Heterobicyclic metalloprotease inhibitors

A compound having the structure:

• wherein:
• R1 in each occurrence is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, and heterocycloalkyl fused heteroarylalkyl,
• wherein R1 is optionally substituted one or more times, or
• wherein R1 is optionally substituted by one R16 group and optionally substituted by one or more R9 groups;
• R2 in each occurrence is independently selected from hydrogen and alkyl, wherein alkyl is optionally substituted one or more times or R1 and R2 when taken together with the nitrogen to which they are attached complete a 3- to 8-membered ring containing carbon atoms and optionally containing a heteroatom selected from O, S(O)x, or NR50 and which is optionally substituted one or more times;
• R3 is selected from
• R4 in each occurrence is independently selected from R10, hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, halo, haloalkyl, CF3, (C0-C6)-alkyl-COR10, (C0-C6)-alkyl-OR10, (C0-C6)-alkyl-NR10R11, (C0-C6)-alkyl-NO2, (C0-C6)-alkyl-CN, (C0-C6)-alkyl-S(O)yOR0, (C0-C6)-alkyl-S(O)yNR10R11, (C0-C6)-alkyl-NR10CONR11SO2R30, (C0-C6)-alkyl-S(O)yR10, (C0-C6)-alkyl-OC(O)R10, (C0-C6)-alkyl-OC(O)NR10R11, (C0-C6)-alkyl-C(═NR10)NR10R11, (C0-C6)-alkyl-NR10C(═NR11)NR10R11, (C0-C6)-alkyl-C(O)OR10, (C0-C6)-alkyl-C(O)NR10R11, (C0-C6)-alkyl-C(O)NR10SO2R11, (C0-C6)-alkyl-C(O)—NR11—CN, O—(C0-C6)-alkyl-C(O)NR10R11, S(O)x—(C0-C6)-alkyl-C(O)OR10, S(O), —(C0-C6)-alkyl-C(O)NR10R11, (C0-C6)-alkyl-C(O)NR10—(C0-C6)-alkyl-NR10R11, (C0-C6)-alkyl-NR10—C(O)R10, (C0-C6)-alkyl-NR10—C(O)OR10, (C0-C6)-alkyl-NR10—C(O)—NR10R11, (C0-C6)-alkyl-NR10—S(O)yNR10R11, (C0-C6)-alkyl-NR10—S(O)yR0, O—(C0-C6)-alkyl-aryl and O—(C0-C6)-alkyl-heteroaryl,
• wherein each R4 group is optionally substituted one or more times, or
• wherein each R4 group is optionally substituted by one or more R14 groups;
• R5 in each occurrence is independently selected from hydrogen, alkyl, C(O)NR10R11, aryl, arylalkyl, SO2NR10R11 and C(O)OR10, wherein alkyl, aryl and arylalkyl are optionally substituted one or more times;
• R9 in each occurrence is independently selected from R10, hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, halo, CHF2, CF3, OR10, SR10, COOR10, CH(CH3)CO2H, (C0-C6)-alkyl-COR10, (C0-C6)-alkyl-OR10, (C0-C6)-alkyl-NR10R11, (C0-C6)-alkyl-NO2, (C0-C6)-alkyl-CN, (C0-C6)-alkyl-S(O)yOR10, (C0-C6)-alkyl-P(O)2OH, (C0-C6)-alkyl-S(O)yNR10R11, (C0-C6)-alkyl-NR10CONR1SO2R3e, (C0-C6)-alkyl-S(O)xR10, (C0-C6)-alkyl-OC(O)R10, (C0-C6)-alkyl-OC(O)NR10R11, (C0-C6)-alkyl-C(═NR10)NR10R11, (C0-C6)-alkyl-NR10C(═NR11)NR10R11, (C0-C6)-alkyl-NR10C(═N—CN)NR10R11, (C0-C6)-alkyl-C(═N—CN)NR10R11, (C0-C6)-alkyl-NR10C(═N—NO2)NR10R11, (C0-C6)-alkyl-C(═N—NO2)NR10R11, (C0-C6)-alkyl-C(O)OR10, (C0-C6)-alkyl-C(O)NR10R11, (C0-C6)-alkyl-C(O)NR10SO2R11, C(O)NR10—(C0-C6)-alkyl-heteroaryl, C(O)NR10—(C0-C6)-alkyl-aryl, S(O)2NR10—(C0-C6)-alkyl-aryl, S(O)2NR10—(C0-C6)-alkyl-heteroaryl, S(O)2NR10-alkyl, S(O)2—(C0-C6)-alkyl-aryl, S(O)2—(C0-C6)-alkyl-heteroaryl, (C0-C6)-alkyl-C(O)—NR11—CN, O—(C0-C6)-alkyl-C(O)NR10R11, S(O), —(C0-C6)-alkyl-C(O)OR10, S(O), —(C0-C6)-alkyl-C(O)NR10R11, (C0-C6)-alkyl-C(O)NR10—(C0-C6)-alkyl-NR10R11, (C0-C6)-alkyl-NR10—C(O)R10, (C0-C6)-alkyl-NR10—C(O)OR10, (C0-C6)-alkyl-NR10—C(O)—NR10R11, (C0-C6)-alkyl-NR10—S(O)yNR10R11, (C0-C6)-alkyl-NR10—S(O)yR11, O—(C0-C6)-alkyl-aryl and O—(C0-C6)-alkyl-heteroaryl,
• wherein each R9 group is optionally substituted, or
• wherein each R9 group is optionally substituted by one or more R14 groups;
• R10 and R11 in each occurrence are independently selected from hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, and heterocycloalkyl fused heteroarylalkyl, wherein alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, and heterocycloalkyl fused heteroarylalkyl are optionally substituted one or more times, or when R10 and R11 are attached to a nitrogen atom they may be taken together to complete a 3- to 8-membered ring containing carbon atoms and optionally containing a heteroatom selected from O, S, or NR50 and which is optionally substituted one or more times;
• R14 is independently selected from hydrogen, alkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, heterocyclylalkyl and halo, wherein alkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl and heterocyclylalkyl are optionally substituted one or more times.
