# US 2008/0188490 A1 · Acetylene Derivatives

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- Number: US 2008/0188490 A1
- Document ID: US20080188490A1
- Status: Published application
- Kind: A1
- Application number: 11/912,624
- Filed: 2006-04-24
- Published: 2008-08-07
- Earliest claimed: 2005-04-25
- Inventors: Ralf Glatthar; Thomas J. Troxler
- Web page: https://patentgrep.com/patent/US20080188490A1

## CPC

- C07C 215/44: bound to carbon atoms of the same ring or condensed ring system
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/10: Laxatives
- A61P 1/12: Antidiarrhoeals
- A61P 3/02: Nutrients, e.g. vitamins, minerals
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 13/10: of the bladder
- A61P 17/00: Drugs for dermatological disorders
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/22: Anxiolytics
- A61P 25/24: Antidepressants
- 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 25/36: Opioid-abuse
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07C 49/747: containing six-membered aromatic rings
- C07D 213/74: Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
- C07D 215/40: attached in position 8
- C07D 231/38: Nitrogen atoms (nitro radicals C07D231/16)
- C07D 231/56: Benzopyrazoles; Hydrogenated benzopyrazoles
- C07D 233/64: with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
- C07D 235/06: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D 239/12: Nitrogen atoms not forming part of a nitro radical
- C07D 241/20: Nitrogen atoms (nitro radicals C07D241/16)
- C07D 241/42: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D 241/44: 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 carbon atoms of the hetero ring
- C07D 249/08: 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D 277/42: Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
- C07D 285/14: condensed with carbocyclic rings or ring systems
- C07D 405/04: directly linked by a ring-member-to-ring-member bond
- C07D 487/04: Ortho-condensed systems
- C07C 2601/14: The ring being saturated
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The invention provides compounds of formula (I) wherein the substituents are as defined in the specification, to processes for their preparation and corresponding intermediates, and their use as pharmaceuticals.

## Claims

### Claim 1

A compound of formula (I)
wherein
R1 represents hydrogen or C1-C4 alkyl and
R2 represents an unsubstituted or substituted heterocycle or
R1 represents hydrogen or C1-C4 alkyl and
R2 represents aryl or substituted aryl or
R1 and R2 together with the nitrogen atom form an unsubstituted or substituted heterocycle;
R3 represents (C1-4)alkyl, (C1-4)alkoxy, trifluoromethyl, halogen, cyano, nitro, —CHO, —COO(C1-4)alkyl, —CO(C1-4)alkyl;
n represents 0, 1, 2, 3, 4 or 5;
R4 represents OH and
R5 and R6 represent H or C1-C4 alkyl or
R4 and R5 form a bond and
R6 represent H or C1-C4 alkyl or
R4 and R6 form a bond and
R5 represent H or C1-C4 alkyl;
in free base or acid addition saitform.

### Claim 2

A compound of formula (I′)
wherein
R1 represents hydrogen or C1-C4 alkyl and
R2 represents an unsubstituted or substituted heterocycle or
R1 represents hydrogen or C1-C4 alkyl and
R2 represents aryl or substituted aryl or
R1 and R2 together with the nitrogen atom form an unsubstituted or substituted heterocycle;
R3 represents (C1-4)alkyl, (C1-4)alkoxy, trifluoromethyl, halogen, cyano, nitro, —CHO, —COO(C1-4)alkyl, —CO(C1-4)alkyl.

### Claim 3

A compound of formula (II)
wherein
R3 represents (C1-4)alkyl, (C1-4)alkoxy, trifluoromethyl, halogen, cyano, nitro, —CHO, —COO(C1-4)alkyl, —CO(C1-4)alkyl;
N represents 0, 1, 2, 3, 4 or 5;
R5 and R6 represent H or C1-C4 alkyl.

### Claim 4

A process for the preparation of a compound of formula (I)
wherein
R1 represents hydrogen or C1-C4 alkyl and
R2 represents an unsubstituted or substituted heterocycle or
R1 represents hydrogen or C1-C4 alkyl and
R2 represents aryl or substituted aryl or
R1 and R2 together with the nitrogen atom form an unsubstituted or substituted heterocycle;
R3 represents (C1-4 alkyl (C1-4) alkoxy trifluoromethyl, halogen, cyano, nitro, —CHO, —COO(C1-4)alkyl, —CO(C1-4)alkyl;
n represents 0, 1, 2, 3, 4 or 5;
R4 represents OH and
R5 and R6 represent H or C1-C4 alkyl or
R4 and R5 form a bond and
R6 represent H or C1-C4 alkyl or
R4 and R6 form a bond and
R5 represent H or C1-C4 alkyl;
in free base or acid addition salt form, comprising:
a)for the production of a compound of formula (I) wherein i) R4 represents hydroxy, R1 represents hydrogen or C1-C4 alkyl and R2 represents an unsubstituted or substituted heterocycle or ii) R1 represents hydrogen or C1-C4 alkyl and R2 represents aryl or substituted aryl, by reductive amination of a compound of formula (II)
wherein R6, R5, R3, n are as defined above, with a compound of formula (III)
wherein R1 and R2 are as defined above, or
b) for the production of a compound of formula (I) wherein R4 represents hydroxy, R1 and R2 together with the nitrogen atom form an unsubstituted or substituted heterocycle, by cyclocondensation of a compound of formula (IV)
c) for the production of a compound of formula (I) wherein R4 represents hydroxy, R1 and R2 together with the nitrogen atom form an unsubstituted or substituted heterocycle, by reductive alkylation of a compound of formula (V)
wherein R6, R5, R2, R1 are as defined above, with a compound of formula (VI) with a compound of formula (VI)
wherein R3 and n are as defined above, or
d) for the production of a compound of formula (I) wherein i) R4 and R5 form a bond and R6 represents hydrogen or C1-C4 alkyl or ii) wherein R4 and R6 form a bond and R5 represents hydrogen, by dehydrating a compound of formula (I) wherein R4 is hydroxyl R5 and R6 are hydrogen or C1-C4 alkyl;
and recovering the resulting compound of formula (I) in free base or acid addition salt form.

### Claim at position 5

5-6. (canceled)

### Claim 7 (depends on 1)

A pharmaceutical composition comprising
the compound of claim 1 in free base or pharmaceutically acceptable acid addition salt form, in association with a pharmaceutical carrier or diluent.

### Claim at position 7

8-9. (canceled)

### Claim 10 (depends on 1)

A method of treating disorders associated with irregularites of the glutamatergic signal transmission, and nervous system disorders mediated full or in part by mGluR5, comprising:
administering to a subject in need of such treatment a therapeutically effective amount of the compound of claim 1 in free base or pharmaceutically acceptable acid addition salt form.