# US 7,608,633 B2 · Heteroaryl-substituted acetone derivatives as inhibitors of phospholipase A2

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

- Number: US 7,608,633 B2
- Document ID: US7608633B2
- Status: Granted
- Kind: B2
- Application number: 10/544,300
- Filed: 2004-02-06
- Published: 2006-06-29
- Granted: 2009-10-27
- Earliest claimed: 2003-02-07
- Assignees: Merckle GmbH
- Inventors: Matthias Lehr; Joachim Ludwig
- Web page: https://patentgrep.com/patent/US7608633B2

## CPC

- C07D 249/08: 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- 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 11/06: Antiasthmatics
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/04: Antipruritics
- A61P 17/06: Antipsoriatics
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 207/325: with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
- C07D 207/34: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D 209/08: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
- C07D 209/12: Radicals substituted by oxygen atoms
- C07D 209/42: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 231/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 231/56: Benzopyrazoles; Hydrogenated benzopyrazoles
- C07D 233/56: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The invention relates to novel heteroaryl substituted acetone derivatives which inhibit the enzyme phospholipase A2, pharmaceutical preparations containing these compounds and a method of producing these compounds.

## Claims

### Claim 1

A compound of formula I
wherein
Q represents R1, OR1, SR1, SOR1, SO2R1, NR9R1 or a straight-chain C1-31 alkyl or C2-31 alkenyl or alkinyl group which is optionally interrupted by 1 or 2 groups, independently selected from O, S, SO, SO2, NR9 and aryl which are optionally substituted with 1 or 2 substituents R4, and which are optionally substituted with 1-4 C1-6 alkyl groups and/or 1 or 2 aryl groups, wherein the aryl groups is optionally substituted with 1 or 2 substituents R4;
Ar represents an aryl group selected from the group consisting of a phenyl, naphthyl, biphenyl, and 5-membered heterocylic ring and 6-membered heterocyclic ring, said aryl group containing 1 to 3 atoms selected from O, N, or S and optionally annellated using a benzene ring and further which is optionally substituted with 1 or 2 substituents R4;
X represents N or CR5;
Y represents N or CR6;
R1 represents H or an aryl group which is optionally substituted with 1 or 2 substituents R4;
R2 and R3 a) independently stand for H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl or R7—W, or b) together with the carbon atoms to which they are bound, form a 5- or 6-membered aromatic or heteroaromatic ring which is optionally substituted with 1 or 2 substituents R4;
R4 represents C1-6 alkyl, halogen, CF3, CN, NO2, OR9, S(O)0R9, COR9, COOR9, CONR9R10, SO3R9, SO2NR9R10, tetrazolyl or R7—W
R5 represents H or R4;
R6 represents H, C1-6 alkyl, halogen, CF3, CN, NO2, OR9, S(O)0R9, COR9, COOR9, CONR9R10, SO3R9, SO2NR9R10, tetrazolyl or R8—W;
R7 represents C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl;
R8 represents C2-6 alkyl, C2-6 alkenyl or C2-6 alkynyl;
R9 represents H, C1-6 alkyl or aryl;
R10 represents H or C1-6 alkyl;
W represents COOH, SO3H or tetrazolyl; and
o represents 0, 1 or 2;
and the pharmaceutically compatible salts and esters thereof.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein Q represents
R1—(CHR11)p—A—Z2—B—Z1—
wherein
A represents a bond or a straight-chain C1-m alkyl residue or C2-m alkenyl or alkinyl group;
B represents a bond or a straight chain C1-n alkyl residue or C2-n alkenyl or alkynyl group;
R11 represents H or an aryl group which is optionally substituted with 1 or 2 substituents R4;
Z1 and Z2 independently represent a bond, O, S, SO, SO2, NR9, CR9R10 or an aryl group, wherein the aryl group is optionally substituted with 1 or 2 substituents R4;
R1, R4, R9 and R10 are as defined in claim 1;
p represents 0 or 1;
m represents an integer from 0 to 12; and
n represents an integer from 0 to 16.

### Claim 3 (depends on 2)

The compound according to claim 2, wherein m+n≦17.

### Claim 4 (depends on 2)

The compound according to claim 2, wherein Q is selected from the group consisting of:
R1—B—Z1—
R1—CHR11—B—Z1—
R1—A—Z2—B—Z1— and
R1—CHR11—A—Z2—B—Z1—,
Wherein A, B, R1, R11, Z1, Z2, n and m are as defined in claim 2.

### Claim 5 (depends on 4)

The compound according to claim 4, wherein Q represents phenyl or C5-12 alkyl or alkoxy.

### Claim 6 (depends on 1)

The compound according to claim 1, wherein Ar represents a phenyl or indolyl group.

### Claim 7 (depends on 1)

The compound according to claim 1, wherein R2 and R3
a) independently represent H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl or R7—W or
b) together with the carbon atoms to which they are bound form a benzo ring or a 6-membered aromatic heterocyclic ring having 1-3 nitrogen atoms, wherein the benzo ring or the heterocyclic ring is optionally substituted with 1 or 2 substituents R4, and R4 is defined as in claim 1.

### Claim 8 (depends on 7)

The compound according to claim 7, wherein R2 and R3 represent H or together with the carbon atoms to which they are bound form a benzo ring which is optionally substituted with a substituent R4.

### Claim 9 (depends on 1)

The compound according to claim 1, wherein X═CR5 and Y═CR6 or X═N and Y═CR6, wherein R5 and R6 are as defined in claim 1.

### Claim 10 (depends on 1)

A pharmaceutical preparation comprising a compound of general formula I according to claim 1 or a pharmaceutically compatible salt or ester thereof.

### Claim 11 (depends on 1)

A method of producing a compound of formula I according to claim 1, wherein a compound of formula II
or a compound of formula III
is reacted with a compound of formula IV
and the alcohol formed is oxidized into the desired ketone, wherein Q, Ar, X, Y, R2 and R3 are as defined in claim 1 and Abg represents a leaving group.

### Claim 12 (depends on 3)

The compound according to claim 3, wherein Q is selected from
R1—B—Z1—
R1—CHR11—B—Z1—
R1—A—Z2—B—Z1— and
R1—CHR11—A—Z2—B—Z1—.

### Claim 13 (depends on 4)

The compound according to claim 4, wherein Q represents phenyl or C5-12 alkyl or alkoxy.

### Claim 14 (depends on 5)

The compound according to claim 5, wherein Q represents C7-10 alkyl or alkoxy.

### Claim 15 (depends on 8)

The compound according to claim 8, wherein substituent R4 is selected from the group consisting of COOH, CH3, Cl, OCH3, CN, CHO, COOCH3 and CONH2.

### Claim 16 (depends on 9)

The compound according to claim 9, wherein R5 and R6 are independently selected from the group consisting of H, COOH, t-butyl, Cl, CHO, COCH3 and COOCH3.

### Claim 17 (depends on 13)

The compound according to claim 13, wherein Q represents C7-10 alkyl or alkoxy.

### Claim 18 (depends on 11)

The method according to claim 11, wherein the leaving group is a halogen.