• R16 is selected from cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, heterocycloalkyl fused heteroarylalkyl, (i) and (ii):
• wherein cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, and heterocycloalkyl fused heteroarylalkyl are optionally substituted one or more times;
• R20 is selected from selected from hydrogen, alkyl, heteroalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, fluoroalkyl, heterocycloalkylalkyl, haloalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and aminoalkyl, wherein alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, fluoroalkyl, heterocycloalkylalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and aminoalkyl are optionally substituted one or more times, or when R20 and R21 are attached to a nitrogen atom they may be taken together to complete a 3- to 8-membered ring containing carbon atoms and optionally containing a heteroatom selected from O, S, or NR50 and which is optionally substituted one or more times;
• R21 is a monocyclic, bicyclic or tricyclic ring system wherein said bicyclic or tricyclic ring system is fused and contains at least one ring which is partially saturated and
• wherein R21 is optionally substituted one or more times, or
• wherein R21 is optionally substituted by one or more R9 groups;
• R22 is independently selected from hydrogen, halo, alkyl, cycloalkyl, hydroxy, alkoxy, aryl, heteroaryl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, NO2, NR10R11, NR10NR10R11, NR10N═CR10R11, NR10SO2R11, CN, C(O)OR10, and fluoroalkyl, wherein alkyl, cycloalkyl, alkoxy, alkenyl, alkynyl and fluoroalkyl are optionally substituted one or more times;
• R30 is selected from alkyl and (C0-C6)-alkyl-aryl, wherein alkyl and aryl are optionally substituted;
• R50 in each occurrence is independently selected from hydrogen, alkyl, aryl, heteroaryl, C(O)R80, C(O)NR80R81, SO2R80 and SO2NR80R81, wherein alkyl, aryl, and heteroaryl are optionally substituted one or more times;
• R51 is independently selected from hydrogen, alkyl, aryl, heteroaryl, arylalkyl, cycloalkylalkyl, heteroarylalkyl and haloalkyl, wherein alkyl, aryl, heteroaryl, arylalkyl, cycloalkylalkyl, heteroarylalkyl and haloalkyl are optionally substituted one or more times;
• R52 is selected from hydrogen, halo, CN, hydroxy, alkoxy, fluoroalkoxy, alkyl, aryl, heteroaryl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, haloalkyl, C(O)NR10R11 and SO2NR10R11, wherein alkoxy, fluoroalkoxy, alkyl, aryl, heteroaryl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, and haloalkyl are optionally substituted one or more times;
• R80 and R81 are independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, fluoroalkyl, heterocycloalkylalkyl, haloalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and aminoalkyl, wherein alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, fluoroalkyl, heterocycloalkylalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and aminoalkyl are optionally substituted one or more times, or R80 and R81 when taken together with the nitrogen to which they are attached complete a 3- to 8-membered ring containing carbon atoms and optionally a heteroatom selected from O, S(O)x, —NH, and —N(alkyl) and which is optionally substituted one or more times;
• E is selected from a bond, CR10R11, O, NR5, S, S═O, S(═O)2, C(═O), N(R10)(C═O), (C═O)N(R10), N(R10)S(═O)2, S(═O)2N(R10), C═N—OR11, —C(R10R11)C(R10R11)—, —CH2—W1— and
• D is a member selected from CR22 and N;
• La is selected from CR9 and N;
• Lb is independently selected from C and N with the provisos that both Lb are not N, and that the bond between Lb and Lb is optionally a double bond only if both are Lb are carbon;
• Q is a 5- or 6-membered ring selected from aryl and heteroaryl, wherein aryl and heteroaryl are optionally substituted one or more times with R4;
• U is selected from C(R5R10), NR5, O, S, S═O and S(═O)2;
• W1 is selected from O, NR5, S, S═O, S(═O)2, N(R10)(C═O), N(R10)S(═O)2 and S(═O)2N(R10);
• X is selected from a bond and (CR10R11)wE(CR10R11)w;
• X1 is a bond, NR10, CH2, CHR20, CR20R21, SO2, SO, S, PO2, O, C═S, C═NR1, C═N—SO2R10, C═N—CN, C═N—CONR10R11, C═N—COR10, C═N—OR10;
• g and h are independently selected from 0-2;
• w is independently selected from 0-4;
• x is selected from 0 to 2;
• y is selected from 1 and 2;
• and
• N-oxides, pharmaceutically acceptable salts, prodrugs, formulations, polymorphs, tautomers, racemic mixtures and stereoisomers thereof.

