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US 2013/0158063 A1Published application
Compounds, Compositions and Methods Related to PPAR Antagonists
AssigneeGeorgetown University
InventorsMilton Lang Brown, Yali Kong, Yong Liu, Robert Glazer, York Tomita
Life of this patent
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Abstract
Disclosed are compounds, compositions and methods related PPAR antagonists. Certain compounds are effective at inhibiting PPARs. The compositions can be used to inhibit PPARs, treat cancer and treat metabolic disorders.
Claims27
A compound having the structure of:
- wherein:
- A is:
- X is absent or present, if present X is —NH—;
- Y is C or N, if N R5 is absent;
- R1, R2, R3, R4 and R5 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl, cyano or nitro, wherein at least one of R1, R2, R3, R4 and R5 is not hydrogen;
- B is:
- R6, R7 and R8 are independently hydrogen, —C(O)—CH2—R22 or
- R16 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R17, R18, R19, R20 and R21 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R17, R18, R19, R20 and R21 is not hydrogen,
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, wherein pyridine is substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro,
- R22 is hydroxyl, halo, or hydrogen, wherein at least one of R6, R7 and R8 is not hydrogen;
- Z is absent or present, if present Z is —N(H)—;
- R9 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—;
- R10 and R11 are independently hydrogen or
- R16 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R17, R18, R19, R20 and R21 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R17, R18, R19, R20 and R21 is not hydrogen, wherein R10 and R11 are not both hydrogen,
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro;
- R23 is hydrogen or
- R16 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R17, R18, R19, R20 and R21 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R17, R18, R19, R20 and R21 is not hydrogen
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro,
- R12, R13, R14 and R15 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R12, R13, R14 and R15 is not hydrogen;
- R24 is —CH2—, —CH2CH2—, —CH2CH2CH2— or —CH2CH2CH2CH2—;
- and
- R25 is
- R26, R27, R28, R29 and R30 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R26, R27, R28, R29 and R30 is not hydrogen,
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro;
- and
- wherein the compound is not
43 more elements
2-14. (canceled)
A compound having the structure of:
- wherein:
- L is —C(O)CHCH—, —C(O)(CH2)1-3—, —C(O)(CHCH)2—, —(CHCH)1-2 or —(CH2)1-4—;
- R31, R32, R33, R34, R35, R36, R37, R38, R39 or R40 is independently hydrogen, —B(OH)2, C1-C3 alkyl, C1-C3 i alkoxy, halo, C1-C3 haloalkyl, cyano or nitro, wherein at least four of R31, R32, R33, R34, R35, R36, R32, R38, R39 or R40 are not hydrogen.
17-20. (canceled)
A compound having the structure of:
- wherein:
- R41 is hydrogen, hydroxyl, halo, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, nitro, cyano or —B(OH)2;
- R42 is hydrogen hydroxyl, halo, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, nitro, cyano, —B(OH)2 or —C(O)—R43,
- R43 is C1-C3 alkyl;
- and
- wherein R41 and R42 are not both hydrogen and wherein R41 is not hydrogen if R42 is cyano.
