Bis-diazeniumdiolate compounds as anti-cancer agents

Patent metadata

Field	Value
Publication number	US-10556875-B2
Application number	US-201816155525-A
Country	US
Kind code	B2
Filing date	Oct 9, 2018
Priority date	Oct 10, 2017
Publication date	Feb 11, 2020
Grant date	Feb 11, 2020

Abstract

A series of double-component, bis O 2 -aryl diazeniumdiolate derivatives are provided, of which each molecule can release up to four nitric oxide molecules. These compounds show cytotoxic activities to cancer cells, such as human leukemia, breast cancer and lung cancer. Among them, the compound 3 showed the highest specific activity against human leukemia cells.

First claim

What is claimed is:

1. A compound selected from formula I:

wherein:
X is CH or N; and
L is selected from C 1 -C 10 alkyldiyl, C 1 -C 10 alkyldiyl-(C 3 -C 6 cycloalkyldiyl), and C 1 -C 10 alkyldiyl-(C 3 -C 6 cycloalkyldiyl)-C 1 -C 10 alkyldiyl, where alkyldiyl and cycloalkyldiyl are independently and optionally substituted with one or more groups selected from halo, hydroxy, nitro, cyano, (C 1 -C 6 ) alkoxy, and oxo (═O);
or a pharmaceutically-acceptable salt thereof.

2. The compound of claim 1 which is a compound of formulae Ia, Ib, or Ic:

where m and n are independently selected from 1, 2, and 3.

3. The compound of claim 1 wherein X is CH.

4. The compound of claim 1 wherein X is N.

5. The compound of claim 1 wherein L is optionally substituted C 1 -C 10 alkyldiyl.

6. The compound of claim 1 wherein L is selected from —CH 2 —, —CH 2 CH 2 —, and —CH 2 CH 2 CH 2 —.

7. The compound of claim 1 wherein L is optionally substituted C 1 -C 10 alkyldiyl-(C 3 -C 6 cycloalkyldiyl).

8. The compound of claim 1 wherein L is optionally substituted C 1 -C 10 alkyldiyl-(C 3 -C 6 cycloalkyldiyl)-C 1 -C 10 alkyldiyl.

9. A compound selected from compounds 1-4:

10. A pharmaceutical composition comprising a compound of formula I as described in claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, glidant, or excipient.

11. A method for treating cancer in an animal in need thereof, comprising administering a therapeutically-effective amount of a compound of formula I as described in claim 1 , or a pharmaceutically acceptable salt thereof, to the said animal; wherein the cancer is selected from pancreatic cancer, bile duct carcinoma, neuroblastoma, colon cancer, breast cancer, myeloma, gastric cancer, liver cancer, gliblastoma, ovarian cancer, colorectal cancer, non-Hodgkin lymphoma, lung cancer, prostate cancer, small-cell lung cancer, large cell lung cancer, kidney cancer, esophageal cancer, stomach cancer, cervical cancer or lymphoma tumors.

12. The method of claim 11 wherein the cancer is breast cancer.

13. A method for inhibiting cancer cell growth in an animal in need thereof, comprising administering an inhibitory effective amount of a compound of formula I as described in claim 1 , or a pharmaceutically acceptable salt thereof, to the said animal; wherein the cancer is selected from pancreatic cancer, bile duct carcinoma, neuroblastoma, colon cancer, breast cancer, myeloma, gastric cancer, liver cancer, glioblastoma, ovarian cancer, colorectal cancer, non-Hodgkin lymphoma, lung cancer, prostate cancer, small-cell lung cancer, large cell lung cancer, kidney cancer, esophageal cancer, stomach cancer, cervical cancer or lymphoma tumors.

14. The method of claim 13 wherein the cancer cell is a breast cancer cell.

Assignees

• Univ Arizona State

Inventors

• Chen Shengxi

Classifications

• C07D295/30 Primary

  non-acylated · CPC title

• C07D211/98

  Nitrogen atom · CPC title

• A61P35/00

  Antineoplastic agents · CPC title