A compound having the structure:

• wherein:
• R1 in each occurrence is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiralkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, and heterocycloalkyl fused heteroarylalkyl,
• wherein R1 is optionally substituted one or more times, or
• wherein R1 is optionally substituted by one R16 group and optionally substituted by one or more R9 groups;
• R2 in each occurrence is independently selected from hydrogen and alkyl, wherein alkyl is optionally substituted one or more times or R1 and R2 when taken together with the nitrogen to which they are attached complete a 3- to 8-membered ring containing carbon atoms and optionally containing a heteroatom selected from O, S(O)x, or NR50 and which is optionally substituted one or more times;
• R3 is SO2NR10R11, SO2NR20R21, PO2R10, PO2R1,
• R4 in each occurrence is independently selected from R10, hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, halo, haloalkyl, CF3, (C0-C6)-alkyl-COR10, (C0-C6)-alkyl-OR10, (C0-C6)-alkyl-NR10R11, (C0-C6)-alkyl-NO2, (C0-C6)-alkyl-CN, (C0-C6)-alkyl-S(O)yOR10, (C0-C6)-alkyl-S(O)yNR10R11, (C0-C6)-alkyl-NR10CONR11SO2R30, (C0-C6)-alkyl-S(O)yR10, (C0-C6)-alkyl-OC(O)R10, (C0-C6)-alkyl-OC(O)NR10R11, (C0-C6)-alkyl-C(═NR10)NR10R11, (C0-C6)-alkyl-NR10C(═NR11)NR10R11, (C0-C6)-alkyl-C(O)OR10, (C0-C6)-alkyl-C(O)NR10R11, (C0-C6)-alkyl-C(O)NR10SO2R11, (C0-C6)-alkyl-C(O)—NR11—CN, O—(C0-C6)-alkyl-C(O)NR10R11, S(O)x—(C0-C6)-alkyl-C(O)OR10, S(O), —(C0-C6)-alkyl-C(O)NR10R11, (C0-C6)-alkyl-C(O)NR10—(C0-C6)-alkyl-NR10R11, (C0-C6)-alkyl-NR10—C(O)R10, (C0-C6)-alkyl-NR10—C(O)OR10, (C0-C6)-alkyl-NR10—C(O)—NR10R11, (C0-C6)-alkyl-NR10—S(O)yNR10R11, (C0-C6)-alkyl-NR10—S(O)yR10, O—(C0-C6)-alkyl-aryl and O—(C0-C6)-alkyl-heteroaryl,
• wherein each R4 group is optionally substituted one or more times, or
• wherein each R4 group is optionally substituted by one or more R14 groups;
• R5 in each occurrence is independently selected from hydrogen, alkyl, C(O)NR10R11, aryl, arylalkyl, SO2NR10R11 and C(O)OR10, wherein alkyl, aryl and arylalkyl are optionally substituted one or more times;
• R9 in each occurrence is independently selected from R10, hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, halo, CHF2, CF3, OR10, SR10, COOR10, CH(CH3)CO2H, (C0-C6)-alkyl-COR10, (C0-C6)-alkyl-OR10, (C0-C6)-alkyl-NR10R11, (C0-C6)-alkyl-NO2, (C0-C6)-alkyl-CN, (C0-C6)-alkyl-S(O)yOR10, (C0-C6)-alkyl-P(O)2OH, (C0-C6)-alkyl-S(O)yNR10R11, (C0-C6)-alkyl-NR10CONR11SO2R30, (C0-C6)-alkyl-S(O)xR10, (C0-C6)-alkyl-OC(O)R10, (C0-C6)-alkyl-OC(O)NR10R11, (C0-C6)-alkyl-C(═NR10)NR10R11, (C0-C6)-alkyl-NR10C(═NR11)NR10R11, (C0-C6)-alkyl-NR10C(═N—CN)NR10R11, (C0-C6)-alkyl-C(═N—CN)NR10R11, (C0-C6)-alkyl-NR10C(═N—NO2)NR10R11, (C0-C6)-alkyl-C(═N—NO2)NR10R11, (C0-C6)-alkyl-C(O)OR10, (C0-C6)-alkyl-C(O)NR10R11, (C0-C6)-alkyl-C(O)NR10SO2R11, C(O)NR10—(C0-C6)-alkyl-heteroaryl, C(O)NR10—(C0-C6)-alkyl-aryl, S(O)2NR10—(C0-C6)-alkyl-aryl, S(O)2NR10—(C0-C6)-alkyl-heteroaryl, S(O)2NR10-alkyl, S(O)2—(C0-C6)-alkyl-aryl, S(O)2—(C0-C6)-alkyl-heteroaryl, (C0-C6)-alkyl-C(O)—NR10—CN, O—(C0-C6)-alkyl-C(O)NR10R11, S(O)x—(C0-C6)-alkyl-C(O)OR10, S(O)x—(C0-C6)-alkyl-C(O)NR10R11, (C0-C6)-alkyl-C(O)NR10—(C0-C6)-alkyl-NR10R11, (C0-C6)-alkyl-NR10—C(O)R10, (C0-C6)-alkyl-NR10—C(O)OR10, (C0-C6)-alkyl-NR10—C(O)—NR10R11, (C0-C6)-alkyl-NR10—S(O)yNR10R11, (C0-C6)-alkyl-NR10—S(O)yR10, O—(C0-C6)-alkyl-aryl and O—(C0-C6)-alkyl-heteroaryl,
• wherein each R9 group is optionally substituted, or
• wherein each R9 group is optionally substituted by one or more R14 groups;
• R10 and R11 in each occurrence are independently selected from hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, and heterocycloalkyl fused heteroarylalkyl, wherein alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, and heterocycloalkyl fused heteroarylalkyl are optionally substituted one or more times, or when R10 and R11 are attached to a nitrogen atom they may be taken together to complete a 3- to 8-membered ring containing carbon atoms and optionally containing a heteroatom selected from O, S, or NR50 and which is optionally substituted one or more times;
• R14 is independently selected from hydrogen, alkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, heterocyclylalkyl and halo, wherein alkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl and heterocyclylalkyl are optionally substituted one or more times.
