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

• US 20020115680A1
• Filed: 10/11/2001
• Published: 08/22/2002
• Est. Priority Date: 10/14/2000
• Status: Active Grant

• 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: Banholzer, Rolf, Pieper, Michael Paul, Meissner, Helmut, Speck, Georg, Pohl, Gerald, Morschhaeuser, Gerd, Reichl, Richard
• Granted Patent: US 6,706,726 B2
• Time in Patent Office: Days
• US Class Current: 514/291
• 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 pharamaceutical compositions.

Claims

1. ) A compound of formula 1

2. ) A compound of formula 1 according to claim 1, wherein

A denotes a double-bonded group selected from among

X ⁻

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

R¹ and R² which may be identical or different denote a group selected from among methyl, ethyl, n-propyl and iso-propyl, which may optionally be substituted by hydroxy or fluorine;

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

R⁷ denotes hydrogen, methyl, ethyl, methyloxy, ethyloxy, —

CH₂—

F, —

CH₂—

CH₂—

F, —

O—

CH₂13 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,

optionally in the form of the individual optical isomers, mixtures of the individual enantiomers or racemates thereof.

3. ) A compound of formula 1 according to claim 2, wherein

A denotes a double-bonded group selected from among

X ⁻

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

R¹ and R² which may be identical or different denote a group selected from methyl and ethyl, which may optionally be substituted by hydroxy or fluorine;

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

R⁷ denotes hydrogen, methyl, ethyl, methyloxy, ethyloxy, CF₃ or fluorine,

optionally in the form of the individual optical isomers, mixtures of the individual enantiomers or racemates thereof.

4. ) A compound of formula 1, according to claim 3, wherein

A denotes a double-bonded group selected from among

X ⁻

denotes bromide;

R¹ and R² which may be identical or different denote a group selected from methyl and ethyl;

R³, R⁴, R⁵ and R⁶, which may be identical or different, denote hydrogen, methyl, methyloxy, chlorine or fluorine;

R⁷ denotes hydrogen, methyl or fluorine,

optionally in the form of the individual optical isomers, mixtures of the individual enantiomers or racemates thereof.

5. ) A compound of formula 1, according to claim 4, wherein

A denotes a double-bonded group selected from among

X ⁻

denotes bromide;

R¹ and R² which may be identical or different denote methyl or ethyl;

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

R⁷ denotes hydrogen, methyl or fluorine,

optionally in the form of the individual optical isomers, mixtures of the individual enantiomers or racemates thereof.

6. ) A method of treating a disease that is responsive to anticholinergic activity, comprising administering to a host in need thereof an effective amount of a compound of formula 1 according to claim 1.

7. ) A method according to claim 6, wherein the disease is selected from asthma, COPD, vagally induced sinus bradycardia, heart rhythm disorders, spasms in the gastrointestinal tract, spasms in the urinary tract and menstrual disorders.

8. ) A pharmaceutical composition comprising one or more compounds of formula 1 according claim 1, or a physiologically acceptable salt thereof, optionally together with one or more conventional excipients and/or carriers.

9. ) A pharmaceutical composition according to claim 8, further comprising at least one additional active substance selected from among the betamimetics, antiallergic agents, PAF-antagonists, leukotriene-antagonists and steroids.

10. ) A process for preparing a compound of formula 1 according to claim 1

11. ) A compound of formula 4