# US 12,213,970 B2 · Pyridinyl sulfonamide derivatives, pharmaceutical compositions and uses thereof

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- Number: US 12,213,970 B2
- Document ID: US12213970B2
- Status: Granted
- Kind: B2
- Application number: 17/285,916
- Filed: 2019-10-24
- Published: 2021-11-18
- Granted: 2025-02-04
- Earliest claimed: 2018-10-29
- Assignees: Boehringer Ingelheim International GmbH
- Applicants: Boehringer Ingelheim International GmbH
- Inventors: Joerg P. Hehn; Andreas Blum; Oliver Hucke; Stefan Peters
- Web page: https://patentgrep.com/patent/US12213970B2

## CPC

- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/4427: containing further heterocyclic ring systems
- A61K 31/4545: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/12: of the kidneys
- A61P 27/00: Drugs for disorders of the senses
- A61P 35/00: Antineoplastic agents
- C07D 213/71: to which a second hetero atom is attached
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 401/14: containing three or more hetero rings
- C07D 405/14: containing three or more hetero rings
- 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
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The invention relates to new pyridinyl sulfonamide derivatives of the formula wherein R1, A and n are as defined herein, to their use as medicaments, to methods for their therapeutic use and to pharmaceutical compositions containing them.

## Claims

### Claim 1

A compound of formula (I)
wherein
ring A is selected from the group consisting of:
R1 is selected from the group consisting of H, F, Cl, Br, CN, —OH, C1-4-alkyl, —O—(C1-4-alkyl), —(CH2)m—COOH, —(CH2)m—C(═O)—O—(C1-4-alkyl), —(CH2)m—C(═O)-heterocyclyl, —(CH2)m—C(═O)—NH2, —(CH2)m—C(═O)—NH—(C1-4-alkyl), —(CH2)m—C(═O)—N(C1-4-alkyl)2, —C(═O)—NH—C3-6-cycloalkyl, —C(═O)—NH-heterocyclyl, (CH2)m—NH—C(═O)—(C1-3-alkyl), —N(C1-3-alkyl)-C(═O)—(C1-4-alkyl), —N(C1-3-alkyl)-C(═O)—NH2, —NH—C(═O)—NH—(C1-4-alkyl), heterocyclyl and phenyl,
wherein each alkyl group or sub-group is optionally substituted with 1 or more F atoms or with one OH or —O—(C1-3-alkyl) group; and
wherein each heterocyclyl is selected from the group consisting of azetidinyl, imidazolidinyl, piperidinyl, tetrahydropyranyl, morpholinyl, and each heterocyclyl is optionally substituted with one or two groups independently selected from the group consisting of OH, oxo, C1-3-alkyl, —C(═O)—CH3 and —C(═O)-cyclopropyl group;
wherein multiple R1 may be identical or different, if n is 2; and
n is an integer selected from 1 and 2; and
m is an integer selected from 0, 1 and 2; and
wherein in any definition mentioned hereinbefore, if not specified otherwise, any alkyl group or sub-group may be straight-chained or branched and is optionally substituted with 1 or more F atoms,
or a salt thereof.

### Claim 2 (depends on 1)

The compound of formula (I) according to claim 1, wherein
R1 is selected from the group consisting of:
H, F, —OH, C1-2-alkyl, —O—(C1-2-alkyl), —(CH2)m—COOH, —(CH2)m—C(═O)—O—(C1-2-alkyl), —(CH2)m—C(═O)-heterocyclyl, —(CH2)m—C(═O)—NH2, —(CH2)m—C(═O)—NH—(C1-4-alkyl), —(CH2)m—C(═O)—N(C1-2-alkyl)2, —C(═O)—NH-cyclo-propyl, —C(═O)—NH-heterocyclyl, —(CH2)m—NH—C(═O)—(C1-2-alkyl) and -heterocyclyl,
wherein each alkyl group or sub-group is optionally substituted with 1 or more F atoms or with one OH or —O—(C1-2-alkyl) group; and
wherein each heterocyclyl is selected from the group consisting of azetidinyl, imidazolidinyl, piperidinyl, tetrahydropyranyl, morpholinyl, and each heterocyclyl is optionally substituted with one or two groups independently selected from the group consisting of OH, oxo, C1-2-alkyl, —C(═O)—CH3 and —C(═O)-cyclopropyl;
wherein m is 0 or 1; and
wherein multiple R1 may be identical or different, if n is 2;
or a salt thereof.

