Back to results
US 2020/0317588 A1Published application
18f-labeled peptide ligands useful in pet and cerenkov luminescene imaging
AssigneeCornell University
InventorJohn W. Babich
Life of this patent
Estimating the term…
Abstract
The present technology is directed to compounds, intermediates thereof, compositions thereof, medicaments thereof, and methods related to the imaging of mammalian tissue via 18F-labeled peptide ligands disclosed herein.
Claims23
A compound that is a 18F-labeled somatostatin receptor agonist according to Formula I
- or a pharmaceutically acceptable salt and/or solvate thereof, wherein
- Z10 and Z11 are each independently H or OH;
- one of W2, W3, and W4 is
- or one of Y2 and Y3 is
- and the remaining W2, W3, W4 are each independently H and the remaining Y2 and Y3 is OH or NH2;
- wherein T2 is —C(O)— or —C(O)NH—, one of R7, R8, and R9 and one of R10, R11, and R12 is
- and the remaining two of R7, R8, and R9 are each H and the remaining two of R10, R11, and R12 are each H;
- X2 is absent, 0, S, or NH;
- m′ and a′ are each independently 0, 1, 2, or 3;
- n is 0 or 1;
- p′ is 0, 1, 2, or 3, provided that when p′ is 0 then X2 is absent;
- q′ is 1 or 2;
- x′ is 0, 1, 2, or 3;
- and
- y′ is 1 or 2.
12 more elements
A compound that is a 18F-labeled somatostatin receptor agonist according to Formula II
- or a pharmaceutically acceptable salt and/or solvate thereof, wherein
- Z1 is H or OH;
- one of W5 and W6 is
- Y4 is
- and the remaining W5 and W6 are each independently H and the remaining Y4 (i.e., if not the structure indicated above) is OH or NH2;
- wherein T3 is —C(O)— or —C(O)NH—, one of R13, R14, and R15 and one of R16, R17, and R18 is
- and the remaining two of R13, R14, and R15 are each H and the remaining two of R16, R17, and R18 are each H;
- X3 is absent, 0, S, or NH;
- m″ and a″ are each independently 0, 1, 2, or 3;
- n′ is 0 or 1;
- p″ is 0, 1, 2, or 3, provided that when p″ is 0 then X3 is absent;
- q″ is 1 or 2;
- x″ is 0, 1, 2, or 3;
- and
- y″ is 1 or 2.
12 more elements
A compound that is a 18F-labeled somatostatin receptor agonist according to Formula III
- or a pharmaceutically acceptable salt and/or solvate thereof, wherein
- Z2 and Z4 are each independently H or OH;
- V is C(O)Y5 or CH2OH;
- one of W7 and W8 is
- or Y5 is
- and the remaining W7 and W8 are each independently H and the remaining Y5 (i.e., if not the structure indicated above) is OH or NH2;
- wherein
- T4 is —C(O)— or —C(O)NH—;
- one of R19, R20, and R21 and one of R22, R23, and R24 is
- and the remaining two of R19, R20, and R21 are each H and the remaining two of R22, R23, and R24 are each H;
- X4 is absent, 0, S, or NH;
- m′″ and a′″ are each independently 0, 1, 2, or 3;
- n″ is 0 or 1;
- p′″ is 0, 1, 2, or 3, provided that when p′″ is 0 then X3 is absent;
- q′″ is 1 or 2;
- x″ is 0, 1, 2, or 3;
- and
- y′″ is 1 or 2.
15 more elements
A compound that is a 18F-labeled somatostatin receptor agonist according to Formula IV
- or a pharmaceutically acceptable salt and/or solvate thereof, wherein
- Z5, Z6, and Z7 are each independently H or OH;
- one of W9 and W10 is
- and the remaining one of W9 and W10 is H, wherein
- T5 is —C(O)— or —C(O)NH—;
- one of R25, R26, and R27 is
- and the remaining two of R25, R26, and R27 are each H;
- X5 is absent, 0, S, or NH;
- m″″ is 0, 1, 2, or 3;
- n′″ is 0 or 1;
- p″″ is 0, 1, 2, or 3, provided that when p″″ is 0 then X5 is absent;
- q″″ is 1 or 2;
- x″″ is 0, 1, 2, or 3;
- and
- y″″ is 1 or 2.
12 more elements
A compound that is a 18-labeled somatostatin receptor agonist according to Formula V
- or a pharmaceutically acceptable salt and/or solvate thereof, wherein
- Z8 and Z9 are each independently H or OH;
- one of W11 and W12 is
- or Y6 is
- and the remaining W11 and W12 are each independently H and the remaining Y6 (i.e., if not the structure indicated above) is OH or NH2;
- wherein
- T6 is —C(O)— or —C(O)NH—;
- one of R28, R29, and R30 and one of R11, R32, and R33 is
- and the remaining two of R28, R29, and R30 are each H and the remaining two of R31, R32, and R33 are each H;
- X6 is absent, 0, S, or NH;
- m′″″ and a″″ are each independently 0, 1, 2, or 3;
- n″″ is 0 or 1;
- p′″″ is 0, 1, 2, or 3, provided that when p′″″ is 0 then X6 is absent;
- q′″″ is 1 or 2;
- x′″″ is 0, 1, 2, or 3;
- and
- y′″″ is 1 or 2.
14 more elements
A compound that is a 18F-labeled bombesin receptor agonist of Formula VI or Formula VIA
- or a pharmaceutically acceptable salt and/or solvate thereof,
- where independently in each of Formulas VI and VIA one of W13 and W14 is
- or one of Y7, Y8, Y9, and Y10 is
- and the remaining W13 and W14 are each independently H and the remaining Y7, Y8, Y9, and Y10 (i.e., if not the structure indicated above) is OH or NH2;
- wherein
- T7 is —C(O)— or —C(O)NH—;
- one of R28, R29, and R30 and one of R31, R32, and R33 is
- and the remaining two of R28, R29, and R30 are each H and the remaining two of R31, R32, and R33 are each H;
- X6 is absent, 0, S, or NH;
- b and e are each independently 0, 1, 2, or 3;
- f is 0, 1, 2, or 3, provided that when f is 0 then X7 is absent;
- g is 1 or 2;
- c is 0, 1, 2, or 3;
- and
- d is 1 or 2.
12 more elements
A 18F-labeled seprase binding compound comprising
- a seprase binding compound comprising a primary amine, secondary amine, NH2 of a guanadinyl group, or NH2 of an amidinyl group covalently bonded to W15 or a carboxylic acid or amide of the seprase binding compound that is modified to a —C(O)Y11 group, wherein
- W15 is
- Y11 is
- T8 is —C(O)— or —C(O)NH—;
- one of R34, R35, and R36 and one of R37, R38, and R39 is
- and the remaining two of R40, R41, and R42 are each H and the remaining two of R43, R44, and R45 are each H;
- X8 is absent, O, S, or NH;
- b′ and e′ are each independently 0, 1, 2, or 3;
- f′ is 0, 1, 2, or 3, provided that when f′ is 0 then X8 is absent;
- g′ is 1 or 2;
- c′ is 0, 1, 2, or 3;
- and
- d′ is 1 or 2.
10 more elements
-18. (canceled)
A method comprising modifying a peptide ligand to provide a 18F-labeled peptide ligand, wherein the modifying comprises one or both of
- covalently bonding a primary amine, secondary amine, NH2 of a guanadinyl group, or NH2 of an amidinyl group of the peptide ligand to W1;
- or
- converting a carboxylic acid or amide of the peptide ligand to a —C(O)Y1 group;
- wherein
- W1 is
- Y1 is
- T1 is —C(O)— or —C(O)NH—,
- one of R1, R2, and R3 and one of R4, R5, and R6 is
- and the remaining two of R1, R2, and R3 are each H and the remaining two of R4, R5, and R6 are each H;
- X1 is absent, O, S, or NH;
- m and a are each independently 0, 1, 2, or 3;
- n is 1 or 2;
- p is 0, 1, 2, or 3, provided that when p is 0 then X1 is absent;
- q is 1 or 2;
- x is 0, 1, 2, or 3;
- and
- y is 1 or 2.
14 more elements
A method of obtaining an image, the method comprising
- administering an effective amount of a 18F-labeled peptide ligand to a subject, wherein the 18F-labeled peptide ligand comprises a somatostatin receptor agonist, a bombesin receptor agonist, or a seprase binding compound;
- and
- subsequent to the administering, detecting one or more of positron emission, gamma rays from positron emission and annihilation, and Cerenkov radiation due to positron emission.
-23. (canceled)
Dependencies are inferred from the claim text.