Double targeted constructs to affect tumor kill
The present technology is directed to compounds, compositions, medicaments, and methods related to the treatment of cancers expressing PSMA. The compounds are of Formulas I & II or pharmaceutically acceptable salts thereof. The present technology is especially well-suited for use in treating prostate cancer.
1. A compound of Formula II
or a pharmaceutically acceptable salt thereof, wherein
X 2 is 124 I, 125 I, 127 I, 131 I, 211 At, or Sn(R 8 ) 3 ;
R 5 , R 6 , and R 7 are each independently H, methyl, benzyl, 4-methoxybenzyl, or tert-butyl;
R 8 is independently at each occurrence an alkyl group;
W 1 is a bond or —NH-alkylene-; and
p is 0, 1, 2, or 3.
2. The compound of claim 1 , wherein X 1 is 124 I, 125 I, 131 I, or 211 At.
3. A composition comprising a compound of claim 2 and a pharmaceutically acceptable carrier.
4. A pharmaceutical composition for treating a cancer expressing prostate specific membrane antigen (“PSMA”), the composition comprising an effective amount of the compound of claim 2 for treating the cancer and a pharmaceutically acceptable excipient wherein the cancer is non-small cell lung cancer, small cell lung cancer, bladder cancer, colon cancer, primary gastric adenocarcinoma, primary colorectal adenocarcinoma, renal cell carcinoma, or prostate cancer.
5. A method comprising administering a compound of claim 2 to a subject suffering from non-small cell lung cancer, small cell lung cancer, bladder cancer, colon cancer, primary gastric adenocarcinoma, primary colorectal adenocarcinoma, renal cell carcinoma, or prostate cancer.
6. The method of claim 5 , wherein the method comprises administering an effective amount of the compound to the subject.
7. The compound of claim 2 , wherein R 5 , R 6 , and R 7 are each independently H.
8. A composition comprising a compound of claim 7 and a pharmaceutically acceptable carrier.
9. A pharmaceutical composition for treating a cancer expressing prostate specific membrane antigen (“PSMA”), the composition comprising an effective amount of the compound of claim 7 for treating the cancer and a pharmaceutically acceptable excipient wherein the cancer is non-small cell lung cancer, small cell lung cancer, bladder cancer, colon cancer, primary gastric adenocarcinoma, primary colorectal adenocarcinoma, renal cell carcinoma, or prostate cancer.
10. A method comprising administering an effective amount of a compound of claim 7 to a subject suffering from non-small cell lung cancer, small cell lung cancer, bladder cancer, colon cancer, primary gastric adenocarcinoma, primary colorectal adenocarcinoma, renal cell carcinoma, or prostate cancer.
11. The method of claim 10 , wherein administering the compound comprises parenteral administration.
12. The compound of claim 1 , wherein the compound of Formula II is a compound of Formula IIa
or a pharmaceutically acceptable salt thereof.
13. The compound of claim 12 , wherein X 2 is 124 I, 125 I, 131 I, or 211 At and wherein R 5 , R 6 , and R 7 are each independently H.
14. The compound of claim 13 , wherein X 2 is 211 At.
15. A composition comprising a compound of claim 13 and a pharmaceutically acceptable carrier.
16. A pharmaceutical composition for treating a cancer expressing prostate specific membrane antigen (“PSMA”), the composition comprising an effective amount of the compound of claim 13 for treating the cancer and a pharmaceutically acceptable excipient wherein the cancer is non-small cell lung cancer, small cell lung cancer, bladder cancer, colon cancer, primary gastric adenocarcinoma, primary colorectal adenocarcinoma, renal cell carcinoma, or prostate cancer.
17. A method comprising administering an effective amount of a compound of claim 13 to a subject suffering from non-small cell lung cancer, small cell lung cancer, bladder cancer, colon cancer, primary gastric adenocarcinoma, primary colorectal adenocarcinoma, renal cell carcinoma, or prostate cancer.
18. The method of claim 17 , wherein administering the compound comprises intravenous administration.
19. A pharmaceutical composition for treating a cancer expressing prostate specific membrane antigen (“PSMA”), the composition comprising an effective amount of the compound of claim 14 for treating the cancer and a pharmaceutically acceptable excipient wherein the cancer is non-small cell lung cancer, small cell lung cancer, bladder cancer, colon cancer, primary gastric adenocarcinoma, primary colorectal adenocarcinoma, renal cell carcinoma, or prostate cancer.
20. A method comprising administering an effective amount of a compound of claim 14 to a subject suffering from non-small cell lung cancer, small cell lung cancer, bladder cancer, colon cancer, primary gastric adenocarcinoma, primary colorectal adenocarcinoma, renal cell carcinoma, or prostate cancer, wherein administering the compound comprises parenteral administration.