N-(4-(bis(4-(dimethylamino)phenyl)methylene)-8-(dimethylamino)

Patent metadata

Field	Value
Publication number	US-9567291-B2
Application number	US-201414786580-A
Country	US
Kind code	B2
Filing date	Apr 25, 2014
Priority date	Apr 25, 2013
Publication date	Feb 14, 2017
Grant date	Feb 14, 2017

Abstract

This disclosure relates to N-(4-(bis(4-(dimethylamino)phenyl)methylene)-8 -(dimethylamino)naphthalen-1(4H)-ylidene)-N-methylmethanaminium, derivatives, and uses related thereto. In certain embodiments, the disclosure relates to compounds of formula I. In certain embodiments, the disclosure relates to methods of treating or preventing Nox related diseases and conditions comprising administering an effective amount of compounds disclosed herein to a subject in need thereof. In certain embodiments, the Nox related disease or condition is cancer.

First claim

The invention claimed is:

1. A compound comprising formula I:

prodrugs, esters, or salts thereof wherein,
R 1 , R 2 , R 3 , and R 4 are methyl, propyl, or optionally substituted with one or more, the same or different, R 20 or R 21 ;
R 5 , R 6 , R 7 , R 10 , R 11 , R 14 , R 15 , and R 16 are individually and independently alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl) 2 amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R 5 , R 6 , R 7 , R 10 , R 11 , R 14 , R 15 , and R 16 are optionally substituted with one or more, the same or different, R 20 ;
R 8 , R 9 , R 12 , and R 13 are methyl;
R 20 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkanoyl, alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein R 20 is optionally substituted with one or more, the same or different, R 21 ; and
R 21 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, Nmethyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, or heterocyclyl.

2. The compound of claim 1 , wherein R 1 , R 2 , R 3 and R 4 are methyl.

3. The compound of claim 1 , having the formula: N-(4-(bis(4-(dimethylamino)phenyl)methylene)-8-(dimethylamino)naphthalen-1(4H)-ylidene)-N-methylmethanaminium.

4. A pharmaceutical composition comprising a compound of claim 1 or salt thereof and a pharmaceutically acceptable excipient.

5. A pharmaceutical composition of claim 4 , further comprising a second therapeutic agent.

6. The pharmaceutical composition of claim 5 , wherein the second therapeutic agent is an anti-cancer agent.

7. A method of treating cancer comprising administering an effective amount of a compound in claim 1 to a subject in need thereof.

8. The method of claim 7 , wherein the subject is diagnosed with or at risk of cancer.

9. The method of claim 7 , wherein the compound is administered in combination with a second therapeutic agent.

10. The method of claim 7 , wherein the cancer is selected from bladder cancer, lung cancer, breast cancer, melanoma, colon and rectal cancer, non-hodgkin lymphoma, burkitt lymphoma, endometrial cancer, pancreatic cancer, kidney cancer, prostate cancer, leukemia, thyroid cancer, and brain cancer.

11. The method of claim 7 , wherein the compound is administered in combination with a second anticancer agent.

Assignees

• Univ Emory

Inventors

• Arbiser Jack

Classifications

• C07D223/28

  having a single bond between positions 10 and 11 · CPC title

• C07C251/22

  Quinone imines · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07C251/30 Primary

  having nitrogen atoms of imino groups quaternised · CPC title

• A61K31/15

  Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) {; Imines (C—N=C)} · CPC title