• R16 is selected from cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, heterocycloalkyl fused heteroarylalkyl, (i) and (ii):
• wherein cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, and heterocycloalkyl fused heteroarylalkyl are optionally substituted one or more times;
• R20 is selected from selected from hydrogen, alkyl, heteroalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, fluoroalkyl, heterocycloalkylalkyl, haloalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and aminoalkyl, wherein alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, fluoroalkyl, heterocycloalkylalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and aminoalkyl are optionally substituted one or more times, or when R20 and R2 are attached to a nitrogen atom they may be taken together to complete a 3- to 8-membered ring containing carbon atoms and optionally containing a heteroatom selected from O, S, or NR50 and which is optionally substituted one or more times;
• R21 is a monocyclic, bicyclic or tricyclic ring system wherein said bicyclic or tricyclic ring system is fused and contains at least one ring which is partially saturated and
• wherein R21 is optionally substituted one or more times, or
• wherein R21 is optionally substituted by one or more R9 groups;
• R22 is independently selected from hydrogen, halo, alkyl, cycloalkyl, hydroxy, alkoxy, aryl, heteroaryl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, NO2, NR10R11, NR10NR10R11, NR10N═CR10R11, NR10SO2R11, CN, C(O)OR10, and fluoroalkyl, wherein alkyl, cycloalkyl, alkoxy, alkenyl, alkynyl and fluoroalkyl are optionally substituted one or more times;
• R30 is selected from alkyl and (C0-C6)-alkyl-aryl, wherein alkyl and aryl are optionally substituted;
• R50 in each occurrence is independently selected from hydrogen, alkyl, aryl, heteroaryl, C(O)R80, C(O)NR80R81, SO2R80 and SO2NR81R81, wherein alkyl, aryl, and heteroaryl are optionally substituted one or more times;
• R51 is independently selected from hydrogen, alkyl, aryl, heteroaryl, arylalkyl, cycloalkylalkyl, heteroarylalkyl and haloalkyl, wherein alkyl, aryl, heteroaryl, arylalkyl, cycloalkylalkyl, heteroarylalkyl and haloalkyl are optionally substituted one or more times;
• R52 is selected from hydrogen, halo, CN, hydroxy, alkoxy, fluoroalkoxy, alkyl, aryl, heteroaryl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, haloalkyl, C(O)NR10R11 and SO2NR10R11, wherein alkoxy, fluoroalkoxy, alkyl, aryl, heteroaryl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, and haloalkyl are optionally substituted one or more times;
• R80 and R81 are independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, fluoroalkyl, heterocycloalkylalkyl, haloalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and aminoalkyl, wherein alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, fluoroalkyl, heterocycloalkylalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and aminoalkyl are optionally substituted one or more times, or R80 and R81 taken together with the nitrogen to which they are attached complete a 3- to 8-membered ring containing carbon atoms and optionally a heteroatom selected from O, S(O)x, —NH, and —N(alkyl) and which is optionally substituted one or more times;
• E is selected from a bond, CR10R11, O, NR5, S, S═O, S(═O)2, C(═O), N(R10)(C═O), (C═O)N(R10), N(R10)S(═O)2, S(═O)2N(R10), C═N—OR11, —C(R10R11)C(R10R11)—, —CH2—W1— and
• D is a member selected from CR22 and N;
• La is selected from CR9 and N;
• Lb is independently selected from C and N with the provisos that both Lb are not N, and that the bond between Lb and Lb is optionally a double bond only if both are Lb are carbon;
• Q is a 5- or 6-membered ring selected from aryl and heteroaryl, wherein aryl and heteroaryl are optionally substituted one or more times with R4;
• U is selected from C(R5R10), NR5, O, S, S═O and S(═O)2;
• W1 is selected from O, NR5, S, S═O, S(═O)2, N(R10)(C═O), N(R10)S(═O)2 and S(═O)2N(R10);
• X is selected from a bond and (CR10R11)wE(CR10R11)w;
• X1 is a bond, NR10, CH2, CHR20, CR20R21, SO2, SO, S, PO2, O, C═S, C═NR1, C═N—SO2R10, C═N—CN, C═N—CONR10R11, C═N—COR10, C═N—OR10;
• g and h are independently selected from 0-2;
• w is independently selected from 0-4;
• x is selected from 0 to 2;
• y is selected from 1 and 2;
• and
• N-oxides, pharmaceutically acceptable salts, prodrugs, formulations, polymorphs, tautomers, racemic mixtures and stereoisomers thereof.

