Anticholinergics which may be used as medicaments as well as processes for preparing them

• US 7,569,581 B2
• Filed: 04/28/2005
• Issued: 08/04/2009
• Est. Priority Date: 10/14/2000
• Status: Expired due to Term

• Current Assignee: Boehringer Ingelheim Pharma GmbH & Company Kg (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim Pharma GmbH & Company Kg (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Pieper, Michael Paul, Meissner, Helmut, Banholzer, Rolf, Speck, Georg, Pohl, Gerald, Morschhaeuser, Gerd, Reichl, Richard
• Primary Examiner(s): Seaman; D. Margaret
• Assistant Examiner(s): Rahmani; Niloofar
• Application Number:
  US11/117,163
• Publication Number:
  US 20050197357A1
• Time in Patent Office: 1,559 Days
• Field of Search: 514/304
• US Class Current: 514/304
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 451/10 acylated by aliphatic or araliphatic carboxylic acids, e.g. atropine, scopolamine

Abstract

The present invention relates to new anticholinergics of general formula 1

wherein A, X⁻, and the groups R¹, R², R³, R⁴, R⁵, R⁶ and R⁷ may have the meanings given in the claims and in the specification, processes for preparing them and their use as pharmaceutical compositions.

Claims

1. A method of treating asthma or COPD in a host in need thereof comprising administering by inhalation to the host an effective amount of a compound of formula 1

2. The method according to claim 1, wherein in the compound of formula 1:

X⁻

is an anion with a single negative charge selected from chloride, bromide, methylsulphate, 4-toluenesulphonate, and methanesulphonate;

R¹ and R², which are identical or different, are each a group selected from methyl, ethyl, n-propyl, and isopropyl, which are optionally substituted by hydroxy or fluorine;

R³, R⁴, R⁵, and R⁶, which are identical or different, are each hydrogen, methyl, ethyl, methyloxy, ethyloxy, hydroxy, fluorine, chlorine, bromine, CN, CF₃, or NO₂; and

R⁷ is methyl, ethyl, methyloxy, ethyloxy, —

CH₂—

F, —

CH₂—

CH₂—

F, —

O—

CH₂—

F, —

O—

CH₂—

CH₂—

F, —

CH₂—

OH, —

CH₂—

CH₂—

OH, CF₃, —

CH₂—

OMe, —

CH₂—

CH₂—

OMe, —

CH₂—

OEt, —

CH₂—

CH₂—

OEt, —

O—

COMe, —

O—

COEt, —

O—

COCF₃, —

O—

COCF₃, fluorine, chlorine, or bromine.

3. The method according to claim 2, wherein in the compound of formula 1:

X⁻

is an anion with a single negative charge selected from chloride, bromide, and methanesulphonate;

R¹ and R², which are identical or different, are each methyl or ethyl, which are optionally substituted by hydroxy or fluorine;

R³, R⁴, R⁵, and R⁶, which are identical or different, are each hydrogen, methyl, ethyl, methyloxy, ethyloxy, hydroxy, fluorine, chlorine, or bromine; and

R⁷ is methyl, ethyl, methyloxy, ethyloxy, CF₃, or fluorine.

4. The method according to claim 3, wherein in the compound of formula 1:

X⁻

is bromide;

R¹ and R², which are identical or different, are each methyl or ethyl;

R³, R⁴, R⁵, and R⁶, which are identical or different, are each hydrogen, methyl, methyloxy, chlorine, or fluorine; and

R⁷ is methyl or fluorine.

5. The method according to claim 4, wherein in the compound of formula 1:

X⁻

is bromide;

R¹ and R², which are identical or different, are each methyl or ethyl;

R³, R⁴, R⁵, and R⁶, which are identical or different, denote hydrogen or fluorine; and

R⁷ is methyl or fluorine.

6. The method according to one of claim 1 to 5, wherein the method further comprises administering by inhalation to the host at least one additional active substance selected from the group consisting of:

betamimetics, antiallergic agents, PAF-antagonists, leukotriene-antagonists, and steroids.

7. The method according to claim 1 or 5, wherein the compound of formula 1 is scopine 2,2-diphenylpropionate methobromide.

8. The method according to claim 1 or 5, wherein the compound of formula 1 is scopine 2-fluoro-2,2-diphenylacetate methobromide.

9. The method according to claim 1 or 5, wherein the compound of formula 1 is tropenol 2,2-diphenylpropionate methobromide.

10. The method according to claim 1 or 5, wherein the compound of formula 1 is tropenol 2-fluoro-2,2-bis(3 ,4-difluorophenyl)acetate methobromide.

11. The method according to claim 1 or 5, wherein the compound of formula 1 is scopine 2,2-diphenylpropionate ethylbromide.

12. The method according to claim 1 or 5, wherein the compound of formula 1 is scopine 2-fluoro-2,2-bis(3,4-difluorophenyl)acetate methobromide.

13. The method according to claim 1 or 5, wherein the compound of formula 1 is tropenol 2-fluoro-2,2-bis(4-fluorophenyl)acetate methobromide.

14. The method according to claim 1 or 5, wherein the compound of formula 1 is scopine 2-fluoro-2,2-bis(4-fluorophenyl)acetate methobromide.

15. The method according to claim 1 or 5, wherein the compound of formula 1 is tropenol 2-fluoro-2,2-diphenylacetate methobromide.

16. The method according to claim 1 or 5, wherein the compound of formula 1 is tropenol 2-fluoro-2,2-(3-chlorophenyl)acetate methobromide.