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-C
or a salt thereof, wherein
B is a ligand of prostate specific membrane antigen (PSMA) that is a urea of two amino acids, wherein the two amino acids are independently selected from asparagine, aspartic acid, cysteine, glutamic acid, lysine, glutamine, arginine, serine, ornithine, threonine and combinations thereof;
L is a divalent linker of 7 to 20 atoms in length, the divalent linker comprising a divalent alkylene group, a cycloalkylenecarbonyl group and a hydrophobic side chain divalent group comprising an arylalkyl side chain; and
C is a chelating group of the formula
wherein * is the point of attachment to the divalent linker;
provided that the divalent linker has a single hydrophobic side chain divalent group in L.
2. The compound of claim 1 , or a salt thereof, wherein the chelating group is chelated to a radioactive metal isotope.
3. The compound of claim 1 , or a salt thereof, wherein the divalent linker is covalently bound to the chelating group through the formation of an amide bond, and the divalent linker is covalently bound to the ligand through the formation of an amide bond.
4. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 , or a salt thereof, and a component selected from the group consisting of carriers, diluents, and excipients, and combinations thereof.
5. A method for treating a disease involving a pathogenic cell population expressing PSMA, the method comprising the step of administering to a patient in need of relief from the disease a therapeutically effective amount of the compound of claim 1 , or a salt thereof, optionally with a component selected from the group consisting of carriers, diluents, and excipients, and combinations thereof.