Novel Heterocyclic Compounds as Bromodomain Inhibitors

A compound of Formula III:

• or a stereoisomer, tautomer, pharmaceutical acceptable salt, or hydrate thereof,
• wherein:
• W2 is selected from N and CR4,
• W3 is selected from N and CR3,
• each W may be the same or different from each other;
• R1 is a carbocycle or heterocycle,
• R2 is selected from a 6-membered monocyclic carbocycle or monocyclic heterocycle,
• R3, R4, and R5 are each independently selected from hydrogen, alkyl, —OH, —NH2, thioalkyl, alkoxy, ketone, ester, carboxylic acid, urea, carbamate, carbonate, amino, amide, halogen, carbocycle, heterocycle, sulfone, sulfoxide, sulfide, sulfonamide, and —CN,
• with the proviso that R4 is not —OH and R5 is not —COON or -ester;
• R3 and R4 may be connected to form an optionally substituted 5-, 6-, or 7-membered carbocycle or heterocycle;
• R4 may be connected to B or R2 to form a carbocycle or heterocycle;
• X is selected from O and S;
• A is selected from —CRxRy—, C═O, —C(O)CRxRy—, —CRxRyCRzRv—, —SO2—, —CRxRyCRzRvO—, —CRxRyCRzRvN—, —CRxRyCRzRvS—, and —CRxRyCRzRvCRQRR—;
• with the proviso that Rx and Ry cannot both be an unsubstituted phenyl ring,
• and with the proviso that if A is —CH2CH2CH2— and W3 is N then R4 is not —OH,
• and with the proviso that if A is —CH2CH2O— then R1 is not
• Rx, Ry, Rz, Rv, RQ, and RR are each independently selected from hydrogen, alkyl(C1-C8), halogen, —OH, —CF3, amino, alkoxy (C1-C8), carboxyl, —CN, sulfone, sulfoxide, carbocycle, and heterocycle, or two substituents selected from Rx, Ry, Rz, Rv, RQ and RR may form an oxo or thio-oxo group, or two substituents selected from Rx, Ry, Rz, Rv, R5, and R1 may be connected in a 5- or 6-membered ring to form a bicyclic carbocycle or bicyclic heterocycle;
• B is selected from —(CRaRb)n—, —(CRaRbCRcRd)—, —O—, —OCRaRb—, —CRaRbO—, —NH—, —NHCRaRb—, —CRaRbNH—, —S—, —SCRaRb—, —CRaRbS—, —S(O)—, —S(O)CRaRb—, —CRaRbS(O)—, —SO2—, —SO2CRaRb—, and —CRaRbSO2—;
• n is selected from 0 and 1, meaning if n=0 then B is absent;
• and Ra, Rb, Rc, and Rd are each independently selected from hydrogen, alkyl(C1-C3), and alkoxy(C1-C3).

A compound of Formula IV:

• or a stereoisomer, tautomer, pharmaceutically acceptable salt, or hydrate thereof,
• wherein:
• W2 is selected from N and CR4,
• W3 is selected from N and CR3,
• each W may be the same or different from each other;
• R1 is a carbocycle or heterocycle,
• R2 is selected from a 6-membered monocyclic carbocycle or monocyclic heterocycle,
• R3 and R4 are each independently selected from hydrogen, alkyl, —OH, —NH2, thioalkyl, alkoxy, ketone, ester, carboxylic acid, urea, carbamate, carbonate, amino, amide, halogen, carbocycle, heterocycle, sulfone, sulfoxide, sulfide, sulfonamide, and —CN,
• with the proviso that R4 is not —OH;
• R3 and R4 may be connected to form an optionally substituted 5-, 6-, or 7-membered carbocycle or heterocycle,
• with the proviso that R3 and R4 are not connected to form
• R4 may be connected to B or R2 to form a carbocycle or heterocycle;
• X is selected from O and S;
• A is selected from —CRxRy—, C═O, —C(O)CRxRy—, —CRxRyCRzRv—, —SO2—, —CRxRyCRzRvO—, —CRxRyCRzRvN—, —CRxRyCRzRvS—, and —CRxRyCRzRvCRQRR—;
• with the proviso that if A is C═O, then R2 is not an optionally substituted
• where T is halogen,
• and with the proviso that Rx and Ry cannot both be an unsubstituted phenyl ring,
• and with the proviso that if A is —CH2CH2CH2— and W3 is N then R4 is not —OH,
• and with the proviso that if A is —CH2CH2O— then R1 is not
• Rx, Ry, Rz, Rv, RQ, and RR are each independently selected from hydrogen, alkyl(C1-C8), halogen, —OH, —CF3, amino, alkoxy (C1-C8), carboxyl, —CN, sulfone, sulfoxide, carbocycle, and heterocycle, or two substituents selected from Rx, Ry, Rz, Ry, RQ and RR may form an oxo or thio-oxo group, or
• two substituents selected from Rx, Ry, Rz, Rv, R5, and R1 may be connected in a 5- or 6-membered ring to form a bicyclic carbocycle or bicyclic heterocycle;
• B is selected from —(CRaRb)n—, —(CRaRbCRcRd)—, —O—, —OCRaRb—, —CRaRb—, —NH—, —NHCRaRb—, —CRaRbNH—, —S—, —SCRaRb—, —CRaRbS—, —S(O)—, —S(O)CRaRb—, —CRaRbS(O)—, —SO2—, —SO2CRaRb—, and —CRaRbSO2—;
• n is selected from 0 and 1, meaning if n=0 then B is absent;
• Ra, Rb, Rc, and Rd are each independently selected from hydrogen, alkyl(C1-C3), and alkoxy(C1-C3).