# US 10,370,344 B2 · 2-oxothiazole compounds and method of using same for chronic inflammatory disorders

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

- Number: US 10,370,344 B2
- Document ID: US10370344B2
- Status: Granted
- Kind: B2
- Application number: 15/442,568
- Filed: 2017-02-24
- Published: 2017-06-15
- Granted: 2019-08-06
- Earliest claimed: 2009-10-02
- Assignees: Avexxin AS
- Applicants: Avexxin AS
- Inventors: George Kokotos; Berit Johansen; Victoria Magrioti; Michael Tsakos
- Web page: https://patentgrep.com/patent/US10370344B2

## CPC

- C07D 277/64: with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
- A61K 31/421: 1,3-Oxazoles, e.g. pemoline, trimethadione
- A61K 31/423: condensed with carbocyclic rings
- A61K 31/426: 1,3-Thiazoles
- A61K 31/428: condensed with carbocyclic rings
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 17/06: Antipsoriatics
- A61P 17/08: Antiseborrheics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- C07D 277/24: Radicals substituted by oxygen atoms
- C07D 277/28: Radicals substituted by nitrogen atoms
- C07D 277/30: Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 277/56: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- 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

## Abstract

The invention provides compounds of formula (I) wherein X is O or S; R1 is H, OH, SH, nitro, NH2, NHC1-6alkyl, N(C1-6alkyl)2, halo, haloC1-6alkyl, CN, C1-6-alkyl, OC1-6alkyl, C1-6alkylCOOH, C1-6alkylCOOC1-6alkyl, C2-6-alkenyl, C3-10cycloalkyl, C6-10aryl, C1-6alkylC6-10aryl, heterocyclyl, heteroaryl, CONH2, CONHC1-6alkyl, CON(C1-6alkyl)2, OCOC1-6alkyl, or is an acidic group, such as a group comprising a carboxyl, phosphate, phosphinate, sulfate, sulfonate, or tetrazolyl group; R2 is as defined for R1 or R1 and R2 taken together can form a 6-membered aromatic ring optionally substituted by up to 4 groups R5; R3 is H, halo (preferably fluoro), or CHal3 (preferably CF3); each R5 is defined as for R1; V1 is a covalent bond, —O—, or a C1-20alkyl group, or C2-20-mono or multiply unsaturated alkenyl group; said alkyl or alkenyl groups being optionally interrupted by one or more heteroatoms selected from O, NH, N(C1-6 alkyl), S, SO, or SO2; M1 is absent or is a C5-10 cyclic group or a C5-15 aromatic group; and R4 is H, halo, OH, CN, nitro, NH2, NHC1-6alkyl, N(C1-6alkylh, haloC1-6alkyl, a C1-20alkyl group, or C2-20-mono or multiply unsaturated alkenyl group, said C1-20alkyl or C2-20oalkenyl groups being optionally interrupted by one or more heteroatoms selected from O, NH, N(C1-6 alkyl), S, SO, or SO2; with the proviso that the group V1M1R4 as a whole provides at least 4 backbone atoms from the C(R3) group; or a salt, ester, solvate, N-oxide, or prodrug thereof; for use in the treatment of a chronic inflammatory condition.

## Claims

### Claim 1

A method of treating a chronic inflammatory disorder mediated by phospholipase enzyme cPLA2 activity comprising administering to a patient in need thereof an effective amount of a compound of the following formula:
R2 is H, COOH, COOC1-6alkyl or C1-6alkylCOOH;
R3′ is C1-6 alkyl;
M1 is phenyl; and
R4 is H, haloC1-6alkyl, a linear C1-20alkyl group, C1-10 alkoxy, —SC1-20alkyl group or C2-20-mono or multiply unsaturated alkenyl group;
or a salt or solvate thereof.

### Claim 2 (depends on 1)

A method as claimed in claim 1 wherein R4 is a linear C1-20alkyl group or C1-10 alkoxy.

### Claim 3

A method of treating a chronic inflammatory disorder selected from the group consisting of glomerulonephritis, rheumatoid arthritis and psoriasis, comprising administering to a patient in need thereof an effective amount of a compound of the following formula:
R2 is H, COOH, COOC1-6alkyl or C1-6alkylCOOH;
R3′ is C1-6 alkyl;
M1 is phenyl; and
R4 is H, haloC1-6alkyl, a linear C1-20alkyl group, C1-10 alkoxy, —SC1-20alkyl group or C2-20-mono or multiply unsaturated alkenyl group;
or a salt or solvate thereof.

### Claim 4

A method of treating a chronic inflammatory disorder mediated by phospholipase enzyme cPLA2 activity comprising administering to a patient in need thereof an effective amount of a compound of the following formula:
R2 is H, COOC1-6alkyl or C1-6alkylCOOC1-6alkyl;
R3′ is H;
M1 is phenyl; and
R4 is H, a linear C1-20alkyl group, C1-10 alkoxy, —SC1-20alkyl group or C2-20-mono or multiply unsaturated alkenyl group;
or a salt or solvate thereof.

### Claim 5 (depends on 4)

A method as claimed in claim 4 wherein R4 is a linear C1-20alkyl group or C1-10 alkoxy.

### Claim 6

A method of treating a chronic inflammatory disorder selected from the group consisting of glomerulonephritis, rheumatoid arthritis and psoriasis, comprising administering to a patient in need thereof an effective amount of a compound of the following formula:
R2 is H, COOC1-6alkyl or C1-6alkylCOOC1-6alkyl;
R3′ is H;
M1 is phenyl; and
R4 is H, a linear C1-20alkyl group, C1-10 alkoxy, —SC1-20alkyl group or C2-20-mono or multiply unsaturated alkenyl group;
or a salt or solvate thereof.

### Claim 7 (depends on 1)

A method as claimed in claim 1 wherein R4 is a linear C1-20alkyl group or C1-10 alkoxy.

### Claim 8 (depends on 6)

A method as claimed in claim 6 wherein R4 is a linear C1-20alkyl group or C1-10 alkoxy.