# US 10,479,771 B2 · Pyridazinone and pyridone compounds

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- Number: US 10,479,771 B2
- Document ID: US10479771B2
- Status: Granted
- Kind: B2
- Application number: 15/729,735
- Filed: 2017-10-11
- Published: 2018-02-01
- Granted: 2019-11-19
- Earliest claimed: 2011-03-08
- Assignees: Biotie Therapies, Inc.
- Applicants: Biotie Therapies Corporation
- Inventors: Marjo Pihlavisto; David Smith; Auni Juhakoski; Ferenc Fulop; Laszlo Lazar; Istvan Szatmari; Ferenc Miklos; Zsolt Szakonyi; Lorand Kiss; Marta Palko
- Web page: https://patentgrep.com/patent/US10479771B2

## CPC

- C07D 237/24: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/50: Pyridazines; Hydrogenated pyridazines
- A61K 31/501: not condensed and containing further heterocyclic rings
- 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 11/00: Drugs for disorders of the respiratory system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/02: Immunomodulators
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07C 57/15: Fumaric acid
- C07D 237/16: Two oxygen atoms
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/14: containing three or more hetero rings
- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 403/14: containing three or more hetero rings
- C07D 405/04: directly linked by a ring-member-to-ring-member bond
- C07D 405/14: containing three or more hetero rings
- C07D 409/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- G01N 33/502: {for testing non-proliferative effects}
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The invention relates to pyridazinone and pyridone compounds having formula (I) or (I′), and pharmaceutically acceptable salts, hydrates, and solvates thereof wherein R1/R4 and X and X3 are as defined in the claims. The invention further relates to their use as inhibitors of copper-containing amine oxidases. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds, pharmaceutically acceptable salts, hydrates, or solvates thereof.

## Claims

### Claim 1

A method for treating a SSAO/VAP-1 related disease comprising administering to a patient in need thereof an effective amount of a composition comprising a compound of general formula (I′), or pharmaceutically acceptable salt, hydrate, or solvate thereof,
wherein
X is CH;
R1 is phenyl, optionally substituted with R11,
wherein R11 is selected from the group consisting of halogen, halo-C1-3-alkyl, and C1-6-alkoxy;
R2 is H or triazolyl;
(i) X3 is O or S, and
R3 is selected from the group consisting of H, C1-6-alkyl, C2-6-alkenyl, and phenyl, said phenyl being optionally substituted one or more times with R31, each R31 is independently selected from the group consisting of halogen, halo-C1-3-alkyl and C1-6-alkoxy; or
(ii) X3 is NR3′, and
R3 and R3′ together with the nitrogen, to which they are attached, form a 5 or 6 membered saturated heterocyclic ring, —N3, or triazole, said triazole being optionally substituted with R32, wherein R32 is selected from the group consisting of phenyl, C1-6-alkyl, and —CO2(C1-3-alkyl); or
R3′ is H or C1-3-alkyl, and
R3 is selected from the group consisting of H; C1-6-alkyl; C2-6-alkenyl; C2-6-alkynyl; C3-6-cycloalkyl-C1-6-alkyl; C3-6-cycloalkyl; cyano-C1-6-alkyl; amino-C1-6-alkyl; benzyl; pyridyl; saturated 5 or 6 membered heterocyclic ring having 1 to 2 heteroatoms selected from N, O, and S, and wherein said N is optionally substituted with C1-6-alkyl; R33R33′N—C1-6-alkylenyl; and phenyl, said phenyl being optionally substituted 1 to 3 times with R34;
wherein
R33 and R33′ are both C1-3-alkyl, or R33 and R33′ together with the nitrogen, to which they are attached, form a saturated 5 or 6 membered heterocyclic ring optionally comprising one further heteroatom selected from N, O, and S;
each R34 is independently selected from the group consisting of NR35R35′, hydroxy and C1-6-alkoxy; or two adjacent R34 together with the carbon atoms, to which they are attached, form a 5 or 6 membered fused heterocyclic ring comprising 1 or 2 heteroatom(s) each independently selected from N, O and S;
wherein R35 and R35′ are both H or C1-6-alkyl; or R35 and R35′ together with the nitrogen, to which they are attached, form a 5 or 6 membered saturated heterocyclic ring optionally further comprising as a ring member O, S, N, or NR36, wherein R36 is H, C1-6-alkyl or benzoyl;
R4 is selected from the group consisting of —CN; —C(═O)X4R41; phenyl, wherein said phenyl is optionally substituted with R42; and an 5 or 6 membered unsaturated heterocyclic ring having 1 to 4 heteroatoms each independently selected from N, O and S and being optionally substituted one or more times with R43;
wherein X4 is 0, S, or NH; and
R41 is selected from the group consisting of H, C1-6-alkyl, R44R44′N—C1-6-alkylenyl, and —NHR45,
wherein R44 and R44′ are both H or C1,6-alkyl; or R44 and R44′ together with the nitrogen, to which they are attached, form a 5 or 6 membered saturated heterocyclic ring; and
R45 is H or imino-C1-6alkyl; or
X4 and R41 taken together form —N═CR46R47, wherein
R46 is H or methyl, and
R47 is di(C1-3-alkyl)amino;
R42 is selected from the group consisting of halogen, halo-C1-3-alkyl, and C1-6-alkoxy;
each R43 is independently selected from the group consisting of OH, SH, and methyl, and
wherein the SSAO/VAP-1 related disease is selected from the group consisting of diabetic kidney disease, renal fibrosis, neointimal and medial fibrosis, vascular stenosis, restenosis, arterial fibrosis, arthrofibrosis, liver fibrosis, arthritis, multiple sclerosis and lung inflammation.

### Claim 2 (depends on 1)

The method of claim 1, wherein the disease is selected from the group consisting of inflammation, a disease caused by inflammation, a disease which causes inflammation, an immune disorder, an autoimmune disorder, and a fibrotic condition.

### Claim 3 (depends on 2)

The method of claim 2, wherein the disease is inflammation, a disease caused by inflammation, or a disease which causes inflammation.

### Claim 4 (depends on 2)

The method of claim 2, wherein the disease is an immune disorder or autoimmune disorder.

### Claim 5 (depends on 2)

The method of claim 2, wherein the disease is a fibrotic condition.