Organonitro thioether compounds and medical uses thereof
The invention provides organonitro thioether compounds, compositions containing such compounds, isolated organonitro thioether compounds and methods for using such compounds and compositions to treat cancer in a patient. Exemplary organonitro thioether compounds described herein include 2-(3,3-dinitroazetidin-1-yl)-2-oxoethyl thioethers and variants thereof.
1. A method of treating cancer in a human patient, comprising administering to a human patient in need thereof a therapeutically effective amount of a pharmaceutical composition comprising an organonitro compound of Formula I-A to treat the cancer, wherein Formula I-A is represented by:
or a pharmaceutically acceptable salt thereof, wherein:
A 1 is N;
R 1 represents independently for each occurrence hydrogen or methyl;
R 4 is C 1 -C 5 alkyl substituted with one X 1 group and one X 2 group; wherein X 1 is —NH 2 , —N(H)C(O)—C 1 -C 5 alkyl, or —N(H)C(O)—(C 1 -C 5 alkylene)-C(H)(NH 2 )—CO 2 H; and X 2 is —CO 2 H, —CO 2 —C 1 -C 5 alkyl, or —C(O)N(H)CH 2 CO 2 H; and
p represents independently for each occurrence 1 or 2.
2. The method of claim 1 , wherein the cancer is a solid tumor.
3. The method of claim 1 , wherein the cancer is brain cancer, bladder cancer, breast cancer, cervical cancer, colon cancer, colorectal cancer, endometrial cancer, esophageal cancer, leukemia, lung cancer, liver cancer, melanoma, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, renal cancer, stomach cancer, testicular cancer, or uterine cancer.
4. The method of claim 3 , further comprising exposing the cancer to radiation.
5. The method of claim 1 , wherein the cancer is brain cancer, bladder cancer, breast cancer, or cervical cancer.
6. The method of claim 1 , wherein the cancer is colon cancer or colorectal cancer.
7. The method of claim 1 , wherein the cancer is leukemia.
8. The method of claim 1 , wherein the cancer is lung cancer, liver cancer, melanoma, ovarian cancer, pancreatic cancer, or prostate cancer.
9. The method of claim 1 , wherein the cancer is rectal cancer, renal cancer, testicular cancer, or uterine cancer.
10. The method of claim 5 , wherein R 4 is
11. The method of claim 6 , wherein R 4 is
12. The method of claim 7 , wherein R 4 is
13. The method of claim 8 , wherein R 4 is
14. The method of claim 9 , wherein R 4 is
15. The method of claim 3 , wherein the organonitro compound is
or a pharmaceutically acceptable salt thereof.
16. The method of claim 5 , wherein the organonitro compound is
or a pharmaceutically acceptable salt thereof.
17. The method of claim 6 , wherein the organonitro compound is
or a pharmaceutically acceptable salt thereof.
18. The method of claim 7 , wherein the organonitro compound is
or a pharmaceutically acceptable salt thereof.
19. The method of claim 8 , wherein the organonitro compound is
or a pharmaceutically acceptable salt thereof.
20. The method of claim 9 , wherein the organonitro compound is
or a pharmaceutically acceptable salt thereof.