of H and C1-6alkyl;
• wherein C1-6alkyl is unsubstituted or substituted with cycloalkyl.

A compound of Formula (VII), or a pharmaceutically acceptable salt thereof, having the structure:

• wherein:
• R1b2 is selected from the group consisting of H, C1-6alkyl, alkenyl, alkynyl, halo, —OR1e, —N(R1e)2, aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclyl;
• wherein the aryl, cycloalkyl, cycloalkenyl, heteroaryl, and heterocyclyl of R1b2 is unsubstituted or substituted with one or more substituents selected from the group consisting of C1-6alkyl, halo, —CN, —(CH2)mN(R1e)2, —(CH2)mOH, —C(O)R1e, —C(O)N(R1e)2, —(CH2)mCOOH, aryl, heteroaryl, heterocyclyl, —(CH2)maryl, cycloalkyl, oxo, —OR1e, —N(R1e)2, —S(O)2R1e, —S(O)2N(R1e)2, —NHS(O)2R1e, —(CH2)mNH(CH2)mS(O)2R1e, and —NHC(O)R1e;
• wherein the C1-6alkyl and alkynyl of R1b2 is unsubstituted or substituted with one or more substituents selected from the group consisting of aryl, heteroaryl, heterocyclyl, and cycloalkyl;
• wherein each R1e is independently H, C1-6alkyl, —(CH2)mCN, —(CH2)mNH2, cycloalkyl, or heterocyclyl;
• wherein each m is independently 1, 2, or 3;
• R2a is H or C1-6alkyl;
• wherein the C1-6alkyl of Ra is unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, —OH, —CN, —N(R2h)2, alkoxy, cycloalkyl, halocycloalkyl, hydroxycycloalkyl, and heterocyclyl;
• R2b is selected from the group consisting of C1-6alkyl, heterocyclyl, cycloalkyl, heterocyclylalkyl, and cycloalkylalkyl;
• wherein the C1-6alkyl, heterocyclyl, cycloalkyl, heterocyclylalkyl, and cycloalkylalkyl of R2b is unsubstituted or substituted with one or more substituents selected from the group consisting of C1-6alkyl, C1-6haloalkyl, halogen, —OH, —CN, —N(R2h)2, alkoxy, aryl, haloaryl, cycloalkyl, halocycloalkyl, hydroxycycloalkyl, and heterocyclyl;
• or Ra and R2b combine to form a 5-8-membered heterocyclyl;
• each R2h is independently H, C1-6alkyl, or —(CH2)nOCH3;
• and
• n is 1, 2, 3, 4, 5, or 6.

A compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

• 5-{6,6-difluoro-2-azaspiro[3.3]heptan-2-yl}-2-({6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridin-2-yl}methyl)-1,2-dihydro-2,7-naphthyridin-1-one;
• 5-(4,4-difluoropiperidin-1-yl)-2-({6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridin-2-yl}methyl)-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-({6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5-(morpholin-4-yl)-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-({6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5-{7-oxa-2-azaspiro[3.5]nonan-2-yl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 5-((1 S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-2-((6-((4,4-dimethylpiperidin-1-yl)methyl)imidazo[1,2-a]pyridin-2-yl)methyl)-2,7-naphthyridin-1(2H)-one;
• 2-({6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5-[(1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-({6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5-{hexahydro-1H-furo[3,4-c]pyrrol-5-yl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-({6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5-[3-(morpholin-4-yl)azetidin-1-yl]-1,2-dihydro-2,7-naphthyridin-1-one;
• 5-{2,7-diazaspiro[3.5]nonan-2-yl}-2-({6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridin-2-yl}methyl)-1,2-dihydro-2,7-naphthyridin-1-one;
• 5-(3,4-dihydro-2H-1,4-benzoxazin-4-yl)-2-({6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridin-2-yl}methyl)-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-({6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5-phenyl-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-({6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5-(quinolin-5-yl)-1,2-dihydro-2,7-naphthyridin-1-one;
• 4-[7-({6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridin-2-yl}methyl)-8-oxo-7,8-dihydro-2,7-naphthyridin-4-yl]benzene-1-sulfonamide;
• 2-((6-((4,4-dimethylpiperidin-1-yl)methyl)imidazo[1,2-a]pyridin-2-yl)methyl)-5-(pyridin-4-ylethynyl)-2,7-naphthyridin-1(2H)-one;
• 5-{3-[(dimethylamino)methyl]azetidin-1-yl}-2-({6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridin-2-yl}methyl)-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-({6-[(4,4-dimethylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5-[3-(4-methylpiperazin-1-yl)azetidin-1-yl]-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-{[6-({6-azaspiro[2.5]octan-6-yl}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5-{7-oxa-2-azaspiro[3.5]nonan-2-yl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-{[6-({2-azaspiro[3.3]heptan-2-yl}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5-{7-oxa-2-azaspiro[3.5]nonan-2-yl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-((6-((7-azaspiro[3.5]nonan-7-yl)methyl)imidazo[1,2-a]pyridin-2-yl)methyl)-5-(7-oxa-2-azaspiro[3.5]nonan-2-yl)-2,7-naphthyridin-1(2H)-one;
• 5-{7-oxa-2-azaspiro[3.5]nonan-2-yl}-2-{[6-({2-oxa-7-azaspiro[4.4]nonan-7-yl}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 5-{7-oxa-2-azaspiro[3.5]nonan-2-yl}-2-{[6-({6-oxa-3-azabicyclo[3.1.1]heptan-3-yl}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 5-{7-oxa-2-azaspiro[3.5]nonan-2-yl}-2-[(6-{[4-(trifluoromethyl)piperidin-1-yl]methyl}imidazo[1,2-a]pyridin-2-yl)methyl]-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-{[6-({8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5-{7-oxa-2-azaspiro[3.5]nonan-2-yl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 4-methyl-1-({2-[(5-{7-oxa-2-azaspiro[3.5]nonan-2-yl}-1-oxo-1,2-dihydro-2,7-naphthyridin-2-yl)methyl]imidazo[1,2-a]pyridin-6-yl}methyl)piperidine-4-carbonitrile;
• 2-{[6-({6,6-difluoro-2-azaspiro[3.3]heptan-2-yl}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5-{7-oxa-2-azaspiro[3.5]nonan-2-yl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-{[6-({6-fluoro-2-azaspiro[3.3]heptan-2-yl}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5-{7-oxa-2-azaspiro[3.5]nonan-2-yl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-{[6-({2-azaspiro[4.4]nonan-2-yl}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5-{7-oxa-2-azaspiro[3.5]nonan-2-yl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-({6-[(4-methylpiperidin-1-yl)methyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5-{7-oxa-2-azaspiro[3.5]nonan-2-yl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-({6-[(4,4-difluoropiperidin-1-yl)methyl]imidazo[1,2-a]pyridin-2-yl}methyl)-5-{7-oxa-2-azaspiro[3.5]nonan-2-yl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-{[6-({2,2-difluoro-6-azaspiro[3.4]octan-6-yl}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5-{7-oxa-2-azaspiro[3.5]nonan-2-yl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-{[6-({1,1-difluoro-6-azaspiro[2.5]octan-6-yl}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5-{7-oxa-2-azaspiro[3.5]nonan-2-yl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 5-{6,6-difluoro-2-azaspiro[3.3]heptan-2-yl}-2-{[6-({[(3-fluorocyclobutyl)methyl]amino}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-{[6-({[(3-fluorocyclobutyl)methyl]amino}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5-{2-oxa-6-azaspiro[3.3]heptan-6-yl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-{[6-({[(3-fluorocyclobutyl)methyl]amino}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5-{7-oxa-2-azaspiro[3.5]nonan-2-yl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-{[6-({[(3-fluorocyclobutyl)methyl]amino}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5-{6-oxa-2-azaspiro[3.5]nonan-2-yl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 5-{7,7-difluoro-2-azaspiro[3.5]nonan-2-yl}-2-{[6-({[(3-fluorocyclobutyl)methyl]amino}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 5-{2,2-difluoro-6-azaspiro[3.4]octan-6-yl}-2-{[6-({[(3-fluorocyclobutyl)methyl]amino}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-{[6-({[(3-fluorocyclobutyl)methyl]amino}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5-[3-(4-fluoropiperidin-1-yl)azetidin-1-yl]-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-{[6-({[(3-fluorocyclobutyl)methyl]amino}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5-[3-(pyridin-4-yl)azetidin-1-yl]-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-{[6-({[(3-fluorocyclobutyl)methyl]amino}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-5-[3-(4-fluorophenyl)azetidin-1-yl]-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-((6-((((3-fluorobicyclo[1.1.1]pentan-1-yl)methyl)amino)methyl)imidazo[1,2-a]pyridin-2-yl)methyl)-5-(6-oxa-2-azaspiro[3.4]octan-2-yl)-2,7-naphthyridin-1(2H)-one;
• 2-[(6-{[((3-fluorobicyclo[1.1.1]pentan-1-yl)methyl)amino]methyl}imidazo[1,2-a]pyridin-2-yl)methyl]-5-{7-oxa-2-azaspiro[3.5]nonan-2-yl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-[(6-{[((3-fluorobicyclo[1.1.1]pentan-1-yl)methyl)amino]methyl}imidazo[1,2-a]pyridin-2-yl)methyl]-5-{6-oxa-2-azaspiro[3.5]nonan-2-yl}-1,2-dihydro-2,7-naphthyridin-1-one;
• 2-[(6-{[({3-fluorobicyclo[1.1.1]pentan-1-yl}methyl)amino]methyl}imidazo[1,2-a]pyridin-2-yl)methyl]-5-(2-fluorophenyl)-1,2-dihydro-2,7-naphthyridin-1-one;
• 4-{7-[(6-{[({3-fluorobicyclo[1.1.1]pentan-1-yl}methyl)amino]methyl}imidazo[1,2-a]pyridin-2-yl)methyl]-8-oxo-7,8-dihydro-2,7-naphthyridin-4-yl}benzamide;
• 5-cyclobutyl-2-{[6-({[(3-fluorocyclobutyl)methyl]amino}methyl)imidazo[1,2-a]pyridin-2-yl]methyl}-1,2-dihydro-2,7-naphthyridin-1-one;
• and
• 3-[(6-{[({3-fluorobicyclo[1.1.1]pentan-1-yl}methyl)amino]methyl}imidazo[1,2-a]pyridin-2-yl)methyl]-8-{2-oxa-6-azaspiro[3.3]heptan-6-yl}pyrido[3,4-d]pyridazin-4-one.