A compound having the structure:

• wherein:
• R1 in each occurrence is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, and heterocycloalkyl fused heteroarylalkyl,
• wherein R1 is optionally substituted one or more times, or
• wherein R1 is optionally substituted by one R16 group and optionally substituted by one or more R9 groups;
• R2 in each occurrence is independently selected from hydrogen and alkyl, wherein alkyl is optionally substituted one or more times or R1 and R2 when taken together with the nitrogen to which they are attached complete a 3- to 8-membered ring containing carbon atoms and optionally containing a heteroatom selected from O, S(O)x, or NR50 and which is optionally substituted one or more times;
• R4 in each occurrence is independently selected from R10, hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, halo, haloalkyl, CF3, (C0-C6)-alkyl-COR10, (C0-C6)-alkyl-OR10, (C0-C6)-alkyl-NR10R11, (C0-C6)-alkyl-NO2, (C0-C6)-alkyl-CN, (C0-C6)-alkyl-S(O)yOR10, (C0-C6)-alkyl-S(O)yNR10R11, (C0-C6)-alkyl-NR10CONR11SO2R30, (C0-C6)-alkyl-S(O)xR10, (C0-C6)-alkyl-OC(O)R10, (C0-C6)-alkyl-OC(O)NR10R11, (C0-C6)-alkyl-C(═NR10)NR10R11, (C0-C6)-alkyl-NR10C(═NR11)NR10R11, (C0-C6)-alkyl-C(O)OR10, (C0-C6)-alkyl-C(O)NR10R11, (C0-C6)-alkyl-C(O)NR10SO2R11, (C0-C6)-alkyl-C(O)—NR11—CN, O—(C0-C6)-alkyl-C(O)NR10R11, S(O)x—(C0-C6)-alkyl-C(O)OR10, S(O), —(C0-C6)-alkyl-C(O)NR10R11, (C0-C6)-alkyl-C(O)NR10—(C0-C6)-alkyl-NR10R11, (C0-C6)-alkyl-NR10—C(O)R10, (C0-C6)-alkyl-NR10—C(O)OR10, (C0-C6)-alkyl-NR10—C(O)—NR10R11, (C0-C6)-alkyl-NR10—S(O)yNR10R11, (C0-C6)-alkyl-NR10—S(O)yR10, O—(C0-C6)-alkyl-aryl and O—(C0-C6)-alkyl-heteroaryl,
• wherein each R4 group is optionally substituted one or more times, or
• wherein each R4 group is optionally substituted by one or more R14 groups;
• R5 in each occurrence is independently selected from hydrogen, alkyl, C(O)NR10R11, aryl, arylalkyl, SO2NR10R11 and C(O)OR10, wherein alkyl, aryl and arylalkyl are optionally substituted one or more times;
• R9 in each occurrence is independently selected from R10, hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, halo, CHF2, CF3, OR10, SR10, COOR10, CH(CH3)CO2H, (C0-C6)-alkyl-COR10, (C0-C6)-alkyl-OR10, (C0-C6)-alkyl-NR10R11, (C0-C6)-alkyl-NO2, (C0-C6)-alkyl-CN, (C0-C6)-alkyl-S(O)yOR10, (C0-C6)-alkyl-P(O)2OH, (C0-C6)-alkyl-S(O)xNR10R11, (C0-C6)-alkyl-NR10CONR11SO2R30, (C0-C6)-alkyl-S(O)xR10, (C0-C6)-alkyl-OC(O)R10, (C0-C6)-alkyl-OC(O)NR10R11, (C0-C6)-alkyl-C(═NR10)NR10R11, (C0-C6)-alkyl-NR10C(═NR11)NR10R11, (C0-C6)-alkyl-NR10C(═N—CN)NR10R11, (C0-C6)-alkyl-C(═N—CN)NR10R11, (C0-C6)-alkyl-NR10C(═N—NO2)NR10R11, (C0-C6)-alkyl-C(═N—NO2)NR10R11, (C0-C6)-alkyl-C(O)OR10, (C0-C6)-alkyl-C(O)NR10R11, (C0-C6)-alkyl-C(O)NR10SO2R11, C(O)NR10—(C0-C6)-alkyl-heteroaryl, C(O)NR10—(C0-C6)-alkyl-aryl, S(O)2NR10—(C0-C6)-alkyl-aryl, S(O)2NR10—(C0-C6)-alkyl-heteroaryl, S(O)2NR10-alkyl, S(O)2—(C0-C6)-alkyl-aryl, S(O)2—(C0-C6)-alkyl-heteroaryl, (C0-C6)-alkyl-C(O)—NR10—CN, O—(C0-C6)-alkyl-C(O)NR10R11, S(O)x—(C0-C6)-alkyl-C(O)OR10, S(O), —(C0-C6)-alkyl-C(O)NR10R11, (C0-C6)-alkyl-C(O)NR10—(C0-C6)-alkyl-NR10R11, (C0-C6)-alkyl-NR10—C(O)R10, (C0-C6)-alkyl-NR10—C(O)OR10, (C0-C6)-alkyl-NR10—C(O)—NR10R11, (C0-C6)-alkyl-NR10—S(O)yNR10R11, (C0-C6)-alkyl-NR10—S(O)yR11, O—(C0-C6)-alkyl-aryl and O—(C0-C6)-alkyl-heteroaryl,
• wherein each R9 group is optionally substituted, or
• wherein each R9 group is optionally substituted by one or more R14 groups;
• R10 and R11 in each occurrence are independently selected from hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, and heterocycloalkyl fused heteroarylalkyl, wherein alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, and heterocycloalkyl fused heteroarylalkyl are optionally substituted one or more times, or when R10 and R11 are attached to a nitrogen atom they may be taken together to complete a 3- to 8-membered ring containing carbon atoms and optionally containing a heteroatom selected from O, S, or NR50 and which is optionally substituted one or more times;
• R14 is independently selected from hydrogen, alkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, heterocyclylalkyl and halo, wherein alkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl and heterocyclylalkyl are optionally substituted one or more times.