3 more elements
A method of inhibiting peroxisome proliferator-activated receptors (PPAR) comprising administering a composition comprising a compound having the structure:
- or a pharmaceutically acceptable salt, prodrug, clathrate, tautomer or solvate thereof, wherein:
- A is:
- X is absent or present, if present X is —NH—;
- Y is C or N, if N R5 is absent;
- R1, R2, R3, R4 and R5 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl, cyano or nitro, wherein at least one of R1, R2, R3, R4 and R5 is not hydrogen;
- B is:
- R6, R7 and R8 are independently hydrogen, —C(O)—CH2—R22 or
- R16 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R17, R18, R19, R20 and R21 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R17, R18, R19, R20 and R21 is not hydrogen,
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, wherein pyridine is substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro,
- R22 is hydroxyl, halo, or hydrogen, wherein at least one of R6, R7 and R8 is not hydrogen;
- Z is absent or present, if present Z is —N(H)—;
- R9 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—;
- R10 and R11 are independently hydrogen or
- R16 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R17, R18, R19, R20 and R21 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R17, R18, R19, R20 and R21 is not hydrogen, wherein R10 and R11 are not both hydrogen,
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro;
- R23 is hydrogen or
- R16 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R17, R18, R19, R20 and R21 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R17, R18, R19, R20 and R21 is not hydrogen
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro,
- R12, R13, R14 and R15 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R12, R13, R14 and R15 is not hydrogen;
- R24 is —CH2—, —CH2CH2—, —CH2CH2CH2— or —CH2CH2CH2CH2—;
- and
- R25 is
- R26, R27, R28, R29 and R30 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R26, R27, R28, R29 and R30 is not hydrogen,
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro;
- R51 is a 5 membered heterocyclic structure having two substituents selected from ═O and ═S,
- R52 is phenyl, ethyl, butyl, cyclohexyl, biphenyl, phenoxybenzyl propyl 1-methylcyclopropanecarboxylate or halogenated benzene,
- R53 is O, S or NH,
- R56 is CH and R57 is CH, R56 is N and R57 is CH, or R56 is CH and R57 is N,
- R54 is —SO2—, —NH—, —S(O)2NH—, —NHCH2—, —NHCH2CH2—, —NHCH2CH2CH2—, —NHCOO—, —SO2NHCOO— or —SO2NHC(O)—,
- R55 is H, C1-C3 alkyl, heteroaryl, heterocyclyl, aryl or cycloalkyl;
- L is —C(O)CHCH—, —C(O)(CH2)1-3—, —C(O)(CHCH)2—, —(CHCH)1-2 or —(CH2)1-4—;
- R31, R32, R33, R34, R35, R36, R37, R38, R39 or R40 is independently hydrogen, —B(OH)2, C1-C3 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl, cyano or nitro, wherein at least four of R31, R32, R33, R34, R35, R36, R37, R38, R39 or R40 are not hydrogen;
- R41 is hydrogen, hydroxyl, halo, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, nitro, cyano or —B(OH)2;
- R42 is hydrogen hydroxyl, halo, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, nitro, cyano, —B(OH)2 or —C(O)—R43, and
- R43 is C1-C3 alkyl.
52 more elements
24-40. (canceled)
A method of treating cancer comprising administering a composition comprising a compound having the structure:
- or a pharmaceutically acceptable salt, prodrug, clathrate, tautomer or solvate thereof, wherein:
- A is:
- X is absent or present, if present X is —NH—;
- Y is C or N, if N R5 is absent;
- R1, R2, R3, R4 and R5 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl, cyano or nitro, wherein at least one of R1, R2, R3, R4 and R5 is not hydrogen;
- B is:
- R6, R7 and R8 are independently hydrogen, —C(O)—CH2—R22 or
- R16 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R17, R18, R19, R20 and R21 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R17, R18, R19, R20 and R21 is not hydrogen,
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, wherein pyridine is substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro,
- R22 is hydroxyl, halo, or hydrogen, wherein at least one of R6, R7 and R8 is not hydrogen;
- Z is absent or present, if present Z is —N(H)—;
- R9 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—;
- R10 and R11 are independently hydrogen or
- R16 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R17, R18, R19, R20 and R21 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R17, R18, R19, R20 and R21 is not hydrogen, wherein R10 and R11 are not both hydrogen,
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro;
- R23 is hydrogen or
- R16 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R17, R18, R19, R20 and R21 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R17, R18, R19, R20 and R21 is not hydrogen
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro,
- R12, R13, R14 and R15 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R12, R13, R14 and R15 is not hydrogen;
- R24 is —CH2—, —CH2CH2—, —CH2CH2CH2— or —CH2CH2CH2CH2—;
- and
- R25 is
- R26, R27, R28, R29 and R30 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R26, R27, R28, R29 and R30 is not hydrogen,
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro;
- R51 is a 5 membered heterocyclic structure having two substituents selected from ═O and ═S,
- R52 is phenyl, ethyl, butyl, cyclohexyl, biphenyl, phenoxybenzyl propyl 1-methylcyclopropanecarboxylate or halogenated benzene,
- R53 is O, S or NH,
- R56 is CH and R57 is CH, R56 is N and R57 is CH, or R56 is CH and R57 is N,
- R54 is —SO2—, —NH—, —S(O)2NH—, —NHCH2—, —NHCH2CH2—, —NHCH2CH2CH2—, —NHCOO—, —SO2NHCOO— or —SO2NHC(O)—,
- R55 is H, C1-C3 alkyl, heteroaryl, heterocyclyl, aryl or cycloalkyl;
- L is —C(O)CHCH—, —C(O)(CH2)1-3—, —C(O)(CHCH)2—, —(CHCH)1-2 or —(CH2)1-4—;
- R31, R32, R33, R34, R35, R36, R37, R38, R39 or R40 is independently hydrogen, —B(OH)2, C1-C3 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl, cyano or nitro, wherein at least four of R31, R32, R33, R34, R35, R36, R37, R38, R39 or R40 are not hydrogen;
- R41 is hydrogen, hydroxyl, halo, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, nitro, cyano or —B(OH)2;
- R42 is hydrogen hydroxyl, halo, C13-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, nitro, cyano, —B(OH)2 or —C(O)—R43, and
- R43 is C1-C3 alkyl.
