Tetrahydroquinoline-based bromodomain inhibitors

A compound having a structure represented by a formula:

• wherein R1 is selected from C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 deuterated alkyl;
• wherein R2 is C1-C4 alkyl;
• wherein R3a is selected from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, Cy2, —(C1-C6 alkyl)Cy2, —(C1-C6 alkyl)Ar4, —C(O)(C1-C6 alkyl), —C(O)(CH2)mCy2, —C(O)(CH2)mAr4, —C(O)(C1-C4 alkyl)CCH, —CO2(C1-C6 alkyl), and amine protecting group, and wherein R3b is selected from —C(O)(unsubstituted C1-C6 alkyl), —C(O)(CH2)mCy2, —C(O)(CH2)mAr4, —C(O)(C1-C4 alkyl)CCH, and -CO2(C1-C6 alkyl);
• wherein m, when present, is selected from 0, 1, 2, and 3;
• wherein Cy2, when present, is selected from C3-C6 cycloalkyl and C3-C6 heterocycloalkyl and is substituted with 0-4 non-hydrogen groups independently selected from halogen, —OH, —CN, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 haloalkyl;
• wherein Ar4, when present, is selected from aryl and heteroaryl and is substituted with 0-4 non-hydrogen groups independently selected from halogen, —OH, —CN, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 haloalkyl;
• or wherein each of R3a and R3b are optionally covalently bonded together and, together with the intermediate atoms, comprise a 5- to 7-membered heteroaryl and are substituted with 0-4 non-hydrogen groups independently selected from halogen, —OH, —CN, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 haloalkyl;
• wherein Ar1 is selected from aryl and is substituted with 0-4 non-hydrogen groups independently selected from halogen, —OH, —CN, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 haloalkyl;
• wherein R4a is selected from hydrogen, C1-C4 alkyl, and amine protecting group and wherein R4b is selected from C4-C8 alkyl, —(CH2)nCy1, —(CH2)oAr2, and —COR6;
• wherein each of n and o, when present, is selected from 0, 1, 2, and 3;
• wherein Cy1, when present, is selected from cycloalkyl, five-membered heterocycle, and six-membered heterocycle and is substituted with 0-4 non-hydrogen groups independently selected from halogen, —OH, —CN, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 haloalkyl;
• wherein Ar2, when present, is selected from aryl and 5- to 12-membered heteroaryl and is substituted with 0-4 non-hydrogen groups independently selected from halogen, —OH, —CN, —NO2, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 aminoalkyl, C3-C6 cycloalkyl, —COR21, —CO2R21, —CONR22aR22b, —(CH2)qNR22aR22b, —SO2NR22aR22b, —NR23C(O)R24, —NR23(CH2)q(C3-C6 cycloalkyl), —NR23(CH2)q(heterocycloalkyl), and 3- to 5-membered heterocycloalkyl;
• wherein q, when present, is selected from 0, 1, 2, 3, and 4;
• wherein each occurrence of R21, when present, is independently selected from hydrogen, C1-C6 alkyl, C1-C6 hydroxyalkyl, C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, —COR30, —(C1-C4 alkyl)OC(O)(C1-C4 alkyl), and —(C1-C6 alkyl)NHC(O)A;
• wherein A has a structure:
• wherein each occurrence of R30, when present, is independently selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 aminoalkyl, C3-C6 cycloalkyl, and C3-C6 heterocycloalkyl;
• wherein each occurrence of each of R22a and R22b, when present, is independently selected from hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, and —COR30;
• wherein R23, when present, is selected from hydrogen and C1-C4 alkyl;
• wherein R24, when present, is selected from C1-C4 alkyl, C1-C4 hydroxyalkyl, C1-C4 alkyl (C1-C4 alkoxy), C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-4 alkylamino(C1-C4 alkyl), (C1-C4)(C1-C4) dialkylamino(C1-C4 alkyl), —(CH2)r(C3-C6 cycloalkyl), and —(CH2)s(C3-C6 heterocycloalkyl);
• wherein r, when present, is selected from 0, 1, 2, and 3;
• wherein R6, when present, is selected from C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and —(CH2)sCy3;
• wherein s, when present, is selected from 0, 1, and 2;
• and
• wherein Cy3, when present, is selected from cycloalkyl, heterocycloalkyl, aryl, and heteroaryl and is substituted with 0-4 non-hydrogen groups independently selected from halogen, —OH, —CN, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 haloalkyl;
• or wherein each of R4a and R4b is hydrogen,
• provided that when o is 0 and Ar2 is monoaryl then Ar2 is substituted with at least one non-hydrogen group,
• or a pharmaceutically acceptable salt thereof.