Carboline derivatives

A compound having a formula

• wherein R0, independently, is selected from the group consisting of halo, C1-6alkyl, aryl, heteroaryl, C3-8cycloalkyl, C3-8heterocycloalkyl, C3-8cycloalkylQ, C(═O)Ra, OC(═O)Ra, C(═O)ORa, C1-4alkyleneNRaRb, C1-4alkyleneHet, C1-4alkyleneC(═O)ORa, C(═O)NRaSO2Rc, C(═O)C1-4alkyleneHet, C(═O)NRaRb, C(═O)NRbRc, C(═O)-NRaC1-4alkyleneORb, C(═O)NRaC1-4alkyleneHet, ORa, OC1-4alkyleneC(═O)ORa, OC1-4alkyleneNRaRb, OC1-4alkyleneHet, OC1-4alkyleneORa, OC1-4alkyleneNRaC(═O)ORb, NRaRb, NRbRc, NRaC1-4alkyleneNRaRb, NRaC(═O)Rb, NRaC(═O)NRaRb, N(SO2C1-4alkyl)2, NRa(SO2C1-4alkyl), nitro, trifluoromethyl, trifluoromethoxy, cyano, SO2NRaRb, SO2Ra, SORa, SRa, and OSO2CF3;
• R1 is selected from the group consisting of optionally substituted aryl, optionally substituted heteroaryl, an optionally substituted C3-8cycloalkyl ring, an optionally substituted C3-8heterocycloalkyl ring, an optionally substituted bicyclic ring
• wherein the fused ring B is a 5- or 6-membered ring, saturated or partially or fully unsaturated, and contains carbon atoms and optionally one to three heteroatoms selected from oxygen, sulfur, and nitrogen, hydrogen, arylC1-3alkyl, haloC1F-6alkyl, C1-4alkyleneC(═O)ORa, C1-4alkyleneC(═O)NRaRb, C3-8cycloalkyl, C3-8cycloalkenyl, C3-8heterocycloalkenyl, C1-4alkyleneHet, C1-4alkyleneQRa, C2-6alkenyleneQRa, C1-4alkyleneQC1-4alkyleneQRa,
• and a spiro substituent having a structure
• R2 is selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, C2-6alkenyl, C1-3alkylenearyl, arylC1-3alkyl, aryl, heteroaryl, C(═O)Ra, C(═O)NRaRb, C(═O)NRbRc, C(═S)NRaRb, C(═S)NRbRc, ORa, NRaRb, NRbRc, SO2Ra, SO2NRaRb, S(═O)Ra, S(═O)NRaRb, C(═O)NRaC1-4alkyleneORa, C(═O)NRaC1-4alkylene-Het, C(═O)C1-4alkylenearyl, C(═O)C1-4alkyleneheteroaryl, C1-4alkylenearyl, C1-4alkyleneheteroaryl, C1-4alkyleneHet, C1-4alkyleneC(═O)C1-4alkylenearyl, C1-4alkyleneC(═O)C1-4alkyleneheteroaryl, C1-4alkyleneC(═O)Het, C1-4alkyleneC(═O)NRbRc, C1-4alkyleneORa, C1-4alkyleneNRaC(═O)Ra, C1-4alkyleneOC1-4alkyleneORa, C1-4alkyleneNRbRc, C1-4alkyleneC(═O)ORa, and C1-4alkyleneOC1-4alkyleneC(═O)ORa;
• R3 is selected from the group consisting of hydrogen, C1-6alkyl, haloC1-6alkyl, aryl, heteroaryl, arylC1-3alkyl, heteroarylC1-3alkyl, C1-3alkylenearyl, C1-3alkyleneHet, C3-8cycloalkyl, and C3-8heterocycloalkyl;
• Y is selected from the group consisting of C(═O)Z, SO, C(═S), and CRa═CRa;
• Z is (CH2)t or C≡C;
• A is selected from the group consisting of furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,3-triazolyl, 1,3,4-thiadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3,4-oxatriazolyl, 1,2,3,5-oxatriazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-triazinyl, 1,2,4-triazinyl, 1,2,3-triazinyl, indolizinyl, indolyl, isoindolyl, benzo[b]furanyl, benzo[b]thienyl, 1H-indazolyl, benzimidazolyl, benzthiazoyl, purinyl, 4H-quinolizinyl, quinolinyl, isoquinolinyl, and naphthyl;
