Substituted 1,6-dihydropyridinones and 1,2-dihydroisoquinolinones as bet inhibitors

A compound of Formula (I):

• or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing,
• wherein:
• Ra is hydrogen, halogen, or C1-C4 alkyl;
• Rb is hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C(O)NR10R11, NR10R11, NR10C(O)R11, NR10S(O)2R11, OR10, S(O)2R10, S(O)2NR10R11, C3-C6 cycloalkyl, or 3- to 6-membered heterocyclyl;
• Re is hydrogen, halogen, cyano, C1-C4 alkyl, or 3- to 6-membered heterocyclyl;
• R1 is hydrogen or C1-C4 alkyl, wherein the C1-C4 alkyl is optionally substituted by 1 or more OH substituents;
• R2 is hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C(O)NR10R11, NR10R11, NR10C(O)R11, NR10S(O)2R11, OC1-C4 alkyl, OC1-C4 haloalkyl, S(O)2R10, S(O)2NR10R11, C3-C6 cycloalkyl, or 3- to 6-membered heterocyclyl;
• R3 is hydrogen, halogen, cyano, C1-C4 alkyl, (CH2)mW3Rg, (CH2)mN(Rf)C(O)ORh, (CH2)mN(Rf)W3Rg, C(O)NR13R14, NR13R14, NR13C(O)R14, NR13C(O)NR13R14, NR13S(O)2R14, NR13S(O)2NR13R14, OR13, S(O)2R1, or S(O)2NR13R14, wherein the C1-C4 alkyl is optionally substituted by 1 or more substituents independently selected from the group consisting of oxo, halogen, cyano, and OH;
• R4 is hydrogen, (CH2)mW3Rg, or (CH2)mN(Rf)W3Rg;
• each W3 is independently —C(O)— or —S(O)2—;
• each Rf is independently hydrogen, C1-C4 alkyl, or C3-C6 cycloalkyl;
• each Rg is independently CRg1=CHRg2 or C≡CRg2;
• each Rg1 is independently hydrogen, cyano, or C1-C4 alkyl, wherein each C1-C4 alkyl is optionally and independently substituted by 1 or more substituents independently selected from the group consisting of NH2, NHCH3, N(CH3)2, OH, and OCH3;
• each Rg2 is independently hydrogen, cyano, or C1-C4 alkyl, wherein each C1-C4 alkyl is optionally and independently substituted by 1 or more substituents independently selected from the group consisting of NH2, NHCH3, N(CH3)2, OH, and OCH3;
• each Rh is independently C1-C6 alkyl or C3-C6 cycloalkyl;
• each R5 is independently hydrogen, halogen, cyano, C1-C4 alkyl, C(O)NR10R11, C(O)OR10, NR10R11, NR10C(O)R11, NR10S(O)2R11, OR10, S(O)2R10, S(O)2NR10R11, C3-C6 cycloalkyl, 3- to 6-membered heterocyclyl, C6-C14 aryl, or 5- to 10-membered heteroaryl, wherein each C1-C4 alkyl, C1-C4 haloalkyl, C(O)NR10R11, C(O)OR10, NR10R11, NR10C(O)R11, NR10S(O)2R11, OR10, S(O)2R10, S(O)2NR10R11, C3-C6 cycloalkyl, 3- to 6-membered heterocyclyl, C6-C14 aryl, and 5- to 10-membered heteroaryl is optionally and independently substituted by 1 or more independently selected R12 substituents;
• W1 is a bond, —NRw1—, or —O—;
• Rw1 is hydrogen, C1-C4 alkyl, or C3-C6 cycloalkyl, wherein the C1-C4 alkyl is optionally substituted by 1 or more substituents independently selected from the group consisting of halogen, oxo, and OH;
• Rc is hydrogen, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C3-C6 cycloalkyl, 3- to 6-membered heterocyclyl, C6-C14 aryl, or 5- or 6-membered heteroaryl, wherein the C3-C6 cycloalkyl, 3- to 6-membered heterocyclyl, C6-C14 aryl, or 5- or 6-membered heteroaryl is optionally substituted by 1 or more independently selected Rc1 substituents;
• each Rc1 is independently oxo, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C(O)NR10R11, NR10R11, NR10C(O)R11, NR10S(O)2R11, OR10, S(O)2R10, S(O)2NR10R11, C3-C6 cycloalkyl, or 3- to 6-membered heterocyclyl;
• W2 is a bond;
• Rd is hydrogen, C1-C4 alkyl, or 3- to 6-membered heterocyclyl;
• each R10 is independently hydrogen, C1-C4 alkyl, C1-C3 alkylene-C3-C6 cycloalkyl, C1-C3 alkylene-3- to 6-membered heterocyclyl, C2-C4 alkenyl, C(O)R12, C3-C6 cycloalkyl, or 3- to 6-membered heterocyclyl, wherein each C1-C4 alkyl is optionally and independently substituted by 1 or more substituents independently selected from the group consisting of oxo, halogen, cyano, C(O)NR13R14, NR13R14, and OH;
• each R11 is independently hydrogen, C1-C4 alkyl, C1-C3 alkylene-C3-C6 cycloalkyl, C1-C3 alkylene-3- to 6-membered heterocyclyl, C2-C4 alkenyl, C(O)R12, C3-C6 cycloalkyl, or 3- to 6-membered heterocyclyl, wherein each C1-C4 alkyl is optionally and independently substituted by 1 or more substituents independently selected from the group consisting of oxo, halogen, cyano, C(O)NR13R14, NR13R14, and OH;
• or
• each R10 and R11, taken together with the atoms to which they are attached, form a 3- to 6-membered heterocyclyl, wherein each 3- to 6-membered heterocyclyl is optionally and independently substituted by 1 or more substituents independently selected from the group consisting of oxo, halogen, cyano, C1-C4 alkyl, and OH, and further wherein each C1-C4 alkyl substituent is optionally and independently substituted by 1 or more substituents independently selected from the group consisting of oxo, halogen, cyano, and OH;
• each R12 is independently halogen, C1-C4 alkyl, C3-C6 cycloalkyl, or 3- to 6-membered heterocyclyl, wherein each C1-C4 alkyl is optionally and independently substituted by 1 or more substituents independently selected from the group consisting of oxo, halogen, cyano, NR 13R14, NR13C(O)R14, and OH;
• each R13 is independently hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, or 3- to 6-membered heterocyclyl, wherein each C1-C4 alkyl is optionally and independently substituted by 1 or more substituents independently selected from the group consisting of oxo, halogen, cyano, and OH;
• each R14 is independently hydrogen, C1-C4 alkyl, C3-C6 cycloalkyl, or 3- to 6-membered heterocyclyl, wherein each C1-C4 alkyl is optionally and independently substituted by 1 or more substituents independently selected from the group consisting of oxo, halogen, cyano, and OH;
• or
• each R13 and R14, taken together with the atoms to which they are attached, form a 3- to 6-membered heterocyclyl, wherein each 3- to 6-membered heterocyclyl is optionally and independently substituted by 1 or more substituents independently selected from the group consisting of oxo, halogen, cyano, C1-C4 alkyl, and OH, and further wherein each C1-C4 alkyl substituent is optionally and independently substituted by 1 or more substituents independently selected from the group consisting of oxo, halogen, cyano, and OH;
• and
• each m is independently 0, 1, 2, 3, or 4;
• with the proviso that at least one of R3 and R4 is (CH2)mW3R9 or (CH2)mN(Rf)W3Rg.