• R16 is selected from cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, heterocycloalkyl fused heteroarylalkyl, (i) and (ii):
• wherein cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, and heterocycloalkyl fused heteroarylalkyl are optionally substituted one or more times;
• R20 is selected from selected from hydrogen, alkyl, heteroalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, fluoroalkyl, heterocycloalkylalkyl, haloalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and aminoalkyl, wherein alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, fluoroalkyl, heterocycloalkylalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and aminoalkyl are optionally substituted one or more times, or when R20 and R21 are attached to a nitrogen atom they may be taken together to complete a 3- to 8-membered ring containing carbon atoms and optionally containing a heteroatom selected from O, S, or NR50 and which is optionally substituted one or more times;
• R21 is a monocyclic, bicyclic or tricyclic ring system wherein said bicyclic or tricyclic ring system is fused and contains at least one ring which is partially saturated and
• wherein R21 is optionally substituted one or more times, or
• wherein R21 is optionally substituted by one or more R9 groups;
• R22 is independently selected from hydrogen, halo, alkyl, cycloalkyl, hydroxy, alkoxy, aryl, heteroaryl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, NO2, NR10R11, NR10NR10R11, NR10N═CR10R11, NR10SO2R11, CN, C(O)OR10, and fluoroalkyl, wherein alkyl, cycloalkyl, alkoxy, alkenyl, alkynyl and fluoroalkyl are optionally substituted one or more times;
• R30 is selected from alkyl and (C0-C6)-alkyl-aryl, wherein alkyl and aryl are optionally substituted;
• R50 in each occurrence is independently selected from hydrogen, alkyl, aryl, heteroaryl, C(O)R80, C(O)NR80R81, SO2R80 and SO2NR80R81, wherein alkyl, aryl, and heteroaryl are optionally substituted one or more times;
• R51 is independently selected from hydrogen, alkyl, aryl, heteroaryl, arylalkyl, cycloalkylalkyl, heteroarylalkyl and haloalkyl, wherein alkyl, aryl, heteroaryl, arylalkyl, cycloalkylalkyl, heteroarylalkyl and haloalkyl are optionally substituted one or more times;
• R52 is selected from hydrogen, halo, CN, hydroxy, fluoroalkoxy, alkyl and haloalkyl;
• R80 and R81 are independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, fluoroalkyl, heterocycloalkylalkyl, haloalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and aminoalkyl, wherein alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, fluoroalkyl, heterocycloalkylalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and aminoalkyl are optionally substituted one or more times, or R80 and R81 when taken together with the nitrogen to which they are attached complete a 3- to 8-membered ring containing carbon atoms and optionally a heteroatom selected from O, S(O)x, —NH, and —N(alkyl) and which is optionally substituted one or more times;
• E is selected from a bond, CR10R11, O, NR5, S, S═O, S(═O)2, C(═O), N(R10)(C═O), (C═O)N(R10), N(R10)S(═O)2, S(═O)2N(R10), C═N—OR11, —C(R10R11)C(R10R11)—, —CH2—W1— and
• D is a member selected from CR22 and N;
• L is C or N;
• U is selected from C(R5R10), NR5, O, S, S═O and S(═O)2;
• W1 is selected from O, NR5, S, S═O, S(═O)2, N(R10)(C═O), N(R10)S(═O)2 and S(═O)2N(R10);
• X is selected from a bond and (CR10R11)wE(CR10R11)w;
• X1 is a bond, NR10, CH2, CHR20, CR20R21, SO2, SO, S, PO2, O, C═S, C═NR1, C═N—SO2R10, C═N—CN, C═N—CONR10R11, C═N—COR10, C═N—OR10;
• g and h are independently selected from 0-2;
• w is independently selected from 0-4;
• x is selected from 0 to 2;
• y is selected from 1 and 2;
• and
• N-oxides, pharmaceutically acceptable salts, prodrugs, formulations, polymorphs, tautomers, racemic mixtures and stereoisomers thereof.

