Stereoisomers of benzonitrile derivatives, useful as cardiac arr

Details Stereoisomers of benzonitrile derivatives, useful as cardiac arr Stereoisomers of benzonitrile derivatives, useful as cardiac arr

1990-06-18

1991-10-08

Richter, Johann

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Ester doai

558413, A61K 3110, A61K 31045, C07C25550

Patent

active

050554905

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

The present invention relates to stereoisomers of the compound 4-[3-[ethyl[3-(propylsulfinyl)propyl]amino]-2-hydroxypropoxy]-benzonitrile , its preparation and use.


BACKGROUND OF THE INVENTION

Our prior patent application PCT/SE88/00691, filed on Dec. 20, 1988 and published after the filing date of this application, relates to a group of novel compounds which are useful in the treatment, acute as well as long term, of cardiac arrhythmias of diverse etiology. Among the compounds included in the group of compounds disclosed in said application is the compound 4-[3-[ethyl[3-(propylsulfinyl)propyl]amino]-2-hydroxypropoxy]-benzonitrile having the formula I ##STR1## which can be obtained as a stereoisomeric mixture as well as in the form of the different isomers; the following two stereoisomers are mentioned in the said application: le, le.


THE INVENTION

The compound of the formula I having two chiral centra (*) ##STR2##
It has now been found that the stereoisomers of the compound of formula I above i.e. nitrile, nitrile, nitrile nitrile, and pharmaceutically acceptable salts thereof, of cardiac arrhythmias of diverse etiology.
An object is to provide antiarrhythmics which have less prominent side effects than existing antiarrhythmic drugs. The compounds should for instance be free of negative inotropic effect and the compounds may even be positively inotropic. The compounds should further separate the anti-arrhythmic effect from central nervous and gastrointestinal effects.
The stereoisomers of this invention may be used therapeutically in the stereochemical pure forms.
The present invention also relates to processes for the preparation of said isomers according to the present invention.
A. The compounds of the formula ##STR3## can be prepared by reaction of a compound of the formula ##STR4## with a compound of the formula ##STR5##
The reaction is typically carried out in a suitable solvent such as isopropanol or N,N-dimethylformamide. The mixture should be heated to a temperature in the range 40.degree.-100.degree. C. until the reaction is completed. Thereafter the product can be isolated by conventional methods; or
B. A compound of the formula ##STR6## can be prepared by reacting a compound of the formula ##STR7## where M is methyl or a 4-methyl-phenyl residue, with a compound of the formula ##STR8##
The reaction is typically carried out in a suitable organic solvent such as acetonitrile or N,N-dimethylformamide. A suitable organic or inorganic base such as triethylamine or potassium carbonate is added to the mixture. The mixture is then heated to a temperature in the range of 90.degree.-100.degree. C. until the reaction is completed after which the products can be isolated and purified by conventional methods.
The invention further relates to a method of preventing or reducing cardiac arrhythmias in mammals, including man, which comprises administering to a host in need of such treatment an effective amount of said stereoisomer of the compound of the formula I or pharmaceutically acceptable salts thereof.
The invention yet further relates to said stereoisomers of the compound of the formula I or pharmaceutically acceptable salts thereof for use as a medicament, particularly as an antiarrhythmic agent.
The invention also relates to the use of the stereoisomers of the compound of the formula I for the manufacture of medicaments with action against cardiac arrhythmias.
The following non-limiting examples further illustrate the invention.


EXAMPLE 1



4-[3-[ethyl[3-((S*)-propylsulfinyl)propyl]amino]-2(R)-hydroxypropoxy]-benzo
nitrile


a) Ethyl(3-(S*)-propylsulfinyl)propylamine

A hot solution of 27.2 g (0.1 mol) of (-)-1,3,2-dioxaphosphorinane-5,5-dimethyl-2-hydroxy-4-(2-methoxyphenyl)-2- oxide and 17.73 g (0.1 mol) of racemic ethyl (3-propylsulfinyl)-propylamine in 750 ml of acetone and 32.5 ml of methanol was allowed to cool to room temperature, yielding 23.9 g of crystalline material. The experiment was repeated on a 0.25 mol scale, this time yielding 53.0 g of crystals. The

REFERENCES:
Almgren et al., Chem. Abstracts, vol. 112, No. 1; 7180y (1990).

Affiliated with

Also associated with

Rating

Stereoisomers of benzonitrile derivatives, useful as cardiac arr does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Stereoisomers of benzonitrile derivatives, useful as cardiac arr, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Stereoisomers of benzonitrile derivatives, useful as cardiac arr will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-257369