Compounds and methods for amine oxidase imaging

1 . A compound according to Formula I

wherein

a and b are independently an integer from 0 to 10;

A is a structure selected from the group consisting of

R 3 and R 4 are independently selected from the group consisting of

NHR 9′ , —OR 9′ , SR 9′ ,

linear or branched, substituted or non-substituted (C 1-10 )alkyl, (C 2-10 )alkenyl and (C 2-10 )alkynyl, or substituted or non-substituted carbocycle selected from the group consisting of (C 3-10 )carbocycle;

substituted or non-substituted triphenylphosphine connected via the phosphorous;

N-maleimidyl; and

halogens, or one of R 3 or R 4 is a proteinogenic amino acid, a non-proteinogenic amino acid or a peptide, and the other of R 3 or R 4 is a halogen;

L is absent or a linker;

X, Y and Z are independently selected from the group consisting of O, N and S;

R 9′ is selected from the group consisting of

hydrogen;

linear or branched, substituted or non-substituted, optionally sulfonated, (C 1-10 )alkyl, (C 2-10 )alkenyl, or (C 2-10 )alkynyl;

linear or branched, substituted or non-substituted (C 1-20 )alkyl ether, (C 2-10 )alkenyl ether, (C 2-10 )alkynyl ether, or (C 4-10 )carbocyclic ether;

substituted or non-substituted carbocycle selected from the group consisting of (C 3-10 )carbocycle;

substituted or non-substituted triphenylphosphine connected via the phosphorous;

substituted or non-substituted (C 3-6 )heterocycle and (C 7 -C 10 )carbo- or hetero-bicycle having 1 to 3 heteroatoms each independently selected from N, O and S;

a proteinogenic amino acid or non-proteinogenic amino acid;

a peptide or a peptide comprising 1 to 2000 amino acids;

a collagen peptide, fibronectin peptide, fibrillin peptide, elastin peptide, or an RGD (arginylglycylaspartic acid) peptide; and

an antibody;

R 9 is selected from residues defined for R 9′ and is further selected from the group consisting of

azide, N-maleimidyl, —NH 2 , —OH and —SH 2 ;

R 9″ is selected from the group consisting of

halogen, substituted or non-substituted triphenylphosphine connected via the phosphorous, azide, —SR 10 ,

R 10 is selected from the group consisting of

linear or branched, substituted or non-substituted (C 1-10 )alkyl, (C 2-10 )alkenyl, or (C 2-10 )alkynyl; and

linear or branched, substituted or non-substituted (C 1-20 )alkyl ether, (C 2-10 )alkenyl ether, (C 2-10 )alkynyl ether, or (C 4-10 )carbocyclic ether;

R 5 is selected from the group consisting of

hydrogen or —OH; and

halogens;

R 6 and R 8 are independently selected from the group consisting of hydrogen, —OH, and halogen; and

R 7 is each independently selected from the group consisting of

hydrogen;

linear or branched, substituted or non-substituted (C 1-10 )alkyl, (C 2-10 ) alkenyl, or (C 2-10 )alkynyl;

linear or branched, substituted or non-substituted (C 1-20 )alkyl ether, (C 2-10 )alkenyl ether, (C 2-10 )alkynyl ether, or (C 4-10 )carbocyclic ether;

—N 2 forming an azide with the nitrogen atom of A; and

tert-Butyloxycarbonyl (Boc), 9-fluorenylmethoxycarbonyl (Fmoc), benzyloxycarbonyl(Cbz), acetyl (Ac), trifluoroacetic acid (TFA), phthalimide, benzyl (Bn), triphenylmethyl (Tr), benzylidene, or para-toluenesulfonyl (Ts);

and salts and solvates thereof.