A compound having the structure:

• wherein:
• R1 in each occurrence is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, and heterocycloalkyl fused heteroarylalkyl,
• wherein R1 is optionally substituted one or more times, or
• wherein R1 is optionally substituted by one R16 group and optionally substituted by one or more R9 groups;
• R2 in each occurrence is independently selected from hydrogen and alkyl, wherein alkyl is optionally substituted one or more times or R1 and R2 when taken together with the nitrogen to which they are attached complete a 3- to 8-membered ring containing carbon atoms and optionally containing a heteroatom selected from O, S(O)x, or NR50 and which is optionally substituted one or more times;
• R3 is NR20R21, NR10R11, NR10SO2R10, NR10SO2R11, OR10, OR21 or NR10NR9;
• R4 in each occurrence is independently selected from R10, hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, halo, haloalkyl, CF3, (C0-C6)-alkyl-COR10, (C0-C6)-alkyl-OR10, (C0-C6)-alkyl-NR10R11, (C0-C6)-alkyl-NO2, (C0-C6)-alkyl-CN, (C0-C6)-alkyl-S(O)yOR10, (C0-C6)-alkyl-S(O)yNR10R11, (C0-C6)-alkyl-NR10CONR11SO2R30, (C0-C6)-alkyl-S(O)xR10, (C0-C6)-alkyl-OC(O)R10, (C0-C6)-alkyl-OC(O)NR10R11, (C0-C6)-alkyl-C(═NR10)NR10R11, (C0-C6)-allyl-NR10C(═NR11)NR10R11, (C0-C6)-alkyl-C(O)OR10, (C0-C6)-alkyl-C(O)NR10R11, (C0-C6)-alkyl-C(O)NR10SO2R11, (C0-C6)-alkyl-C(O)—NR11—CN, O—(C0-C6)-alkyl-C(O)NR10R11, S(O)x—(C0-C6)-alkyl-C(O)OR10, S(O)x—(C0-C6)-alkyl-C(O)NR10R11, (C0-C6)-alkyl-C(O)NR10—(C0-C6)-alkyl-NR10R11, (C0-C6)-alkyl-NR10—C(O)R10, (C0-C6)-alkyl-NR10—C(O)OR10, (C0-C6)-alkyl-NR10—C(O)—NR10R11, (C0-C6)-alkyl-NR10—S(O)yNR10R11, (C0-C6)-alkyl-NR10—S(O)yR10, O—(C0-C6)-alkyl-aryl and O—(C0-C6)-alkyl-heteroaryl,
• wherein each R4 group is optionally substituted one or more times, or
• wherein each R4 group is optionally substituted by one or more R14 groups;
• R5 in each occurrence is independently selected from hydrogen, alkyl, C(O)NR10R11, aryl, arylalkyl, SO2NR10R11 and C(O)OR10, wherein alkyl, aryl and arylalkyl are optionally substituted one or more times;
• R9 in each occurrence is independently selected from R10, hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, halo, CHF2, CF3, OR10, SR10, COOR10, CH(CH3)CO2H, (C0-C6)-alkyl-COR10, (C0-C6)-alkyl-OR10, (C0-C6)-alkyl-NR10R11, (C0-C6)-alkyl-NO2, (C0-C6)-alkyl-CN, (C0-C6)-alkyl-S(O)yOR10, (C0-C6)-alkyl-P(O)2OH, (C0-C6)-alkyl-S(O)yNR10R11, (C0-C6)-alkyl-NR10CONR11SO2R30, (C0-C6)-alkyl-S(O)xR10, (C0-C6)-alkyl-OC(O)R10, (C0-C6)-alkyl-OC(O)NR10R11, (C0-C6)-alkyl-C(═NR10)NR10R11, (C0-C6)-alkyl-NR10C(═NR11)NR10R11, (C0-C6)-alkyl-NR10C(═N—CN)NR10R11, (C0-C6)-alkyl-C(═N—CN)NR10R11, (C0-C6)-alkyl-NR10C(═N—NO2)NR10R11, (C0-C6)-alkyl-C(═N—NO2)NR10R11, (C0-C6)-alkyl-C(O)OR10, (C0-C6)-alkyl-C(O)NR10R11, (C0-C6)-alkyl-C(O)NR10SO2R11, C(O)NR10—(C0-C6)-alkyl-heteroaryl, C(O)NR10—(C0-C6)-alkyl-aryl, S(O)2NR10—(C0-C6)-alkyl-aryl, S(O)2NR10—(C0-C6)-alkyl-heteroaryl, S(O)2NR10-alkyl, S(O)2—(C0-C6)-alkyl-aryl, S(O)2—(C0-C6)-alkyl-heteroaryl, (C0-C6)-alkyl-C(O)—NR11—CN, O—(C0-C6)-alkyl-C(O)NR10R11, S(O)x—(C0-C6)-alkyl-C(O)OR10, S(O)x—(C0-C6)-alkyl-C(O)NR10R11, (C0-C6)-alkyl-C(O)NR10—(C0-C6)-alkyl-NR10R11, (C0-C6)-alkyl-NR10—C(O)R10, (C0-C6)-alkyl-NR10—C(O)OR10, (C0-C6)-alkyl-NR10—C(O)—NR10R11, (C0-C6)-alkyl-NR10—S(O)yNR10R11, (C0-C6)-alkyl-NR10—S(O)yR11, O—(C0-C6)-alkyl-aryl and O—(C0-C6)-alkyl-heteroaryl,
• wherein each R9 group is optionally substituted, or
• wherein each R9 group is optionally substituted by one or more R14 groups;
• R10 and R11 in each occurrence are independently selected from hydrogen, alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, and heterocycloalkyl fused heteroarylalkyl, wherein alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, and heterocycloalkyl fused heteroarylalkyl are optionally substituted one or more times, or when R10 and R11 are attached to a nitrogen atom they may be taken together to complete a 3- to 8-membered ring containing carbon atoms and optionally containing a heteroatom selected from O, S, or NR50 and which is optionally substituted one or more times;
• R14 is independently selected from hydrogen, alkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, heterocyclylalkyl and halo, wherein alkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl and heterocyclylalkyl are optionally substituted one or more times.
