Lox enzyme inhibiting methods and compositions
AssigneeAnovia Biosciences, Inc.
InventorsMichael Clare, Juan Du, Xiang Li, Ronggang Liu
Life of this patent
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Abstract
This invention relates to compounds, pharmaceutical compositions and their use for treating fibrotic disorders, proliferative disorders, cardiovascular diseases, acute and chronic inflammatory disorders, primary and metastatic cancer, pulmonary conditions, ocular diseases, or neurological and neuropsychiatric conditions. One particular aspect of the inventions relates to inhibitors of the family of lysyl oxidase enzymes and their use as therapeutics for fibrotic disorders. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
Claims31
A LOX enzyme-inhibiting compound in accordance with Formula I or Formula II, or a pharmaceutically acceptable salt or hydrate thereof:
- wherein:
- X is independently selected from —OR1, —SO2R1, and —C(═O)R′;
- Y is independently selected from —SO2R2 and —C(═O)R2;
- Z is independently selected from —R3, —CH2—R3, —SO2R3, —C(═O)R3, and —OR3;
- R1 is phenyl or heteroaryl containing 1 to 2 heteroatom(s) each independently selected from N, O, and S, wherein said phenyl or heteroaryl is substituted with-CR4R5NH2, and optionally, halogen or lower alkyl, where R4 and R5 are independently H or lower alkyl or R4 and R5 form a (C1-C8) cycloalkyl or (C1-C8) hetero-cycloalkyl;
- R2 is substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, substituted or unsubstituted heteroaryl containing 1 to 2 heteroatom(s) each independently selected from N, O, and S, (C1-C8) alkyl, (C1-C8) cycloalkyl, mono-, di-, or trihalo(C1-C4)alkyl, or —NR6R7, where R6 and R7 are independently selected from H and lower alkyl or where R6 and R7 form together a (C3-C6) hetero-cycloalkyl, wherein the (C3-C6) hetero-cycloalkyl optionally contains besides the nitrogen one additional heteroatom selected from N, O, and S, wherein N is optionally substituted with lower alkyl, —SO2R8, or —OR8, and wherein S is unsubstituted or forms sulfonyl, wherein said substituted phenyl, benzyl, or heteroaryl has at least one substituent being halogen, mono-, di-, or trihalo(C1-C4)alkyl, —SO2R8, or —OR′, where R8 is lower alkyl, cyano, lower alkyl, or —SO2NR9R10, and where R9 and R10 are independently selected from H and lower alkyl;
- R3 is unsubstituted or substituted phenyl, substituted or unsubstituted benzyl, substituted or unsubstituted heteroaryl containing 1 to 2 heteroatom(s) each independently selected from N, O, and S, mono-, di-, or trihalo(C1-C4)alkyl, (C1-C8) cycloalkyl, (C1-C8) alkyl, or —NR11R12, where R11 and R12 are independently selected from H and lower alkyl or where R11 and R12 form together a (C3-C6) hetero-cycloalkyl, wherein the (C3-C6) hetero-cycloalkyl optionally contains besides the nitrogen one additional heteroatom selected from N, O, and S, wherein N is optionally substituted with lower alkyl, —SO2R13, or —OR13, and wherein S is unsubstituted or forms sulfonyl, wherein said substituted phenyl, benzyl, or heteroaryl has at least one substituent being halogen, mono-, di-, or trihalo(C1-C4)alkyl, —SO2R14, or —OR14, where R14 is lower alkyl, cyano, lower alkyl, or —SO2NR15R16, and where R15 and R16 are independently selected from H and lower alkyl,
- or a tautomer or stereoisomer thereof.
2-13. (canceled)
(canceled)
17-18. (canceled)
22-38. (canceled)
The compound according to claim 0, wherein the compound has a structure represented by a formula:
41-43. (canceled)
The compound according to claim 0, wherein the compound has a structure represented by a formula:
45-46. (canceled)
The compound according to claim 0, wherein the compound has a structure represented by a formula:
48-50. (canceled)
The compound according to claim 0, wherein the compound has a structure represented by a formula:
52-54. (canceled)
The compound according to claim 0, wherein the compound is selected from:
- or a pharmaceutically acceptable salt thereof.
The compound according to claim 0, wherein the compound has a structure represented by a formula:
57-59. (canceled)
The compound according to claim 0, wherein the compound has a structure represented by a formula:
61-63. (canceled)
65-75. (canceled)
The compound according to claim 2, wherein X is independently selected from —OR1 and —SO2R1, wherein R1 is phenyl, wherein said phenyl is substituted with —CR4R5NH2, and optionally, halogen or lower alkyl, and wherein R4 and R5 are independently H or lower alkyl or R4 and R5 form a cycloalkyl or hetero-cycloalkyl.
Dependencies are inferred from the claim text.