Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Reexamination Certificate
2000-03-17
2002-03-12
Krass, Frederick (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
C514S649000, C514S650000, C514S654000
Reexamination Certificate
active
06355685
ABSTRACT:
This invention relates to a method of treating anxiety disorders.
Anxiety disorders include, but are not limited to the following, panic attacks, phobic disorders, post-traumatic stress disorder, mixed anxiety and depressive disorders and agrophobia and other similar conditions known to those skilled in the art. Further details of each of these conditions may be found in Martindale, The Extra Pharmacopoeia, 31
st
edition, p.670.
According to the present invention there is provided a method of treating anxiety disorders, in which a therapeutically effective amount of a compound of formula I
including enantiomers and pharmaceutically acceptable salts thereof, in which R
1
and R
2
are independently H or methyl, is administered in conjunction with a pharmaceutically acceptable diluent or carrier to a human in need thereof.
The compounds of formula I are advantageous in that they may be used to provide a higher degree of efficacy and a lower degree of side effects compared to the conventional treatments.
A preferred compound of formula I is N,N-dimethyl-1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutylamine or a salt thereof, for example the hydrochloride salt. A preferred form of this hydrochloride is its monohydrate.
The preparation and use of compounds of formula 1, such as N,N-dimethyl-1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutylamine and salts thereof, in the treatment of depression is described in British Patent Specification 2098602. The use of compounds of formula I such as N,N-dimethyl-1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutylamine and salts thereof in the treatment of Parkinson's disease is described in published PCT application WO 88/06444. The use of N,N-dimethyl-1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutylamine and salts thereof in the treatment of cerebral function disorders is described in U.S. Pat. No. 4,939,175. The use of N,N-dimethyl-1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutylamine hydrochloride in the treatment of obesity is described in published PCT application WO090/06110. A particularly preferred form of this compound is N,N-dimethyl-1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutylamine hydrochloride monohydrate (sibutramine hydrochloride) which is described in European Patent Number 230742. The use of N,N-dimethyl-1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutylamine and salts thereof for improving the glucose tolerance of humans having Impaired Glucose Tolerance or Non-Insulin Dependent Diabetes Mellitus is described in published PCT application WO095120949.
It will be appreciated by those skilled in the art that compounds of formula I contain a chiral centre. When a compound of formula I contains a single chiral centre it may exist in two enantiomeric forms. The present invention includes the use of the individual enantiomers and mixtures of the enantiomers. The enantiomers may be resolved by methods known to those skilled in the art, for example by formation of diastereoisomeric salts or complexes which may be separated, for example, by crystallisation; via formation of diastereoisomeric derivatives which may be separated, for example, by crystallisation, gas-liquid or liquid chromatography; selective reaction of one enantiomer with an enantiomer-specific reagent, for example enzymatic oxidation or reduction, followed by separation of the modified and unmodified enantiomers; or gas-liquid or liquid chromatography in a chiral environment, for example on a chiral support, for example silica with a bound chiral ligand or in the presence of a chiral solvent. It will be appreciated that where the desired enantiomer is converted into another chemical entity by one of the separation procedures described above, a further step is required to liberate the desired enantiomeric form. Alternatively, specific enantiomers may be synthesised by asymmetric synthesis using optically active reagents, substrates, catalysts or solvents, or by converting one enantiomer to the other by asymmetric transformation.
Preferred compounds of formula I are N,N-dimethyl-1-[1-(4-chlorophenyl)-cyclobutyl]-3-methylbutylamine, N-{1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}-N-methylamine, and 1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutylamine including racemates, individual enantiomers and mixtures thereof, and pharmaceutically acceptable salts thereof.
The individual enantiomers can be prepared by enantioselective synthesis from optically active precursors, or by resolving the racemic compound which can be prepared as described above. Enantiomers of secondary amines of the formula I can also be prepared by preparing the racemate of the corresponding primary amine, resolving the latter into the individual enantiomers, and then converting the optically pure primary amine enantiomer into the required secondary amine by methods described in British Patent Specification 2098602.
REFERENCES:
patent: 4522828 (1985-06-01), Jeffery et al.
patent: 5135947 (1992-08-01), Robertson et al.
Chemical Abstract 128:70669, “In vivo criteria to differentiate monamine reuptake inhibitors from releasing agents: sibutramine is a reuptake inhibitor”.*
Gundlah, et al, In vivo Criteria to differentiate monoamine reuptake inhibitors from releasing agents: sibutramine is a reuptake inhibitor Database CA on STN, Feb. 1997, pp. 581-591, vol. 283 No. 2, Chemical abstracts service (Columbus, Ohio).
Koshino. “Treatment of Panic Disorders with SSRI,” Database CA on STN. Apr. 1995, pp. 257-264, vol. 17, No. 4, Chemical Abstracts Service (Columbus, Ohio).
Cheetham Sharon C.
Heal David J.
Luscombe Graham P.
Conway John D.
Knoll Pharmaceutical Company
Krass Frederick
LandOfFree
Method of treating anxiety disorders does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method of treating anxiety disorders, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of treating anxiety disorders will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2875738