### Claim 3 (depends on 2)

The compound of formula (I) according to claim 2, wherein
R1 is selected from the group consisting of:
H, —OH, —CH3, CF3, —O—CH3, —(CH2)m—COOH, —(CH2)m—C(═O)—O—(CH3), (CH2)m—C(═O)-heterocyclyl, —(CH2)m—C(═O)—NH2, —C(═O)—NH—(C1-4-alkyl), —C(═O)—N(CH3)2, —C(═O)—NH-cyclopropyl, —C(═O)—NH-tetrahydropyranyl, —(CH2)m—NH—C(═O)—(C1-2-alkyl) and 3-methyl-2-oxo-imidazolidin-1-yl,
wherein each alkyl group or sub-group is optionally substituted with 1 to 3 F atoms or with one OH or —O—CH3 group;
wherein each heterocyclyl is selected from the group consisting of azetidinyl and morpholinyl, and each heterocyclyl is optionally substituted with one OH group;
wherein m is 0 or 1; and
wherein if n is 2, multiple R1 may be identical or different, and the second R1 group is selected from the group consisting of CH3 and CF3;
or a salt thereof.

### Claim 4 (depends on 1)

The compound of formula (I) according to claim 1, wherein
ring A is
R1 is selected from the group consisting of H, F, —OH, C1-4-alkyl, —O—(C1-3-alkyl), —C(═O)—NH2, —C(═O)—NH—(C1-4-alkyl), —C(═O)—N(C1-4-alkyl)2 and heterocyclyl,
wherein each alkyl group or sub-group is optionally substituted with 1 or more F atoms or with one OH or —O—(C1-3-alkyl) group;
wherein each heterocyclyl is selected from the group consisting of azetidinyl, and piperidinyl, and each heterocyclyl is optionally substituted with one C1-3-alkyl, —C(═O)—CH3 or —C(═O)-cyclopropyl group; and
wherein, if n is 2, multiple R1 may be identical or different, and the second R1 group is CH3; and
n is an integer selected from 1 and 2;
or a salt thereof.

### Claim 5 (depends on 1)

The compound of formula (I) according to claim 1, wherein
ring A is
R1 is selected from the group consisting of H, F, —OH, —O—(C1-2-alkyl), —C(═O)-heterocyclyl, —(CH2)m—C(═O)—NH2, —(CH2)m—C(═O)—NH—(C1-4-alkyl), —(CH2)m—C(═O)—N(C1-4-alkyl)2, —(CH2)m—NH—C(═O)—(C1-3-alkyl) and —N(C1-3-alkyl)-C(═O)—(C1-4-alkyl),
wherein each alkyl group or sub-group is optionally substituted with 1 or more F atoms or with one OH or —O—(C1-3-alkyl) group; and
wherein each heterocyclyl is selected from the group consisting of azetidinyl, imidazolidinyl, piperidinyl, tetrahydropyranyl and morpholinyl, and each heterocyclyl is optionally substituted with one CH3 group;
n is 1; and
m is an integer selected from 0 and 1;
or a salt thereof.

### Claim 6 (depends on 1)

The compound of formula (I) according to claim 1, wherein
ring A is
R1 is selected from the group consisting of H, —(CH2)m—COOH, —(CH2)m—C(═O)—O—(C1-3-alkyl), —C(═O)-heterocyclyl, —(CH2)m—C(═O)—NH2, —(CH2)m—C(═O)—NH—(C1-3-alkyl) and —(CH2)m—C(═O)—N(C1-3-alkyl)2,
wherein each alkyl group or sub-group is optionally substituted with 1 or more F atoms or with one OH or —O—CH3 group; and
wherein each heterocyclyl is selected from the group consisting of azetidinyl, piperidinyl, tetrahydropyranyl and morpholinyl, and each heterocyclyl is optionally substituted with one CH3 group;
n is 1; and
m is an integer selected from 0 and 1;
or a salt thereof.