2 . The compound according to claim 1 , wherein

a and b are independently an integer from 0 to 3;

A is a structure selected from the group consisting of

R 3 and R 4 are independently selected from the group consisting of

—NHR 9′ , —OR 9′ , SR 9′ ,

linear or branched, substituted or non-substituted (C 1-10 )alkyl;

triphenylphosphine connected via the phosphorous;

N-maleimidyl; and

halogen or one of R 3 or R 4 is a proteinogenic amino acid, a non-proteinogenic amino acid or a peptide, and the other of R 3 or R 4 is a halogen;

L is absent or a linker selected from the group consisting of

linear or branched, substituted or non-substituted (C 1-10 )alkyl;

wherein c and d are independently selected from 1, 2, 3, 4, and 5; and

linear or branched, substituted or non-substituted (C 1-20 )alkyl ether;

X, Y and Z are independently selected from the group consisting of O, N and S;

R 9′ is selected from the group consisting of

hydrogen;

linear or branched, substituted or non-substituted, optionally sulfonated, (C 1-10 )alkyl, (C 2-10 )alkenyl, or (C 2-10 )alkynyl;

linear or branched, substituted or non-substituted (C 1-20 )alkyl ether;

triphenylphosphine connected via the phosphorous;

a proteinogenic amino acid or a non-proteinogenic amino acid;

a peptide or a peptide comprising 1 to 2000 amino acids;

a collagen peptide, fibronectin peptide, fibrillin peptide, elastin peptide, or an RGD (arginylglycylaspartic acid) peptide; and

an antibody;

R 9 is selected from residues defined for R 9′ and is further selected from the group consisting of

azide, N-maleimidyl, —NH 2 , —OH and —SH 2 ;

R 9″ is selected from the group consisting of

azide, —SR 10 ,

R 10 is selected from the group consisting of

linear or branched, substituted or non-substituted (C 1-10 )alkyl; and

linear or branched, substituted or non-substituted (C 1-20 )alkyl ether;

R 5 is selected from the group consisting of

hydrogen or —OH; and

halogen;

R 6 and R 8 are independently selected from the group consisting of hydrogen and halogen; and

R 7 is each independently selected from the group consisting of

hydrogen;

linear or branched, substituted or non-substituted (C 1-10 )alkyl;

linear or branched, substituted or non-substituted (C 1-20 )alkyl ether;

—N 2 forming an azide with the nitrogen atom of A; and

Boc, Fmoc, Cbz, Ac, TFA, phthalimide, Bn, Tr, benzylidene, or Ts.

3 . The compound according to claim 1 , wherein

a is an integer from 0 to 3;

b is 0;

A is a structure selected from the group consisting of

R 3 is

R 4 is hydrogen, linear or branched, substituted or non-substituted (C 1-10 )alkyl;

L is absent or a linker selected from the group consisting of

linear or branched, substituted or non-substituted (C 1-10 )alkyl;

wherein c and d are independently selected from 1, 2, 3, 4, and 5; and

linear or branched, substituted or non-substituted (C 1-10 )alkyl ether;

X is selected from the group consisting of O, N and S;

Z is O;

R 9 is selected from the group consisting of

hydrogen or N-maleimidyl;

linear or branched, substituted or non-substituted (C 1-10 )alkyl, (C 2-10 )alkenyl, or (C 2-10 )alkynyl;

linear or branched, substituted or non-substituted (C 1-20 )alkyl ether;

triphenylphosphine connected via the phosphorous:

a proteinogenic amino acid, a non-proteinogenic amino acid, lysine, proline, glycine, 4-hydroxyproline, 4-aminoproline, or 4-aminooxyproline;

a peptide or a peptide comprising 1 to 2000 amino acids;

a collagen peptide, fibronectin peptide, fibrillin peptide, elastin peptide, or an RGD (arginylglycylaspartic acid) peptide;

an antibody an anti-collagen, anti-elastin, anti-fibronectin, or anti-fibrillin antibody; and

azide, —NH 2 , —OH, or —SH 2 ;

R 9″ is selected from the group consisting of

azide, —SR 10 ,

R 10 is selected from the group consisting of linear or branched, substituted or non-substituted (C 1-10 )alkyl, (C 2-10 )alkenyl, and (C 2-10 ) )alkynyl;

R 5 is selected from the group consisting of

hydrogen or —OH; and

halogen;

R 6 and R 8 are independently selected from the group consisting of hydrogen and halogen; and

R 7 is each independently selected from the group consisting of

hydrogen;

linear or branched, substituted or non-substituted (C 1-10 )alkyl;

—N 2 forming an azide with the nitrogen atom of A; and

Boc, Fmoc, or Cbz.

