# US 2014/0194463 A1 · Compositions for treatment of cancer

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- Number: US 2014/0194463 A1
- Document ID: US20140194463A1
- Status: Published application
- Kind: A1
- Application number: 13/802,018
- Filed: 2013-03-13
- Published: 2014-07-10
- Earliest claimed: 2013-01-04
- Assignees: NovaRx
- Applicants: NovaRx Corporation
- Inventors: Feridoun KARIMI-BUSHERI; Habib FAKHRAI
- Web page: https://patentgrep.com/patent/US20140194463A1

## CPC

- C07D 471/04: Ortho-condensed systems
- C07D 215/24: attached in position 8
- C07D 251/46: with oxygen or sulfur atoms attached to the two other ring carbon atoms
- C07D 257/06: with nitrogen atoms directly attached to the ring carbon atom
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Compounds that are specifically toxic to cancer stem cells are disclosed.

## Claims

### Claim 1

A pharmaceutical composition comprising as an active ingredient at least one compound of formula (A):
wherein:
Het is pyrrolyl, pyrazoyl, imidazolyl, triazolyl, or tetrazolyl;
R4 and R5 are each independently H or C1-4alkyl;
each X is independently selected from the group consisting of halo, nitro, —OR6, —OCOR6, —COOR6, —R6NCOR6, —CONR62, —COR6, —NR62, —S(O)mR6, —CN, and R7;
wherein R7 is C1-6alkyl, unsubstituted or substituted with halo, OR6, or NR62;
each R6 is independently H or C1-4alkyl;
m is 0, 1, or 2, and
n is 0, 1, 2 or 3;
or a tautomer thereof;
or a pharmaceutically acceptable salt or solvate thereof.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein Het is an imidazolyl, triazolyl, or tetrazolyl.

### Claim 3 (depends on 1)

The pharmaceutical composition of claim 1, wherein Het is tetrazolyl.

### Claim 4 (depends on 1)

The pharmaceutical composition of claim 1, wherein R4 and R5 are each independently H, methyl, or ethyl.

### Claim 5 (depends on 1)

The pharmaceutical composition of claim 1, wherein R4 and R5 are both H.

### Claim 6 (depends on 1)

The pharmaceutical composition of claim 1, wherein each X is independently selected from the group consisting of chloro, bromo, fluoro, nitro, methoxy, ethoxy, isopropoxy, acetoxy, methoxycarbonyl, —NHCO-methyl, —CONH(methyl), —CONH2, —CON(methyl)2, acetyl, amino, methylamino, dimethylamino, methylsulfonyl, cyano, methyl, ethyl, propyl, isopropyl, fluoromethyl, and trifluoromethyl.

### Claim 7 (depends on 1)

The pharmaceutical composition of claim 1, wherein each X is independently chloro, bromo, fluoro, cyano, methyl, trifluoromethyl, or methoxy.

### Claim 8 (depends on 1)

The pharmaceutical composition of claim 1, wherein n is 2.

### Claim 9 (depends on 1)

The pharmaceutical composition of claim 1, wherein the compound is:
or a pharmaceutically acceptable salt thereof.

### Claim 10

A pharmaceutical composition comprising as an active ingredient at least one compound of formula (B):
wherein:
zero or one of A1-4 is N and the others are CH;
R8 is —NO2, —CO2H, —PO3R9, —SO3H, or —SO2R9;
where R9 is OH or C1-4alkyl;
each X is independently selected from the group consisting of halo, nitro, —OR10, —OCOR10, —COOR10, —R10NCOR10, —CONR102, —COR10, —NR102, —S(O)MR10, —CN, and R11;
Y is O or —NR10;
R11 is C1-6alkyl, unsubstituted or substituted with halo, —OR10, or —NR102;
n is 0, 1, 2 or 3;
m is 0, 1, or 2; and
each R10 is independently H or C1-4alkyl;
or a pharmaceutically acceptable salt or solvate thereof.

### Claim 11 (depends on 10)

The pharmaceutical composition of claim 10, wherein A1-4 are each CH.

### Claim 12 (depends on 10)

The pharmaceutical composition of claim 10, wherein R8 is —NO2, —CO2H, —PO3H, or —SO3H.

### Claim 13 (depends on 10)

The pharmaceutical composition of claim 10, wherein R8 is —NO2.

### Claim 14 (depends on 10)

The pharmaceutical composition of claim 10, wherein R9 is OH or methyl.

### Claim 15 (depends on 10)

The pharmaceutical composition of claim 10, wherein each X is independently chloro, bromo, fluoro, cyano, methyl, trifluoromethyl, or methoxy.

### Claim 16 (depends on 10)

The pharmaceutical composition of claim 10, wherein Y is O.

### Claim 17 (depends on 10)

The pharmaceutical composition of claim 10, wherein n is 0.

### Claim 18 (depends on 10)

The pharmaceutical composition of claim 10, wherein the compound of formula (B) is:
or a pharmaceutically acceptable salt thereof.

### Claim 19 (depends on 1)

A method to treat cancer in a subject in need thereof comprising administering to said subject an effective amount of the composition of claim 1.

### Claim 20 (depends on 10)

A method to treat cancer in a subject in need thereof comprising administering to said subject an effective amount of the composition of claim 10.