• R16 is selected from cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, heterocycloalkyl fused heteroarylalkyl, (i) and (ii):
• wherein cycloalkyl, heterocycloalkyl, bicycloalkyl, heterobicycloalkyl, spiroalkyl, spiroheteroalkyl, aryl, heteroaryl, cycloalkyl fused aryl, heterocycloalkyl fused aryl, cycloalkyl fused heteroaryl, heterocycloalkyl fused heteroaryl, cycloalkylalkyl, heterocycloalkylalkyl, bicycloalkylalkyl, heterobicycloalkylalkyl, spiroalkylalkyl, spiroheteroalkylalkyl, arylalkyl, heteroarylalkyl, cycloalkyl fused arylalkyl, heterocycloalkyl fused arylalkyl, cycloalkyl fused heteroarylalkyl, and heterocycloalkyl fused heteroarylalkyl are optionally substituted one or more times;
• R20 is selected from selected from hydrogen, alkyl, heteroalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, fluoroalkyl, heterocycloalkylalkyl, haloalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and aminoalkyl, wherein alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, fluoroalkyl, heterocycloalkylalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and aminoalkyl are optionally substituted one or more times, or when R20 and R21 are attached to a nitrogen atom they may be taken together to complete a 3- to 8-membered ring containing carbon atoms and optionally containing a heteroatom selected from O, S, or NR50 and which is optionally substituted one or more times;
• R21 is a monocyclic, bicyclic or tricyclic ring system wherein said bicyclic or tricyclic ring system is fused and contains at least one ring which is partially saturated and
• wherein R21 is optionally substituted one or more times, or
• wherein R21 is optionally substituted by one or more R9 groups;
• R22 is independently selected from hydrogen, halo, alkyl, cycloalkyl, hydroxy, alkoxy, aryl, heteroaryl, arylalkyl, heteroarylalkyl, alkenyl, alkynyl, NO2, NR10R11, NR10NR10R11, NR10N═CR10R11, NR10SO2R11, CN, C(O)OR11, and fluoroalkyl, wherein alkyl, cycloalkyl, alkoxy, alkenyl, alkynyl and fluoroalkyl are optionally substituted one or more times;
• R30 is selected from alkyl and (C0-C6)-alkyl-aryl, wherein alkyl and aryl are optionally substituted;
• R50 in each occurrence is independently selected from hydrogen, alkyl, aryl, heteroaryl, C(O)R80, C(O)NR80R81, SO2R80 and SO2NR80R81, wherein alkyl, aryl, and heteroaryl are optionally substituted one or more times;
• R51 is independently selected from hydrogen, alkyl, aryl, heteroaryl, arylalkyl, cycloalkylalkyl, heteroarylalkyl and haloalkyl, wherein alkyl, aryl, heteroaryl, arylalkyl, cycloalkylalkyl, heteroarylalkyl and haloalkyl are optionally substituted one or more times;
• R52 is selected from hydrogen, halo, CN, hydroxy, alkoxy, fluoroalkoxy, alkyl, aryl, heteroaryl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, haloalkyl, C(O)NR10R11 and SO2NR10R11, wherein alkoxy, fluoroalkoxy, alkyl, aryl, heteroaryl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, and haloalkyl are optionally substituted one or more times;
• R80 and R81 are independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, fluoroalkyl, heterocycloalkylalkyl, haloalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and aminoalkyl, wherein alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, fluoroalkyl, heterocycloalkylalkyl, alkenyl, alkynyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl and aminoalkyl are optionally substituted one or more times, or R80 and R81 when heterocycloalkyl, alkynyl, aryl, and heteroaryl are optionally substituted one or more times;
• R19 is independently selected from hydrogen, alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, alkynyl, aryl, heteroaryl, OH, halo, CN, C(O)NR10R11, CO2R10, OR10, OCF3, OCHF2, NR10CONR10R11, NR10COR11, NR10SO2R11, NR10SO2NR10R11, SO2NR10R11 and NR10R11, wherein alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, alkynyl, aryl, and heteroaryl are optionally substituted one or more times, or optionally two R19 groups together at one carbon atom form ═O, ═S or ═NR10;
• R25 is selected from hydrogen, alkyl, cycloalkyl, CONR10R11 and haloalkyl, wherein alkyl, cycloalkyl and haloalkyl are optionally substituted one or more times;
• L2, M2, and T2 are independently selected from CR18 and N;
• D3, G3, L3, M3, and T3 are independently selected from N, CR18, (i), and (ii),
• with the proviso that one of L3, M3, T3, D3, and G3 is (i) or (ii)
• B1 is selected from the group consisting of NR10, O and S(O)x;
• and
• Q2 is a 5- to 8-membered ring selected from cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, which is optionally substituted one or more times with R19.