# US 11,896,564 B2 · Medical treatment for pathologic inflammation

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- Number: US 11,896,564 B2
- Document ID: US11896564B2
- Status: Granted
- Kind: B2
- Application number: 17/264,924
- Filed: 2019-08-15
- Published: 2022-03-24
- Granted: 2024-02-13
- Earliest claimed: 2018-08-15
- Assignees: Pharmacyl AB
- Applicants: Pharmacyl AB
- Inventors: Gunnar Hedlund; Anders Björk
- Web page: https://patentgrep.com/patent/US11896564B2

## CPC

- A61K 31/166: having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
- A61K 31/196: the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
- A61K 31/655: Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, for use in combination with a 5-ASA agent, in the treatment of a disease resulting from pathologic inflammation. The combination of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof and 5-ASA agent and use of such combination. A kit-of-parts and a pharmaceutical composition comprising such a combination.

## Claims

### Claim 1

A method for the treatment of a disease resulting from pathologic inflammation, comprising administering a therapeutically effective amount of a compound of formula (I)
or a pharmaceutically acceptable salt or solvate thereof; wherein
R1 is selected from C1-C6 alkyl and C3-C6 cycloalkyl;
R2 is selected from H and C1-C3 alkyl;
R3, R4, R5, and R6 are independently selected from hydrogen, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 alkylthio, and halogen, wherein any alkyl is optionally substituted with one or more fluoro;
R7 is selected from hydrogen and C1-C3 alkyl; and
R8 and R9 are independently selected from C1-C6 alkyl;
wherein the treatment also includes administration of a 5-ASA agent selected from mesalazine, sulfasalazine, olsalazine, and balsalazide or a pharmaceutically acceptable salt or solvate thereof.

### Claim 2 (depends on 1)

The method according to claim 1, wherein
R3, R4, R5, and R6 are independently selected from hydrogen, C1-C2 alkyl, C1-C2 alkoxy, C1-C2 alkylthio, halogen, and trifluoromethyl;
R7 is selected from hydrogen and C1-C3 alkyl; and
R8 and R9 are independently selected from C1-C6 alkyl
or a pharmaceutically acceptable salt or solvate thereof.

### Claim 3 (depends on 1)

The method according to claim 1, wherein at least two of R3, R4, R5, and R6 are hydrogen.

### Claim 4 (depends on 1)

The method according to claim 1, wherein
R1 is selected from C1-C3 alkyl;
each one of R2, R4, R5, R6 and R7 is hydrogen; and
R8 and R9 are independently selected from C1-C4 alkyl.

### Claim 5 (depends on 1)

The method according to claim 1, wherein
the compound of formula (I) is selected from
4-acetamido-3-chloro-N-[2-(diethylamino)ethyl]benzamide,
4-propanamido-3-chloro-N-[2-(diethylamino)ethyl]benzamide,
4-isobutanamido-3-chloro-N-[2-(diethylamino)ethyl]benzamide,
4-acetamido-N-[2-(diethylamino)ethyl]benzamide,
N-[2-(diethylamino)ethyl]-4-(propanamido)benzamide, and
N-[2-(diethylamino)ethyl]-4-(isobutanamido)benzamide.

### Claim 6 (depends on 5)

The method according to claim 5, wherein the compound of formula (I) is 4-acetamido-3-chloro-N-[2-(diethylamino)ethyl]benzamide.

### Claim 7 (depends on 5)

The method according to claim 5, wherein the compound of formula (I) is 4-propanamido-3-chloro-N-[2-(diethylamino)ethyl]-benzamide.

### Claim 8 (depends on 5)

The method according to claim 5, wherein the compound of formula (I) is 4-isobutanamido-3-chloro-N-[2-(diethylamino)ethyl]-benzamide.

### Claim 9 (depends on 5)

The method according to claim 5, wherein the compound of formula (I) is 4-acetamido-N-[2-(diethylamino)ethyl]benzamide.

### Claim 10 (depends on 1)

The method according to claim 1, wherein the disease is an inflammatory bowel disease.

### Claim 11 (depends on 10)

The method according to claim 10, wherein the inflammatory bowel disease is ulcerative colitis.

### Claim 12 (depends on 10)

The method according to claim 10, wherein the inflammatory bowel disease is Crohn's disease.

### Claim 13

A combination of:
(i) a compound of formula (I)
or a pharmaceutically acceptable salt or solvate thereof; wherein
R1 is selected from C1-C6 alkyl and C3-C6 cycloalkyl;
R2 is selected from H and C1-C3 alkyl;
R3, R4, R5, and R6 are independently selected from hydrogen, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 alkylthio, and halogen, wherein any alkyl is optionally substituted with one or more fluoro;
R7 is selected from hydrogen and C1-C3 alkyl; and
R8 and R9 are independently selected from C1-C6 alkyl; and
(ii) a 5-ASA agent selected from mesalazine, sulfasalazine, olsalazine, and balsalazide or a pharmaceutically acceptable salt or solvate thereof.

### Claim 14 (depends on 13)

The combination according to claim 13, wherein
R3, R4, R5, and R6 are independently selected from hydrogen, C1-C2 alkyl, C1-C2 alkoxy, C1-C2 alkylthio, halogen, and trifluoromethyl;
R7 is selected from hydrogen and C1-C3 alkyl; and
R8 and R9 are independently selected from C1-C6 alkyl;
or a pharmaceutically acceptable salt or solvate thereof.

### Claim 15 (depends on 13)

The combination according to claim 13, wherein at least two of R3, R4, R5, and R6 are hydrogen.

### Claim 16 (depends on 13)

The combination according to claim 13, wherein
R1 is selected from C1-C3 alkyl;
each one of R2, R4, R5, R6 and R7 is hydrogen; and
R8 and R9 are independently selected from C1-C4 alkyl.

### Claim 17 (depends on 13)

The combination according to claim 13, wherein the compound of formula (I) is selected from
4-acetamido-3-chloro-N-[2-(diethylamino)ethyl]benzamide,
4-propanamido-3-chloro-N-[2-(diethylamino)ethyl]benzamide,
4-isobutanamido-3-chloro-N-[2-(diethylamino)ethyl]benzamide,
4-acetamido-N-[2-(diethylamino)ethyl]benzamide,
N-[2-(diethylamino)ethyl]-4-(propanamido)benzamide, and
N-[2-(diethylamino)ethyl]-4-(isobutanamido)benzamide.

### Claim 18 (depends on 17)

The combination according to claim 17, wherein the compound of formula (I) is 4-acetamido-3-chloro-N-[2-(diethylamino)ethyl]benzamide.

### Claim 19 (depends on 17)

The combination according to claim 17, wherein the compound of formula (I) is 4-propanamido-3-chloro-N-[2-(diethylamino)ethyl]benzamide.

### Claim 20 (depends on 17)

The combination according to claim 17, wherein the compound of formula (I) is 4-isobutanamido-3-chloro-N-[2-(diethylamino)ethyl]benzamide.

### Claim 21 (depends on 17)

The combination according to claim 17, wherein the compound of formula (I) is 4-acetamido-N-[2-(diethylamino)ethyl]benzamide.

### Claim 22 (depends on 13)

A pharmaceutical composition comprising a combination as defined in claim 13, and optionally a pharmaceutically acceptable excipient.

### Claim 23 (depends on 13)

A kit-of-parts comprising a combination as defined in claim 13, wherein each one of components (i) and (ii) is optionally formulated in admixture with a pharmaceutically acceptable excipient.