52 more elements
A method of treating metabolic disorders comprising administering a composition comprising a compound having the structure:
- or a pharmaceutically acceptable salt, prodrug, clathrate, tautomer or solvate thereof, wherein:
- A is:
- X is absent or present, if present X is —NH—;
- Y is C or N, if N R5 is absent;
- R1, R2, R3, R4 and R5 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl, cyano or nitro, wherein at least one of R1, R2, R3, R4 and R5 is not hydrogen;
- B is:
- R6, R7 and R8 are independently hydrogen, —C(O)—CH2—R22 or
- R16 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R17, R18, R19, R20 and R21 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R17, R18, R19, R20 and R21 is not hydrogen,
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, wherein pyridine is substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro,
- R22 is hydroxyl, halo, or hydrogen, wherein at least one of R6, R7 and R8 is not hydrogen;
- Z is absent or present, if present Z is —N(H)—;
- R9 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—;
- R10 and R11 are independently hydrogen or
- R16 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R17, R18, R19, R20 and R21 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R17, R18, R19, R20 and R21 is not hydrogen, wherein R10 and R11 are not both hydrogen,
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro;
- R23 is hydrogen or
- R16 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R17, R18, R19, R20 and R21 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R17, R18, R19, R20 and R21 is not hydrogen
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro,
- R12, R13, R14 and R15 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R12, R13, R14 and R15 is not hydrogen;
- R24 is —CH2—, —CH2CH2—, —CH2CH2CH2— or —CH2CH2CH2CH2—;
- and
- R25 is
- R26, R27, R28, R29 and R30 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R26, R27, R28, R29 and R30 is not hydrogen,
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro;
- R51 is a 5 membered heterocyclic structure having two substituents selected from ═O and ═S,
- R52 is phenyl, ethyl, butyl, cyclohexyl, biphenyl, phenoxybenzyl propyl 1-methylcyclopropanecarboxylate or halogenated benzene,
- R53 is O, S or NH,
- R56 is CH and R57 is CH, R56 is N and R57 is CH, or R56 is CH and R57 is N,
- R54 is —SO2—, —NH—, —S(O)2NH—, —NHCH2—, —NHCH2CH2—, —NHCH2CH2CH2—, —NHCOO—, —SO2NHCOO— or —SO2NHC(O)—,
- R55 is H, C1-C3 alkyl, heteroaryl, heterocyclyl, aryl or cycloalkyl;
- L is —C(O)CHCH—, —C(O)(CH2)1-3—, —C(O)(CHCH)2—, —(CHCH)1-2 or —(CH2)1-4—;
- R31, R32, R33, R34, R35, R36, R37, R38, R39 or R40 is independently hydrogen, —B(OH)2, C1-C3 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl, cyano or nitro, wherein at least four of R31, R32, R33, R34, R35, R36, R37, R38, R39 or R40 are not hydrogen;
- R41 is hydrogen, hydroxyl, halo, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, nitro, cyano or —B(OH)2;
- R42 is hydrogen hydroxyl, halo, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, nitro, cyano, —B(OH)2 or —C(O)—R43, and
- R43 is C1-C3 alkyl.
