Bet protein inhibitors and use thereof

A compound according to Formula I:

• or a pharmaceutically acceptable salt thereof,
• wherein:
• R1 is selected from the group consisting of C6-14 aryl and 5- to 10-membered heteroaryl, each of which is optionally substituted with one or more R1a,
• each R1a is independently selected from the group consisting of halogen, —CN, —NO2, —NHRb, —N3, —OH, —SH, —SO3H, C1-8 alkyl, C1-8 alkoxy, C2-8 alkenyl, C2-8 alkynyl, —COORb, —C(O)NHRb, and —C(O)Rc,
• —L1— is selected from the group consisting of —O—, —S—, and —NRa—;
• —L2— is selected from the group consisting of —C(O)— and —SO2—;
• —R2— is selected from the group consisting of phenylene, pyrrol-diyl, furan-diyl, and thiophen-diyl;
• R3 is selected from the group consisting of C3-8 cycloalkyl, 3- to 10-membered heterocyclyl, C6-14 aryl, and 5- to 10-membered heteroaryl, each of which is optionally substituted with one or more R3a,
• each R3a is independently selected from the group consisting of halogen, —CN, —NO2, —NHRb, —N3, —OH, —SH, —SO3H, C1-8 alkyl, C1-8 alkoxy, C2-8 alkenyl, C2-8 alkynyl, —COORb, —C(O)NHRb, and —C(O)Rc;
• alternatively, the grouping —C(O)R3 is an α-aminoacyl moiety;
• subscript n is 1, 2, or 3,
• each Ra and each Rb is independently selected from the group consisting of H and C1-4 alkyl;
• and
• each Rc is independently C1-4 alkyl;
• provided that:
• R3 is substituted with at least one R3a when R1 is unsubstituted phenyl, chlorophenyl, or methoxyphenyl, —L1— is —O—, —L2— is —C(O)—, R2 is phen-1,5-diyl, and R3 is cyclopropyl, tetrahydrofuranyl, or thiophenyl;
• R3 is substituted with at least one R3a when R1 is unsubstituted phenyl or chlorophenyl, —L1— is —O— or —S—, —L2— is —C(O)—, R2 is thiophen-2,4-diyl, and R3 is cyclopropyl or furanyl;
• R1 is substituted with at least one R1a when R1 is phenyl, —L1— is —S—, —L2— is —C(O)—, R2 is phen-2,6-diyl, and R3 is fluorophenyl, tetrahydrofuranyl, or cyclopropyl.

A compound according to Formula II:

• or a pharmaceutically acceptable salt thereof,
• wherein:
• Y is CH or N;
• Z is CH, N, or O;
• R10 is selected from the group consisting of H, C1-8 alkyl, C3-8 cycloalkyl, C2-8 alkenyl, and C2-8 alkynyl, each of which is optionally substituted with one or more R10a;
• each R10a is independently selected from the group consisting of halogen, —CN, —NO2, —NHRe, —N3, —OH, —SH, —SO3H, C1-8 alkyl, C1-8 alkoxy, C2-8 alkenyl, C2-8 alkynyl, —COORe, —C(O)NHRe, and —C(O)Rf;
• R11 is selected from the group consisting of C6-14 aryl, and 5- to 10-membered heteroaryl, each of which is optionally substituted with one or more R11a;
• each R11a is independently selected from the group consisting of halogen, —CN, —NO2, —NHRe, —N3, —OH, —SH, —SO3H, C1-8 alkyl, C1-8 alkoxy, C2-8 alkenyl, C2-8 alkynyl, —COORe, —C(O)NHRe, and —C(O)Rf;
• Rd and each Re is selected from the group consisting of H and C1-4 alkyl;
• and
• each Rf is independently C1-4 alkyl;
• provided that
• R11 is substituted with at least one R11a selected from the group consisting of —CN, —NO2, —NHRe, —N3, —OH, —SH, —SO3H, C1-8 alkoxy, C2-8 alkenyl, C2-8 alkynyl, —COORe, —C(O)NHRe, and —C(O)Rf when R11 is phenyl, Y is CH, Z is N, and R10 is unsubstituted C1-8 alkyl or unsubstituted C3-8 cycloalkyl;
• and
• R11 is substituted with at least one R11a when R11 is furan-2-yl or thiophen-2-yl, Y is CH, Z is N, and R10 is isopropyl, sec-butyl, cyclopentyl, or cyclohexyl.