CONJUGATES FOR TREATING DISEASES CAUSED BY PSMA EXPRESSING CELLS
The invention described herein pertains to the diagnosis, imaging, and/or treatment of pathogenic cell populations. In particular, the invention described herein pertains to the diagnosis, imaging, and/or treatment of diseases caused by PSMA expressing cells, such as prostate cancer cells, using compounds capable of targeting PSMA expressing cells.
1 . A conjugate of the formula
or a pharmaceutically acceptable salt thereof, wherein B comprises a urea of lysine and an amino acid selected from the group consisting of aspartic acid, glutamic acid, and homoglutamic acid, L is a polyvalent linker comprising (i) an alkylene or an alkylenecarbonyl, each of which is substituted with a guanidinoalkyl, an alkyl carboxylate or an arylalkyl, and (ii) an alkylene, a cycloalkylene, an alkylenecycloalkyl, or a cycloalkylenecarbonyl, and D is a radioactive isotope of a metal coordinated to a chelating group, wherein the chelating group is covalently attached to L.
2 - 29 . (canceled)
30 . The conjugate of claim 1 , or the pharmaceutically acceptable salt thereof, wherein B is selected from the group consisting of
31 . The conjugate of claim 30 , or the pharmaceutically acceptable salt thereof, wherein B
32 . The conjugate of claim 1 , or the pharmaceutically acceptable salt thereof, wherein L forms an amide, a thioamide, a urea, or a thiourea with the lysine.
33 . The conjugate of claim 32 , or the pharmaceutically acceptable salt thereof, wherein L forms an amide or a urea with the lysine.
34 . The conjugate of claim 33 , or the pharmaceutically acceptable salt thereof, wherein L forms an amide with the lysine.
35 . The conjugate of claim 1 , or the pharmaceutically acceptable salt thereof, wherein L is not a releasable linker.
36 . The conjugate of claim 1 , or the pharmaceutically acceptable salt thereof, wherein the amino acid is glutamic acid.
37 . The conjugate of claim 31 , or the pharmaceutically acceptable salt thereof, wherein the linker comprises an alkylene substituted with an arylalkyl or an alkylenecarbonyl substituted with an arylalkyl.
38 . The conjugate of claim 37 , or the pharmaceutically acceptable salt thereof, wherein the arylalkyl comprises a naphthyl.
39 . The conjugate of claim 38 , or the pharmaceutically acceptable salt thereof, wherein the naphthyl comprises a 2-naphthyl.
40 . The conjugate of claim 38 , or the pharmaceutically acceptable salt thereof, wherein the arylalkyl is of the formula
wherein * represents a point of covalent attachment to the alkylene or the alkylenecarbonyl.
41 . The conjugate of claim 1 , or the pharmaceutically acceptable salt thereof, wherein the cycloalkylene, alkylenecycloalkyl, or cycloalkylenecarbonyl comprises a cyclohexyl group.
42 . The conjugate of claim 31 , or the pharmaceutically acceptable salt thereof, wherein the cycloalkylene, alkylenecycloalkyl, or cycloalkylenecarbonyl comprises a cyclohexyl group.
43 . The conjugate of claim 37 , or the pharmaceutically acceptable salt thereof, wherein the cycloalkylene, alkylenecycloalkyl, or cycloalkylenecarbonyl comprises a cyclohexyl group.
44 . The conjugate of claim 39 , or the pharmaceutically acceptable salt thereof, wherein the cycloalkylene, alkylenecycloalkyl, or cycloalkylenecarbonyl comprises a cyclohexyl group.
45 . The conjugate of claim 40 , or the pharmaceutically acceptable salt thereof, wherein the cycloalkylene, alkylenecycloalkyl, or cycloalkylenecarbonyl comprises a cyclohexyl group.
46 . The conjugate of claim 1 , or the pharmaceutically acceptable salt thereof, wherein L comprises a chain of at least about 8 atoms.
47 . The conjugate of claim 1 , or the pharmaceutically acceptable salt thereof, wherein L comprises a chain of at least about 9 atoms.
48 . The conjugate of claim 44 , or the pharmaceutically acceptable salt thereof, wherein L comprises a chain of at least about 9 atoms.