# US 2013/0158038 A1 · Novel compounds

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

- Number: US 2013/0158038 A1
- Document ID: US20130158038A1
- Status: Published application
- Kind: A1
- Application number: 13/709,319
- Filed: 2012-12-10
- Published: 2013-06-20
- Earliest claimed: 2011-12-14
- Assignees: Boehringer Ingelheim International GmbH
- Inventors: Klaus RUDOLF; Daniel BISCHOFF; Georg DAHMANN; Matthias GRAUERT; Raimund KUELZER
- Web page: https://patentgrep.com/patent/US20130158038A1

## CPC

- C07D 403/14: containing three or more hetero rings
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- 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 25/30: for treating abuse or dependence
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 233/64: with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 401/14: containing three or more hetero rings
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention relates to compounds of formula I their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, Ar, R1, R2, R3 have meanings given in the description.

## Claims

### Claim 1

A compound of formula I
in which
A and B independently represent CH or N;
R1 represents aryl, heteroaryl, C1-8alkyl, C3-7cycloalkyl or —O—C1-8alkyl which latter five groups are optionally substituted with one or more substituents selected from halogen, —CN, C1-3alkyl and —O—C1-3 alkyl;
R2 and R3 independently represent —H, halogen, —CN, C1-5alkyl, C3-5cycloalkyl or —O—C1-5alkyl which latter three groups are optionally substituted with one or more fluorine atoms;
Ar represents
R4 and R5 independently represent —H, halogen, —OH, —CN, —NH2, C1-5alkyl, phenyl, —NH—C1-5alkyl, —N(C1-5 alkyl)2, —O—C1-5alkyl, —COO—C1-5alkyl, —CONH(C1-5alkyl), —CON(C1-5alkyl)2, —NHCONH—C1-5alkyl, —NHCON(C1-5alkyl)2 or —NHCO—C1-5alkyl which latter eleven groups are optionally substituted with one or more substituents selected from halogen and —OH;
or a physiologically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein
R1 represents phenyl or C1-4alkyl which latter two groups are optionally substituted with one or more substituents selected from fluoro, C1-3alkyl and —O—C1-3alkyl.

### Claim 3 (depends on 2)

The compound according to claim 2, wherein the group
represents
phenyl optionally substituted with one or more substituents selected from chloro, fluoro, C1-3alkyl and —O—C1-3alkyl, which latter two groups are optionally substituted with one or more fluorine atoms.

### Claim 4

A compound of the formula I
in which
R1 represents phenyl or C1-4alkyl which latter two groups are optionally substituted with one or more substituents selected from fluoro, C1-3alkyl and —O—C1-3alkyl;
Ar represents pyridinyl, pyridazinyl, pyrimidinyl or triazinyl which latter four groups are optionally substituted with one or more substituents selected from fluoro, C1-3alkyl and —O—C1-3alkyl which latter two groups are optionally substituted with one or more fluorine atoms;
the group
represents
phenyl optionally substituted with one or more substituents selected from chloro, fluoro, C1-3alkyl and —O—C1-3alkyl, which latter two groups are optionally substituted with one or more fluorine atoms;
or a physiologically acceptable salt thereof.

### Claim 5 (depends on 1)

The compound according to claim 1, wherein
Ar represents phenyl,
which latter six groups are optionally substituted with one or more substituents selected from fluoro, C1-3alkyl and O—C1-3alkyl which latter two groups are optionally substituted with one or more fluorine atoms.

### Claim 6 (depends on 5)

The compound according to claim 5, wherein
R1 represents ethyl, phenyl,

### Claim 7 (depends on 6)

The compound according to claim 6, wherein
Ar represents

### Claim 8 (depends on 7)

The compound according to claim 7, wherein
the group

### Claim 9

A compound of formula I
in which
R1 represents ethyl, phenyl,
Ar represents
the group
or a physiologically acceptable salt thereof.

### Claim 10

A compound selected from the group consisting of
or a
physiologically acceptable salt thereof.

### Claim 11 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable adjuvant, diluent and/or carrier.

### Claim 12 (depends on 1)

A method of treating schizophrenia, schizoaffective disorder and substance induced psychotic disorder; cognitive disorders and dementias including age-associated learning and memory impairments or losses, post stroke dementia, deficits in concentration, mild cognitive impairment, the cognitive dysfunction in Alzheimers disease or the cognitive dysfunction of schizophrenia comprising administering to a patient a therapeutically effective amount of a compound according to claim 1.