52 more elements
A method of preventing or treating a PPAR-mediated disease or condition comprising administering a therapeutically effective amount of a composition comprising a compound having the structure:
- or a pharmaceutically acceptable salt, prodrug, clathrate, tautomer or solvate thereof, wherein:
- A is:
- X is absent or present, if present X is —NH—;
- Y is C or N, if N R5 is absent;
- R1, R2, R3, R4 and R5 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl, cyano or nitro, wherein at least one of R1, R2, R3, R4 and R5 is not hydrogen;
- B is:
- R6, R7 and R8 are independently hydrogen, —C(O)—CH2—R22 or
- R16 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R17, R18, R19, R20 and R21 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R17, R18, R19, R20 and R21 is not hydrogen,
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, wherein pyridine is substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro,
- R22 is hydroxyl, halo, or hydrogen, wherein at least one of R6, R7 and R8 is not hydrogen;
- Z is absent or present, if present Z is —N(H)—;
- R9 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—;
- R10 and R11 are independently hydrogen or
- R16 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R17, R18, R19, R20 and R21 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R17, R18, R19, R20 and R21 is not hydrogen, wherein R10 and R11 are not both hydrogen,
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro;
- R23 is hydrogen or
- R16 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R17, R18, R19, R20 and R21 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R17, R18, R19, R20 and R21 is not hydrogen
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro,
- R12, R13, R14 and R15 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R12, R13, R14 and R15 is not hydrogen;
- R24 is —CH2—, —CH2CH2—, —CH2CH2CH2— or —CH2CH2CH2CH2—;
- and
- R25 is
- R26, R27, R28, R29 and R30 are independently hydrogen, C1-C3 alkyl, C4-C6 alkyl, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro, wherein at least one of R26, R27, R28, R29 and R30 is not hydrogen,
- R50 is H or C1-C6 alkyl,
- R44 is —CH2—, —CH2CH2—, —CH2CH2C(O)—, —CH2C(O)—, or —C(O)—,
- R45 is substituted pyridine, substituted with C1-C6 alkyl, hydrogen, C1-C3 alkoxy, halo, C1-C3 haloalkyl,
- cyano or nitro;
- R51 is a 5 membered heterocyclic structure having two substituents selected from ═O and ═S,
- R52 is phenyl, ethyl, butyl, cyclohexyl, biphenyl, phenoxybenzyl propyl 1-methylcyclopropanecarboxylate or halogenated benzene,
- R53 is O, S or NH,
- R56 is CH and R57 is CH, R56 is N and R57 is CH, or R56 is CH and R57 is N,
- R54 is —SO2—, —NH—, —S(O)2NH—, —NHCH2—, —NHCH2CH2—, —NHCH2CH2CH2—, —NHCOO—, —SO2NHCOO— or —SO2NHC(O)—,
- R55 is H, C1-C3 alkyl, heteroaryl, heterocyclyl, aryl or cycloalkyl;
- L is —C(O)CHCH—, —C(O)(CH2)1-3—, —C(O)(CHCH)2—, —(CHCH)1-2 or —(CH2)1-4—;
- R31, R32, R33, R34, R35, R36, R37, R38, R39 or R40 is independently hydrogen, —B(OH)2, C1-C3 alkyl, C1-C3 i alkoxy, halo, C1-C3 haloalkyl, cyano or nitro, wherein at least four of R31, R32, R33, R34, R35, R36, R37, R38, R39 or R40 are not hydrogen;
- R41 is hydrogen, hydroxyl, halo, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, nitro, cyano or —B(OH)2;
- R42 is hydrogen hydroxyl, halo, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, nitro, cyano, —B(OH)2 or —C(O)—R43, and
- R43 is C1-C3 alkyl.
52 more elements
(canceled)
A compound having the structure of:
- wherein:
- R51 is 5 membered heterocyclic structure having two substituents selected from ═O and ═S,
- R52 is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, 1-methylcyclopropanecarboxylate C1-C6 alkyl,
- C1-C3 alkoxy, halo, C1-C3 haloalkyl, cyano or nitro,
- R50 is C1-C6 alkyl,
- R53 is O, S or NH,
- R56 is CH and R57 is CH, R56 is N and R57 is CH, or R56 is CH and R57 is N,
- R54 is —SO2—, —NH—, —S(O)2NH—, —NHCH2—, —NHCH2CH2—, —NHCH2CH2CH2—, —NHCOO—, —SO2NHCOO— or —SO2NHC(O)—,
- R55 is H, C1-C3 alkyl, heteroaryl, heterocyclyl, aryl or cycloalkyl.
6 more elements
Dependencies are inferred from the claim text.