Amides of acetic and propionic acids

Patent metadata

Field	Value
Publication number	US-9433614-B2
Application number	US-201514633985-A
Country	US
Kind code	B2
Filing date	Feb 27, 2015
Priority date	Mar 15, 2002
Publication date	Sep 6, 2016
Grant date	Sep 6, 2016

Abstract

The invention relates to novel amides of acetic and propionic acids, methods for production and use thereof for the production of medicaments for the treatment and/or prophylaxis of diseases and for improving perception, concentration, learning ability and memory.

First claim

The invention claimed is:

1. A method of treating a cognitive impairment in a patient in need thereof, comprising administering to the patient a compound represented by formula (I)

in which
R 1 is 1-azabicyclo[2.2.2]oct-3-yl optionally substituted by (C 1 -C 6 )-alkyl,
A is methylene or ethylene,
R 2 is benzothiophenyl optionally substituted by radicals selected from the group of halogen, formyl, —CO—NR 4 R 5 , —CO—OR 6 , —NR 7 R 8 , —NR 9 —CO—R 10 , cyano, trifluoromethyl, trifluoromethoxy, nitro, optionally hydroxyl-, amino-, —NH—CO—R 11 — or cyano-substituted (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxy, (C 1 -C 6 )-alkylthio,
in which R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 are independently of one another hydrogen, (C 1 -C 6 )-alkyl, phenyl or benzyl,
and

R 3 is hydrogen or (C 1 -C 6 )-alkyl,
or a salt thereof.

2. The method of claim 1 , wherein the cognitive impairment is Alzheimer's disease.

3. The method of claim 2 , wherein
R 1 is 1-azabicyclo[2.2.2]oct-3-yl,
and R 2 and R 3 have the meaning indicated in claim 1 ,
or a salt thereof.

4. The method of claim 3 , wherein
A represents a methylene;
R 2 represents benzotriazolyl optionally substituted by 1 to 3 radicals selected from the group of hydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, (C 1 -C 4 )-alkylthio, and
R 3 represents hydrogen.

5. The method of claim 3 , where
R 1 is 1-azabicyclo[2.2.2]oct-3-yl,
A is methylene,
R 2 is benzothiophenyl where the rings are optionally substituted by 1 to 3 radicals selected from the group of hydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, (C 1 -C 4 )-alkylthio,
and
R 3 is hydrogen,
or a salt thereof.

6. The method of claim 3 , where
R 1 is 1-azabicyclo[2.2.2)oct-3-yl,
A is methylene,
R 2 is benzothiophenyl, where the rings are optionally substituted by 1 to 2 radicals selected from the group of hydrogen, fluorine, chlorine, bromine, nitro
and
R 3 is hydrogen,
or a salt thereof.

7. A method of treating a cognitive impairment in a patient in need thereof, comprising administering to the patient a pharmaceutical composition comprising: i) a compound represented by formula (I)

in which
R 1 is 1-azabicyclo[2.2.2]oct-3-yl optionally substituted by (C 1 -C 6 )-alkyl,
A is methylene or ethylene,
R 2 is benzothiophenyl optionally substituted by radicals selected from the group of halogen, formyl, —CO—NR 4 R 5 , —CO—OR 6 , —NR 7 R 8 , —NR 9 —CO—R 10 , cyano, trifluoromethyl, trifluoromethoxy, nitro, optionally hydroxyl-, amino-, —NH—CO—R 11 — or cyano-substituted (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkoxy, (C 1 -C 6 )-alkylthio,
in which R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 are independently of one another hydrogen, (C 1 -C 6 )-alkyl, phenyl or benzyl,
and

R 3 is hydrogen or (C 1 -C 6 )-alkyl,
or a salt thereof; and
ii) one or more pharmaceutically acceptable carriers or excipients.

8. The method of claim 7 , wherein the cognitive impairment is Alzheimer's disease.

9. The method of claim 8 , wherein
R 1 is 1-azabicyclo[2.2.2]oct-3-yl,
and R 2 and R 3 have the meaning indicated in claim 7 ,
or a salt thereof.

10. The method of claim 9 , wherein
A represents a methylene;
R 2 represents benzotriazolyl optionally substituted by 1 to 3 radicals selected from the group of hydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, (C 1 -C 4 )-alkylthio, and
R 3 represents hydrogen.

11. The method of claim 9 , where
R 1 is 1-azabicyclo[2.2.2]oct-3-yl,
A is methylene,
R 2 is benzothiophenyl, where the rings are optionally substituted by 1 to 3 radicals selected from the group of hydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxy, nitro, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy, (C 1 -C 4 )-alkylthio,
and
R 3 is hydrogen,
or a salt thereof.

12. The method of claim 9 , where
R 1 is 1-azabicyclo[2.2.2)oct-3-yl,
A is methylene,
R 2 is benzothiophenyl, where the rings are optionally substituted by 1 to 2 radicals selected from the group of hydrogen, fluorine, chlorine, bromine, nitro
and
R 3 is hydrogen,

or a salt thereof.

Assignees

• Bayer Ip Gmbh

Inventors

• Luithle Joachim
• Bob Frank-Gerhard
• Erb Christina
• Schnizler Katrin
• Flessner Timo
• Kampen Marja V
• Methfessel Christoph

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/14

  for treating abnormal movements, e.g. chorea, dyskinesia · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title