Condensed pyridoindole 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)Rb, OC(═O)Rb, C(═O)ORb, C1-4alkyleneNRbRc, C1-4alkyleneHet, C1-4alkyleneC(═O)ORb, C(═O)RbSO2Rd, C(═O)C1-4alkyleneHet, C(═O)NRbRc, C(═O)NRbRd, C(═O)NRbC1-4alkyleneORc, C(═O)NRbC1-4alkyleneHet, ORb, OC1-4alkyleneC(═O)ORb, OC1-4alkyleneNRbRc, OC1-4alkyleneHet, OC1-4alkyleneORb, OC1-4alkyleneNRbC(═O)ORc, NRbRc, NRbC1-4alkyleneNRbRc, NRbC(═O)RC, NRbC(═O)NRbRc, N(SO2C1-4alkyl)2, NRb(SO2C1-4alkyl), nitro, trifluoromethyl, trifluoromethoxy, cyano, SO2NRbRc, SO2Rb, SORb, SRb, and OSO2CF3;
• R1 is selected from the group consisting of aryl optionally substituted with one or more substituent selected from the group consisting of halo, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, haloalkyl, nitro, amino, alkylamino, acylamino, alkylthio, alkylsulfinyl, and alkylsulfonyl, heteroaryl optionally substituted with one or more substituent selected from the group consisting of halo, alkyl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, haloalkyl, nitro, amino, alkylamino, acylamino, alkylthio, alkylsulfinyl, and alkylsulfonyl, a C3-8cycloalkyl ring, a C3-8heterocycloalkyl ring, a bicyclic ring
• wherein the fused ring A is a 5- or 6-membered ring, saturated or partially or fully unsaturated, and comprises carbon atoms and optionally one to three heteroatoms selected from oxygen, sulfur, and nitrogen, hydrogen, arylC1-3alkyl, C1-3alkenylaryl, haloC1-6alkyl, C1-4alkyleneC(═O ORb, C1-4alkyleneC(═O NR Rc, C3-9cycloalkyl, C3-8cycloalkenyl, C3-8heterocycloalkenyl, C1-4alkyleneHet, C1-4alkyleneQRb, C2-6alkenyleneQRb, C1-4alkyleneQC1-4alkyleneQRb,
• and a spiro substituent having the structure
• R2 and R4, independently, are selected from the group consisting of hydrogen, C1-6alkyl, aryl, heteroaryl, arylC1-3alkyl, C1-3alkylenearyl, C1-3alkyleneHet, C3-8cycloalkyl, and C3-8heterocycloalkyl;
• R3 is selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkyl, C3-8heterocycloalkyl, C2-6alkenyl, C1-3alkylenearyl, arylC1-3alkyl, C(═O)Rb, aryl, heteroaryl, C(═O)Rb, C(═O)NRbRc, C(═O)NRbRd, C(═S)NRbRc, C(═S)NRbRd, SO2Rb, SO2NRbRc, S(═O)Rb, S(═O)NRbRc, C(═O)NRbC1-4alkyleneORb, C(═O)NRbC1-4alkyleneHet, C(═OC1-4alkylenearyl, C(═O)C1-4alkyleneheteroaryl, C1-4alkylenearyl substituted with one or more of SO2NRbRc, NRbRc, C(═O)ORb, NRbSO2CF3, CN, NO2, C(═O)Rb, ORb, C1-4alkyleneNRbRc, and OC1-4alkyleneNRbRc, C1-4alkyleneheteroaryl, C1-4alkyleneHet, C1-4alkyleneC(═O C1-4alkylenearyl, C1-4alkyleneC(═O C1-4alkyleneheteroaryl, C1-4alkyleneC(═O Het, C1-4alkyleneC(═O NRbRc, C1-4alkyleneORb, C1-4alkyleneNRbC(═O Rb, C1-4alkyleneOC1-4alkyleneORb, C1-4alkyleneNRbRc, C1-4alkyleneC(═O ORb, and C1-4alkyleneOC1-4alkyleneC(═O)ORb;
• X and Y, independently, are selected from the group consisting of C(═O), SO, SO2, C(═S), and C═C(Ra)2;
• Z is O, X, or C(Ra)2, or Z is NRd when X is SO, SO2, C(═S), or C═C(Ra)2 or Y is SO or SO2;
• Ra, independently, is selected from the group consisting of hydrogen, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, aryl, heteroaryl, arylC1-3alkyl, C1-3alkylenearyl, C(═O)ORb, C(═O)NRbRd, C1-4alkyleneNRbRc, halo, NO2, CF3, CF3O, ORb, OC(═O)Rb, OC1-4alkyleneC(═O ORb, C1-4alkyleneOC1-4alkyleneC(═O)ORb, C(═O NRbSO2Rd, C(═O)C1-4alkyleneHet, C2-6alkenyleneNRbRc, C(═O)NRaC1-4alkyleneORc, C(═O)NRbC1-4alkyleneHet, OC2-4alkyleneNRbRc, OC1-4alkyleneCH(ORb)CH2NRbRc, OC2-4alkyleneORb, OC2-4alkyleneNRbC(═O)ORc, NRbRc, NRbC1-4alkyleneNRbRc, NRbC(═O)Rc, NRbC(═O)NRbRc, N(SO2C1-4alkyl)2, NRb(SO2C1-4alkyl), SO2NRbRc, OSO2trifluoromethyl, C(═O)Rb, C1-3alkyleneORb, CN, and C1-6alkyleneC(═O)ORb;
• Rb is selected from the group consisting of hydrogen, C1-6alkyl, aryl, arylC1-3alkyl, C1-3alkylenearyl, heteroaryl, heteroarylC1-3alkyl, and C1-3alkyleneheteroaryl;
• Rc is selected from the group consisting of hydrogen, C1-6alkyl, C3-8cycloalkyl, C1-3alkyleneN(Rb)2, aryl, arylC1-3alkyl, C1-3alkylenearyl, and heteroaryl;
• Rd 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, C1-3alkyleneHet, C1-3alkyleneheteroaryl, C1-6alkyleneC(═O)ORa, and C1-3alkyleneC3-8heterocycloalkyl;
• or Rb and Rd are taken together to form a 5- or 6-membered ring, optionally containing at least one heteroatom;
• Ra is null or is selected from the group consisting of hydrogen, C1-6alkyl, aryl, heteroaryl, arylC1-3alkyl, heteroarylC1-3alkyl, C1-3alkylenearyl, and C1-3alkyleneheteroaryl;
• Q is O, S, or NRb;
• B is O, S, or NRe;
• C is O, S, or NRb;
• D is CRb or N;
• E is CRb, C(Ra)2, or NRe;
• Het represents 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)ORb;
• q is 0, 1, 2, 3, or 4;
• and
• pharmaceutically acceptable salts and hydrates thereof,
• wherein heteroaryl is a monocyclic or bicyclic ring system having one or two aromatic rings and five to ten atoms, with at least one nitrogen, oxygen, or sulfur atom in an aromatic ring,
• and wherein C3-8heterocycloalkyl has one or more heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur.