PSMA binding ligand-linker conjugates and methods for using
Described herein are prostate specific membrane antigen (PSMA) binding conjugates that are useful for delivering therapeutic, diagnostic and imaging agents. Also described herein are pharmaceutical composition containing them and methods of using the conjugates and compositions. Also described are processes for manufacture of the conjugates and the compositions containing them.
1. A compound of the formula:
B-L-D
or a salt thereof, wherein
B is a ligand of prostate specific membrane antigen comprising a urea of two amino acids;
L comprises an aminocaproic acid divalent radical, wherein L has a molecular weight of less than about 300 g/mol;
L is covalently bound to D via an amide bond; and
D is a drug.
2. The compound of claim 1 or a salt thereof, wherein B is of the formula
wherein R 1 is hydrogen and R 2 is a substituted carboxylic acid, and the substituted carboxylic acid is covalently bound to the linker.
3. The compound of claim 1 or a salt thereof, wherein D is a radioactive isotope of a metal coordinated to a chelating group.
4. The compound of claim 2 or a salt thereof, wherein D is a radioactive isotope of a metal coordinated to a chelating group.
5. A pharmaceutical composition comprising a compound of claim 1 or a salt thereof and at least one pharmaceutically acceptable carrier, excipient, or a combination thereof.
6. The compound of claim 3 or a salt thereof, wherein the radioactive isotope is 111 In.
7. The compound of claim 3 or a salt thereof, wherein the radioactive isotope is 99m Tc.
8. The compound of claim 3 or a salt thereof, wherein the radioactive isotope is 99m Tc.
9. The compound of claim 3 or a salt thereof, wherein the radioactive isotope is 64 Cu.
10. The compound of claim 3 or a salt thereof, wherein the radioactive isotope is 67 Cu.
11. The compound of claim 3 or a salt thereof, wherein the radioactive isotope is 67 Ga.
12. The compound of claim 3 or a salt thereof, wherein the radioactive isotope is 68 Ga.