Double targeted constructs to affect tumor kill

Patent metadata

Field	Value
Publication number	US-10716772-B2
Application number	US-201916246422-A
Country	US
Kind code	B2
Filing date	Jan 11, 2019
Priority date	Jun 23, 2016
Publication date	Jul 21, 2020
Grant date	Jul 21, 2020

Abstract

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.

First claim

What is claimed is:

1. A compound of Formula I

or a pharmaceutically acceptable salt thereof, wherein
X 1 is 124 I, 125 I, 127 I, 131 I, 211 At or Sn(R 4 ) 3 ;
R 1 , R 2 , and R 3 are each independently H, methyl, benzyl, 4-methoxybenzyl, or tert-butyl;
R 4 is independently at each occurrence an alkyl group;
n is 1 or 2; and
m is 1, 2, or 3.

2. The compound of claim 1 , wherein when n is 2, then m is not 2.

3. The compound of claim 1 , wherein X 1 is 124 I, 125 I, 131 I, or 211 At.

4. The compound of claim 3 , wherein R 5 , R 6 , and R 7 are each independently H.

5. The compound of claim 1 , wherein the compound of Formula I is a compound of Formula Ia

or a pharmaceutically acceptable salt thereof.

6. The compound of claim 5 , 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.

7. The compound of claim 6 , wherein X 2 is 211 At.

8. A composition comprising a compound of claim 3 and a pharmaceutically acceptable carrier.

9. A composition comprising a compound of claim 4 and a pharmaceutically acceptable carrier.

10. A composition comprising a compound of claim 6 and a pharmaceutically acceptable carrier.

11. A pharmaceutical composition for treating a cancer expressing prostate specific membrane antigen (“PSMA”), the composition comprising an effective amount of the compound of claim 3 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.

12. A pharmaceutical composition for treating a cancer expressing prostate specific membrane antigen (“PSMA”), the composition comprising an effective amount of the compound of claim 4 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.

13. A pharmaceutical composition for treating a cancer expressing prostate specific membrane antigen (“PSMA”), the composition comprising an effective amount of the compound of claim 6 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.

14. A method comprising administering an effective amount of a compound of claim 3 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.

15. The method of claim 14 , wherein administering the compound comprises parenteral administration.

16. A method comprising administering an effective amount of a compound of claim 4 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.

17. The method of claim 16 , wherein administering the compound comprises parenteral administration.

18. A method comprising administering an effective amount of a compound of claim 6 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.

19. The method of claim 18 , wherein administering the compound comprises parenteral administration.

Assignees

• Univ Cornell

Inventors

• Babich John W
• Kelly James M
• Amor-Coarasa Alejandro
• Ponnala Shashikanth

Classifications

• G01N33/57555

  of the prostate · CPC title

• G01N33/5759

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• G01N2500/04

  Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A) · CPC title

• G01N33/60

  involving radioactive labelled substances · CPC title

• G01N33/58

  involving labelled substances (G01N33/53 takes precedence) · CPC title