# US 12,215,108 B2 · Development of potential antidotes for arsenicals

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 12,215,108 B2
- Document ID: US12215108B2
- Status: Granted
- Kind: B2
- Application number: 18/095,429
- Filed: 2023-01-10
- Published: 2023-07-13
- Granted: 2025-02-04
- Earliest claimed: 2022-01-10
- Assignees: Southern Research Institute; The UAB Research Foundation; The United States Government as represented by the Department of Veterans Affairs
- Applicants: Southern Research Institute; UAB Research Foundation; The United States Government as represented by the Department of Veterans Affairs
- Inventors: Mark J. Suto; Bini Mathew; Corinne E. Augelli-Szafran; Marina Fosso Yatchang; Mohammad Athar; Anupam Agarwal; Ritesh Kumar Srivastava; Suhail Muzaffar; Jasim Khan
- Web page: https://patentgrep.com/patent/US12215108B2

## CPC

- C07D 473/32: Nitrogen atom
- A61P 39/02: Antidotes
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure is concerned with purine diamine compounds for the treatment of conditions associated with BRD4, RIP3K, and/or IL6 signaling dysfunction such as, for example, cancer (e.g., lung cancer, skin cancer, bladder cancer, kidney cancer, liver cancer), arsenicosis, arsenic poisoning, inflammation, skin lesions, dysfunction of systemic organs, and skin blisters. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

## Claims

### Claim 1

A compound having a structure represented by a formula:
wherein each of R1a, R1b, R1c, R1d, and R1e is independently selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl;
wherein each of R2 and R3 is independently selected from hydrogen and C1-C4 alkyl;
wherein Cy1 is a structure having a formula selected from:
wherein n, when present, is 0 or 1;
wherein Z, when present, is selected from —O—, —S—, and —NR20—;
wherein R20, when present, is selected from hydrogen and C1-C4 alkyl;
wherein each of R10a, R10b, R10c, R10d, R10e, and R10f, when present, is independently selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl;
wherein each of R11a and R11b, when present, is independently selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl;
wherein each of R12a, R12b, R12c, and R12d, when present, is independently selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl; and
wherein R13, when present, is selected from —OH, —NH2, C1-C4 alkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino; and
wherein Cy2 is a structure having a formula selected from:
wherein m, when present, is 0 or 1;
wherein Q, when present, is selected from —O—, —S—, and —NR21—;
wherein R21, when present, is selected from hydrogen and C1-C4 alkyl;
wherein each of R14a, R14b, R14c, R14d, R14e, and R14f, when present, is independently selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl;
wherein each of R15a and R15b, when present, is independently selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl;
wherein each of R16a, R16b, R16c, and R16d, when present, is independently selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl; and
wherein R17, when present, is selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, —CO2H, and —CO2 (C1-C4 alkyl),
provided that when Cy1 is
and at least seven of R10a, R10b, R10c, R10d, R10e, R10f, R11a, and R11b are hydrogen, then each of R1a, R1c, and R1e is halogen,
provided that when Cy1 is
then Cy2 is
provided that when Cy1 is
and Cy2 is
then R17 is a non-hydrogen group, and
provided that when Cy1 is
Cy2 is
and at least seven of R14a, R14b, R14c, R14d, R14e, R14f, R15a, and R15b are hydrogen, then each of R12a, R12b, R12c, and R12d is hydrogen,
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound of claim 1, wherein each of R1a, R1b, R1c, R1d, and R1e is independently selected from hydrogen and halogen.

### Claim 3 (depends on 1)

The compound of claim 1, wherein each of R1a, R1b, R1c, R1d, and R1e is hydrogen.

### Claim 4 (depends on 1)

The compound of claim 1, wherein Cy1 is a structure represented by a formula:

### Claim 5 (depends on 1)

The compound of claim 1, wherein Cy1 is a structure represented by a formula selected from:

### Claim 6 (depends on 1)

The compound of claim 1, wherein Cy1 is a structure represented by a formula:

### Claim 7 (depends on 1)

The compound of claim 1, wherein Cy2 is a structure represented by a formula:

### Claim 8 (depends on 1)

The compound of claim 1, wherein Cy2 is a structure represented by a formula:

### Claim 9 (depends on 1)

The compound of claim 1, wherein the compound has a structure represented by a formula:

### Claim 10 (depends on 1)

The compound of claim 1, wherein the compound has a structure represented by a formula:
wherein each of R1a, R1c, and R1e is halogen.

### Claim 11 (depends on 1)

The compound of claim 1, wherein the compound has a structure represented by a formula:
wherein R17 is selected from —OH, —NH2, C1-C4 alkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino.

### Claim 12 (depends on 1)

The compound of claim 1, wherein the compound has a structure represented by a formula:
wherein R17, when present, is selected from halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, C1-C4 aminoalkyl, —CO2H, and —CO2(C1-C4 alkyl).

### Claim 13 (depends on 1)

The compound of claim 1, wherein the compound has a structure represented by a formula:
wherein one of R14a, R14b, R14c, R14d, R14e, R14f, R15a, and R15b, when present, is selected from hydrogen, halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and C1-C4 aminoalkyl, and wherein the remaining R14a, R14b, R14c, R14d, R14e, R14f, R15a, and R15b groups are hydrogen.

### Claim 14 (depends on 1)

The compound of claim 1, wherein the compound is selected from:

### Claim 15 (depends on 1)

A pharmaceutical composition comprising an effective amount of the compound of claim 1, and a pharmaceutically acceptable carrier.