### Claim 7 (depends on 1)

The compound of formula (I) according to claim 1, wherein
ring A is
R1 is selected from the group consisting of H, —OH, C1-2-alkyl, —O—(C1-2-alkyl), —(CH2)m—COOH, —(CH2)m—C(═O)—O—(C1-2-alkyl), —(CH2)m—C(═O)-heterocyclyl, —(CH2)m—C(═O)—NH2, —(CH2)m—C(═O)—NH—(C1-4-alkyl), —(CH2)m—C(═O)—N(C1-2-alkyl)2, —C(═O)—NH-cyclopropyl, —C(═O)—NH-heterocyclyl, —(CH2)m—NH—C(═O)—(C1-2-alkyl), and heterocyclyl,
wherein each alkyl group or sub-group is optionally substituted with 1 or more F atoms or with one OH or —O—CH3 group;
wherein each heterocyclyl is selected from the group consisting of azetidinyl, imidazolidinyl, tetrahydropyranyl and morpholinyl, and each heterocyclyl is optionally substituted with one or two groups independently selected from the group consisting of OH, oxo, C1-2-alkyl and —C(═O)—CH3; and
wherein multiple R1 may be identical or different, if n is 2;
n is an integer selected from 1 and 2; and
m is an integer selected from 0 and 1;
or a salt thereof.

### Claim 8 (depends on 7)

The compound of formula (I) according to claim 7, wherein
R1 is selected from the group consisting of:
H, —OH, CH3, —O—CH3, —(CH2)m—COOH, —(CH2)m—C(═O)—O—CH3, —(CH2)m—C(═O)-heterocyclyl, —(CH2)m—C(═O)—NH2, —(CH2)m—C(═O)—NH—(C1-3-alkyl), —(CH2)m—C(═O)—N(CH3)2, —C(═O)—NH-cyclopropyl, —C(═O)—NH-heterocyclyl, —(CH2)m—NH—C(═O)—CH3 and -heterocyclyl,
wherein each alkyl group or sub-group is optionally substituted with 1 to 3 F atoms or with one OH or —O—CH3 group;
wherein each heterocyclyl is selected from the group consisting of azetidinyl, imidazolidinyl and tetrahydropyranyl, and each heterocyclyl is optionally substituted with one or two groups independently selected from the group consisting of OH, oxo, CH3 and —C(═O)—CH3,
wherein m is 0 or 1; and
wherein, if n is 2, multiple R1 may be identical or different and the second R1 group is selected from the group consisting of CH3 and CF3;
or a salt thereof.

### Claim 9 (depends on 1)

The compound of formula (I) according to claim 1 selected from the group consisting of:
or a salt thereof.

### Claim 10 (depends on 1)

A pharmaceutically acceptable salt of a compound according to claim 1.

### Claim 11 (depends on 1)

A method for treating melanoma, lymphoma, NASH (non-alcoholic steatohepatitis), pulmonary fibrosis, retinopathy, nephropathy or stroke, comprising administering a pharmaceutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, to a patient in need thereof.

### Claim 12 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1, or a pharmaceutically acceptable salt thereof, optionally together with one or more inert carriers and/or diluents.

### Claim 13 (depends on 1)

A method for treating a disease or condition which is mediated by inhibiting the activity of AOC3, comprising administering a pharmaceutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, to a patient in need thereof.

### Claim 14 (depends on 1)

A pharmaceutical composition comprising one or more compounds according to claim 1, or a pharmaceutically acceptable salt thereof, and one or more additional therapeutic agents, optionally together with one or more inert carriers and/or diluents.

### Claim 15 (depends on 13)

The method according to claim 13, wherein the disease or condition is selected from the group consisting of inflammatory diseases, eczema, pain, inflammatory bowel disease, multiple sclerosis, scleroderma, pulmonary diseases, nephropathy, diabetic proteinuria, kidney fibrosis, diabetic retinopathy, diabetic oedema, cancer, hepatocellular carcinoma, unspecified Colitis, rheumatoid Crohn's disease Colitis, biliary tract diseases, primary biliary cholangitis, primary sclerosing cholangitis, non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, liver fibrosis, liver cirrhosis, ulcerative reperfusion injury, cerebral ischaemia, and transplant rejection.

### Claim 16 (depends on 13)

The method according to claim 13, wherein the disease or condition is selected from the group consisting of vascular inflammatory diseases, arthritis, acute joint inflammation, chronic joint inflammation, atopic eczema, psoriasis ulcerative and rheumatoid psoriasis, musculoskeletal or nociceptive pain, non-infectious inflammatory bowel disease, respiratory distress syndrome, asthma, pulmonary fibrosis, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), idiopathic inflammatory disease, macular diabetic oedema, melanoma, and lymphoma.