• R4 is selected from the group consisting of hydrogen, C1-6alkyl, aryl, heteroaryl, halo, C(═O)ORb, NHC(═O)C1-3alkyleneN(Rb)2, NO2, C(═O)ORb, ORb, CF3, ORa, CN, OC(═O)Rb, arylORb, Het, NRaC(═O)C1-3alkyleneC(═O)ORa, arylOC1-3alkyleneNRaRb, arylOC(═O)Ra, C1-4alkyleneC(═O)ORb, OC1-4alkyleneC(═O)ORb, C1-4alkyleneOC1-4alkyleneC(═O)ORb, C(═O)NRbSO2Rc, C1-4alkyleneNRbRc, C2-6alkenyleneNRbRc, C(═O)NRbC1-4alkyleneORb, C(═O)NRbC1-4alkyleneHet, OC2-4alkyleneNRbRc, OC1-4alkyleneCH(ORb)CH2NRbRc, OC1-4alkyleneHet, OC2-4alkyleneORb, OC2-4alkyleneNRbC(═O)ORc, NRbC1-4alkyleneNRbRc, NRbC(═O)Rc, NRbC(═O)NRbRc, N(SO2C1-4alkyl)2, NRb(SO2C1-4alkyl), SO2NRbRc, OSO2CF3, C(═O)Rb, C1-3alkylenearyl, C1-4alkyleneHet, C1-6alkyleneORb, C1-3alkyleneN(Rb)2, NRbRc, C(═O)NRbRc, NHC(═O)C1-3alkylenearyl, NHC(═O)C1-3alkyleneheteroaryl, C3-8cycloalkyl, C3-8heterocycloalkyl, arylOC1-3alkyleneN(Rb)2, arylOC(═O)Rb, NRC(═O)C1-3alkyleneC3-8heterocycloalkyl, NHC(═O)C1-3alkyleneHet, NHC(═O)haloC1-6alkyl, and
• R5, independently, is selected from the group consisting of halo, NRaRb, NO2, C1-6alkyl, oxo, and ORa;
• or R4 and R5 are taken together to form a 3- or 4-membered alkylene or alkenylene chain component of a 5- or 6-membered ring, optionally containing at least one heteroatom;
• Ra is selected from the group consisting of hydrogen, C1-6alkyl, cyano, aryl, arylC1-3alkyl, C1-3alkylenearyl, heteroaryl, heteroarylC1-3alkyl, and C1-3alkyleneheteroaryl;
• Rb is selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkyl, C1-3alkyleneN(Ra)2, aryl, arylC1-3alkyl, C1-3alkylenearyl, heteroaryl, heteroarylC1-3alkyl, and C1-3alkyleneheteroaryl;
• Rc is selected from the group consisting of hydrogen, C1-6alkyl, aryl, heteroaryl, arylC1-3alkyl, heteroarylC1-3alkyl, C1-3alkyleneN(Ra)2, C1-6alkylenearyl, C1-6alkyleneHet, haloC1-6alkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, Het, C1-3alkyleneheteroaryl, C1-6alkyleneC(═O)ORa, and C1-3alkyleneC3-8heterocycloalkyl;
• or Rb and Rc are taken together to form a 5- or 6-membered ring, optionally containing at least one heteroatom;
• Q is O, S, or NRd;
• C is O, S, or NRd;
• D is O, S, or NRa;
• E is CRa or N;
• F is CRa, C(Ra)2, or NRd;
• Rd is null or is selected from the group consisting of hydrogen, C1-6alkyl, aryl, heteroaryl, arylC1-3alkyl, heteroarylC1-3alkyl, C1-3alkylenearyl, and C1-3alkyleneheteroaryl;
• Het is a 5- or 6-membered heterocyclic ring, saturated or partially or fully unsaturated, containing at least one heteroatom selected from the group consisting of oxygen, nitrogen, and sulfur, and optionally substituted with C1-4alkyl or C(═O)ORa;
• n is 1;
• p is 0, 1, 2, or 3;
• q is 0, 1, 2, 3, or 4;
• t is 1, 2, 3, or 4;
• or a pharmaceutically acceptable salt or solvate thereof.