Heterodimers of glutamic acid
View Patent ↗Compounds of Formula (Ia) wherein R is a C 6 -C 12 substituted or unsubstituted aryl, a C 6 -C 12 substituted or unsubstituted heteroaryl, a C 1 -C 6 substituted or unsubstituted alkyl or —NR′R′, Q is C(O), O, NR′, S, S(O) 2 , C(O) 2 (CH2)p Y is C(O), O, NR′, S, S(O) 2 , C(O) 2 (CH2)p Z is H or C 1 -C 4 alkyl, R′ is H, C(O), S(O) 2 , C(O) 2 , a C 6 -C 12 substituted or unsubstituted aryl, a C 6 -C 12 substituted or unsubstituted heteroaryl or a C 1 -C 6 substituted or unsubstituted alkyl, when substituted, aryl, heteroaryl and alkyl are substituted with halogen, C 6 -C 12 heteroaryl, —NR′R′ or COOZ, which have diagnostic and therapeutic properties, such as the treatment and management of prostate cancer and other diseases related to NAALADase inhibition. Radiolabels can be incorporated into the structure through a variety of prosthetic groups attached at the X amino acid side chain via a carbon or hetero atom linkage.
1. A method of imaging one or more organs or tissues or both of a mammal comprising: (A) administering to a mammal an effective amount of a compound of Formula (I)
wherein R is a phenyl moiety substituted with a radiohalogen, or —NHR′,
Q is NH,
Y is C(O), O, NR′, S(O) 2 , C(O) 2 , or (CH 2 ) p ,
Z is H or C 1 -C 4 alkyl,
m is 3 or 4,
n is 0 or 1,
p is 0, 1, 2, 3, 4, 5 or 6, and
R′ is a phenyl moiety substituted with a radiohalogen,
or a pharmaceutically acceptable salt of the compound of Formula (I), which the compound binds Prostate Specific Membrane Antigen (PSMA);
(B) obtaining an image; and
(C) determining from the image the presence of PSMA.
2. The method of claim 1 , wherein the one or more organs or tissues or both includes prostate, prostate tissue or prostate cancer tissue, kidney tissue, brain tissue, vascular tissue, or tumor tissue.
3. The method of claim 1 , wherein
n is 0 or 1;
m is 4;
Y is C(O) or CH 2 ; and
R is a phenyl moiety substituted with a radiohalogen.
4. The method of claim 1 , wherein the compound is:
wherein the hydrogen of the carboxy groups of any of the above compounds can be substituted with C 1 -C 4 alkyl, and
X is selected from the group consisting of I-123, I-125, I-131, I-124, Br-75, Br-77, and F-18.
5. The method of claim 1 , wherein the compound is:
wherein I* is I-123, I-124, I-125 or I-131, Br* is Br-75 or Br-77, and F* is F-18.
6. The method of claim 1 , wherein the compound is of the Formula (II):
wherein R, Q, Y, Z, m and n are as defined in claim 1 .
7. The method of claim 1 , wherein the compound is of Formula Iib:
wherein —Y—R is selected from the group consisting of:
wherein X is selected from the group consisting of: I-123, I-125, I-131, I-124, Br-75, Br-77, and F-18.
8. The method of claim 1 , wherein the compound is of the following structure:
wherein the hydrogen of the carboxy groups of the compound or salt can be substituted with C 1 -C 4 alkyl; and
X is selected from the group consisting of: I-123, I-125, I-131, or I-124.
9. The method of claim 1 , wherein the compound is selected from the group consisting of:
wherein Cl* is Cl-35 and Br* is Br-75 or Br-77.
10. The method of claim 1 , wherein the compound is selected from the group consisting of:
wherein I* is I-123, I-124, I-125 or I-131.
11. The method of claim 1 , wherein the compound is selected from the group consisting of:
wherein I* is I-123, I-124, I-125 or I-131.
12. The method of claim 1 , wherein the radiohalogen is an imaging radiohalogen or a therapeutic radiohalogen.
13. The method of claim 8 having the formula:
wherein I* is I-123, I-124, I-125 or I-131.
14. The method of claim 1 , wherein the compound is of the following structure:
wherein the hydrogen of the carboxy groups of the compound or salt can be substituted with C 1 -C 4 alkyl; and X is selected from the group consisting of I-123, I-125, I-131, I-124, Br-75, Br-77, and F-18.
15. The method of claim 1 , wherein the compound is of the following structure:
wherein the hydrogen of the carboxy groups of the compound or salt can be substituted with C 1 -C 4 alkyl; and
X is selected from the group consisting of: I-123, I-125, I-131, I-124, Br-75, Br-77, and F-18.
16. A method of imaging one or more organs or tissues or both of a mammal comprising administering to a mammal an effective amount of a compound having the formula:
wherein X is selected from the group consisting of: I-123, I-125, I-131, I-124, Br-75, Br-77, and F-18;
or a pharmaceutically acceptable salt thereof.
17. A method of imaging one or more organs or tissues or both of a mammal comprising: (A) administering to a mammal an effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein the compound is
wherein the compound binds Prostate Specific Membrane Antigen (PSMA), and wherein X is selected from the group consisting of I-123, I-125, I-131, I-124, Br-75, Br-77, and F-18;
(B) obtaining an image; and
(C) determining from the image the presence of PSMA.
18. The method of claim 17 , wherein the one or more organs or tissues or both includes prostate, prostate tissue or prostate cancer tissue, kidney tissue, brain tissue, vascular tissue, or tumor tissue.
19. The method of claim 17 , wherein the compound is administered in a pharmaceutically effective dosage.