# US 12,006,303 B2 · Substituted indazoles, methods for the production thereof, pharmaceutical preparations that contain said substituted indazoles, and use of said substituted indazoles to produce drugs

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- Number: US 12,006,303 B2
- Document ID: US12006303B2
- Status: Granted
- Kind: B2
- Application number: 17/869,673
- Filed: 2022-07-20
- Published: 2023-06-08
- Granted: 2024-06-11
- Earliest claimed: 2014-11-26
- Assignees: Bayer Pharma Aktiengesellschaft
- Applicants: Bayer Pharma Aktiengesellschaft
- Inventors: Ulrich Bothe; Holger Siebeneicher; Nicole Schmidt; Reinhard Nubbemeyer; Ulf Bömer; Judith Günther; Holger Steuber; Martin Lange; Christian Stegmann; Andreas Sutter; Alexandra Rausch; Christian Friedrich; Peter Hauff
- Web page: https://patentgrep.com/patent/US12006303B2

## CPC

- C07D 401/12: linked by a chain containing hetero atoms as chain links
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 17/00: Drugs for dermatological disorders
- 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 35/00: Antineoplastic agents
- C07D 405/14: containing three or more hetero rings
- C07F 7/1804: {Compounds having Si-O-C linkages (Si-O-acyl linkages C07F7/1896)}
- 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
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

The present application relates to novel substituted indazoles, to processes for preparation thereof, to the use thereof alone or in combinations for treatment and/or prophylaxis of diseases, and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially for treatment and/or prophylaxis of endometriosis and endometriosis-associated pain and other endometriosis-associated symptoms such as dysmenorrhoea, dyspareunia, dysuria and dyschezia, of lymphoma, rheumatoid arthritis, spondyloarthritis (especially psoriatic spondyloarthritis and Bekhterev's disease), lupus erythematosus, multiple sclerosis, macular degeneration, COPD, gout, fatty liver disorders, insulin resistance, neoplastic disorders and psoriasis.

## Claims

### Claim 1

A method for treating a dermatological disease or disorder in a human in need thereof, comprising administering to the human an effective amount of a compound of formula (I):
wherein:
R1 is C1-C6-alkyl, wherein the C1-C6-alkyl group is monosubstituted with an R7SO2 or R7SO2 group, or
wherein the C1-C6-alkyl group is polysubstituted with at least one of an R7SO2 group or R7SO group, and one or more additional substituents selected from the group consisting of halogen, hydroxyl, an unsubstituted or mono- or poly-halogen substituted C3-C6-cycloalkyl, an R6 group, and an R8O group;
R2 and R3 always have the same definition and are both either hydrogen or C1-C6-alkyl;
R4 is halogen, cyano, an unsubstituted or a singly or multiply, identically or differently substituted C1-C6-alkyl or an unsubstituted or a singly or multiply, identically or differently substituted C3-C6-cycloalkyl, and the substituents are selected from the group consisting of halogen and hydroxyl;
R5 is hydrogen, halogen or an unsubstituted or mono- or poly-halogen-substituted C1-C6-alkyl;
R6 is an unsubstituted or mono- or di-methyl-substituted monocyclic saturated heterocycle having 4 to 6 ring atoms, which contains a heteroatom or a heterogroup from the group of O, S, SO and SO2;
R7 is C1-C6-alkyl, where the C1-C6-alkyl group is unsubstituted or mono- or polysubstituted identically or differently by halogen, hydroxyl or C3-C6-cycloalkyl;
or R7 is C3-C6-cycloalkyl; and
R8 is C1-C6-alkyl, where the C1-C6-alkyl group is unsubstituted or mono- or polysubstituted identically or differently by halogen,
or a diastereomer, an enantiomer, a salt, a solvate, or a solvate of the salt thereof.

### Claim 2 (depends on 1)

The method according to claim 1, wherein:
R1 is C1-C6-alkyl, wherein the C1-C6-alkyl group is monosubstituted with an R7SO2 group or an R7SO group, or
wherein the C1-C6-alkyl group is polysubstituted with at least one of an R7SO2 group or an R7SO group, and one or more additional substituents selected from the group consisting of fluorine, hydroxyl, an R6 group, and an R8O group;
R2 and R3 always have the same definition and are both either hydrogen or C1-C3-alkyl;
R4 is halogen, cyano or C1-C3-alkyl, wherein the C1-C3-alkyl group is unsubstituted or mono- or polysubstituted identically or differently by halogen or hydroxyl;
R5 is hydrogen, fluorine, chlorine or C1-C3-alkyl;
R6 is oxetanyl or tetrahydrofuranyl;
R7 is C1-C4-alkyl, wherein the C1-C4-alkyl group is unsubstituted or monosubstituted by hydroxyl or by cyclopropyl or substituted by three fluorine atoms, and
R8 is an unsubstituted C1-C4-alkyl group or a tri-fluorine-substituted C1-C4-alkyl group.