4 . The compound according to claim 1 , wherein the compound is a compound according to Formula II

wherein

a is 1 or 2;

b is 0;

A is a structure selected from the group consisting of

R 3 is

R 4 is hydrogen or linear or branched, substituted or non-substituted (C 1-10 )alkyl;

L is absent,

wherein c and d are independently selected from 1, 2, 3, 4, and 5;

X is selected from the group consisting of O and N;

Z is O;

R 9 is selected from the group consisting of

hydrogen or N-maleimidyl;

linear or branched, substituted or non-substituted (C 1-10 )alkyl;

triphenylphosphine connected via the phosphorous;

a proteinogenic amino acid, a non-proteinogenic amino acid, lysine, proline, glycine, 4-hydroxyproline, 4-aminoproline, or 4-aminooxyproline;

a collagen peptide, fibronectin peptide, fibrillin peptide, elastin peptide, or an RGD (arginylglycylaspartic acid) peptide; and

azide, —NH 2 , —OH and —SH 2 ;

R 9″ is selected from the group consisting of

azide,

and

R 7 is each independently selected from the group consisting of

hydrogen; and

linear or branched, substituted or non-substituted (C 1-10 )alkyl.

5 . The compound according to claim 1 , wherein the linear or branched, substituted or non-substituted (C 1-10 )alkyl for at least one of R 3 , R 4 , R 7 , R 9′ and/or R 10 is selected from methyl, ethyl, and propyl.

6 . The compound according to claim 1 , wherein the (C 3-10 )carbocycle for at least one of R 3 , R 4 and/or R 9′ is an aromatic (C 6 )carbocycle.

7 . The compound according to claim 1 , wherein R 3 and/or R 4 are an aromatic (C 6 )carbocycle if a and/or b are 0.

8 . The compound according to claim 1 , wherein for at least one of R 3 , R 4 , R 5 , R 6 , R 8 and/or R 9″ the halogen is selected from F, Cl, Br, and I.

9 . The compound according to claim 1 , wherein if one of R 3 or R 4 is a proteinogenic amino acid, a non-proteinogenic amino acid, or a peptide, the other of R 3 or R 4 is a halogen.

10 . The compound according to claim 1 , wherein the linker is selected from the group consisting of:

linear or branched, substituted or non-substituted (C 1-10 )alkyl, (C 2-10 )alkenyl, or (C 2-10 )alkynyl;

a (C 1-10 ) alkyl comprising one or more amide functionalities in the alkyl chain;

wherein c and d are independently selected from 1, 2, 3, 4, and 5; and

linear or branched, substituted or non-substituted (C 1-20 )alkyl ether, (C 2-10 )alkenyl ether, (C 2-10 )alkynyl ether, and (C 4-10 )carbocyclic ether.

11 . The compound according to claim 1 , wherein Z is selected from the group consisting of O and N.

12 . The compound according to claim 1 , wherein for at least one of R 7 , R 9 and/or R 10 , the (C 1-20 )alkyl ether is a polyethylene glycol (PEG) chain or a PEG chain with 1 to 10 ethylene oxide entities.

13 . The compound according to claim 1 , wherein for R 9′ , the (C 3-10 )carbocycle is a carbocycle substituted by a substituent selected from the group consisting of Cl, F, Br, substituted or non-substituted methyl, —(CF 3 ), ethyl, propyl and cyclopropyl.

14 . The compound according to claim 1 , wherein for R 9′ , the (C 7 -C 10 )heterobicycle is a substituted or non-substituted (C 7 )heterobicycle having 2 heteroatoms selected from N and S.

15 . The compound according to claim 1 , wherein for R 9′ , the proteinogenic amino acid or non-proteinogenic amino acid is an aminooxy or hydrazide derivative of the proteinogenic or non-proteinogenic amino acid.

16 . The compound according to claim 1 , wherein for R 9′ , the proteinogenic amino acid or non-proteinogenic amino acid is selected from the group consisting of lysine, proline, glycine, 4-hydroxyproline, 4-aminoproline, and 4-aminooxyproline.

17 . The compound according to claim 1 , wherein for R 9′ , the peptide comprises 1 to 2000 amino acids.

18 . The compound according to claim 1 , wherein for R 9′ , the peptide comprises 1 to 10, [proline]-[4-hydroxyproline]-[glycine] units.

19 . The compound according to claim 1 , wherein for R 9′ , the antibody is an anti-collagen, anti-elastin, anti-fibronectin or anti-fibrillin antibody.