### Claim 3 (depends on 1)

The method according to claim 1, wherein R4 is difluoromethyl, trifluoromethyl or methyl.

### Claim 4 (depends on 1)

The method according to claim 1, wherein R5 is hydrogen or fluorine.

### Claim 5 (depends on 1)

The method according to claim 1, wherein R2 and R3 are both either hydrogen or methyl.

### Claim 6 (depends on 2)

The method according to claim 2, wherein
R1 is C2-C6-alkyl, wherein the C2-C6-alkyl group is monosubstituted by an R7SO2 group;
R2 and R3 always have the same definition and are both either hydrogen or methyl;
R4 is an unsubstituted or mono- or poly-halogen-substituted C1-C3-alkyl group or a C1-C3-alkyl group substituted by one hydroxyl group or a C1-C3-alkyl group substituted by one hydroxyl group and three fluorine atoms;
R5 is hydrogen, fluorine or C1-C3-alkyl, and
R7 is C1-C3-alkyl.

### Claim 7 (depends on 6)

The method according to claim 6, wherein
R1 is a methyl-SO2-substituted C2-C4-alkyl group;
R2 and R3 always have the same definition and are both either hydrogen or methyl;
R4 is selected from the group consisting of methyl, ethyl, trifluoro-C1-C3-alkyl, difluoro-C1-C3-alkyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxypropan-2-yl and 2,2,2-trifluoro-1-hydroxyethyl, and
R5 is hydrogen, fluorine or methyl.

### Claim 8 (depends on 7)

The method according to claim 7, wherein
R1 is 2-(methyl sulphonyl)ethyl or 3-(methylsulphonyl)propyl;
R2 and R3 are both either methyl or hydrogen;
R4 is difluoromethyl, trifluoromethyl or methyl; and
R5 is hydrogen or fluorine.

### Claim 9 (depends on 8)

The method according to claim 8, wherein
R1 is 3-(methylsulphonyl)propyl or 2-(methylsulphonyl)ethyl;
R2 and R3 re both methyl;
R4 is difluoromethyl or trifluoromethyl; and
R5 is hydrogen.

### Claim 10 (depends on 8)

The method according to claim 8, wherein
R1 is 3-(methylsulphonyl)propyl or 2-(methyl sulphonyl)ethyl;
R2 and R3 re both methyl;
R4 is methyl; and
R5 is fluorine, wherein R5 is in the ortho position to R4.

### Claim 11 (depends on 1)

The method according to claim 1, wherein the compound is:
or a metabolite, a salt, a solvate, a solvate of the salt thereof.

### Claim 12 (depends on 1)

The method according to claim 1, wherein the compound is:
or a salt thereof.

### Claim 13 (depends on 1)

The method according to claim 1, wherein the dermatological disease or disorder is psoriasis, atopic dermatitis, Kindler's syndrome, bullous pemphigoid, allergic contact dermatitis, alopecia areata, acne inversa or acne vulgaris.

### Claim 14 (depends on 1)

The method according to claim 1, wherein the dermatological disease or disorder is psoriasis, atopic dermatitis, allergic contact dermatitis, or acne inversa.

### Claim 15 (depends on 1)

The method according to claim 1, wherein the dermatological disease or disorder is atopic dermatitis.

### Claim 16 (depends on 11)

The method according to claim 11, wherein the dermatological disease or disorder is psoriasis, atopic dermatitis, Kindler's syndrome, bullous pemphigoid, allergic contact dermatitis, alopecia areata, acne inversa or acne vulgaris.

### Claim 17 (depends on 11)

The method according to claim 11, wherein the dermatological disease or disorder is psoriasis, atopic dermatitis, allergic contact dermatitis, or acne inversa.

### Claim 18 (depends on 11)

The method according to claim 11, wherein the dermatological disease or disorder is atopic dermatitis.

### Claim 19 (depends on 12)

The method according to claim 12, wherein the dermatological disease or disorder is psoriasis, atopic dermatitis, Kindler's syndrome, bullous pemphigoid, allergic contact dermatitis, alopecia areata, acne inversa or acne vulgaris.

### Claim 20 (depends on 12)

The method according to claim 12, wherein the dermatological disease or disorder is psoriasis, atopic dermatitis, allergic contact dermatitis, or acne inversa.

### Claim 21 (depends on 12)

The method according to claim 12, wherein the dermatological disease or disorder is atopic dermatitis.

### Claim 22 (depends on 1)

The method according to claim 1, wherein the compound is administered to the human in a dosage form comprising at least one pharmaceutically suitable excipient.

### Claim 23 (depends on 11)

The method according to claim 11, wherein the compound is administered to the human in a dosage form comprising at least one pharmaceutically suitable excipient.

### Claim 24 (depends on 12)

The method according to claim 12, wherein the compound is administered to the human in a dosage form comprising at least one pharmaceutically suitable excipient.