Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Patent
1998-04-27
2000-10-03
Spivack, Phyllis G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
514656, 514657, A61K 31137
Patent
active
061274240
DESCRIPTION:
BRIEF SUMMARY
The invention relates to use of aryl-substituited cyclobutylalkylamines for treating obesity. DE 32 12 682 C2 discloses aryl-substituted cyclobutylalkylamines. The compounds disclosed therein are employed as antidepressants.
WO 90/06110 discloses the use of N,N-dimethyl-1-1[1-(4-chlorophenyl)cyclobutyl]-3-methylbutylamine hydrochloride for treating obesity.
It has now been found, surprisingly, that a certain group of the compounds disclosed in DE 32 12 682 C2 is more suitable for treating obesity than the hydrochloride described in WO 90/06110 for this purpose. The present invention therefore relates to the use of aryl-substituted cyclobutylalkylamines of the formula I ##STR1## where n is 0 or 1, having 1 to 6 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, a cycloalkylalkyl group in which the cycloalkyl group contains 3 to 6 carbon atoms and the alkyl group contains 1 to 3 carbon atoms, an alkenyl or an alkynyl group having 2 to 6 carbon atoms, it being possible for the alkyl group, the cycloalkyl group, the cycloalkylalkyl group, the alkenyl or alkynyl group to contain at least one substituent which is selected from the group consisting of hydroxyl and acylated derivatives thereof, alkoxy groups, unsubstituted or substituted by hydroxyl, oxo, alkoxy, carbamoyl, carbocyclic or heterocyclic groups, cycloalkyloxy groups having 3 to 6 carbon atoms, alkylenedioxy groups, oxo- and groups of the formula S(O).sub.p R.sup.5, where p is 0, 1 or 2, and R.sup.5 is an alkyl group having 1 to 3 carbon atoms, it being possible for the aliphatic group to be substituted by other substituents selected from carbocyclic groups having 3 to 6 carbon atoms, heterocyclic groups or halogen atoms, ##STR2## where R.sup.9 and R.sup.10, which can be identical or different, are a hydrogen atom, a halogen atom or an alkoxy group having 1 to 3 carbon atoms, atoms, having 1 to 4 carbon atoms, an alkenyl group having 3 to 6 carbon atoms, an alkynyl group having 3 to 6 carbon atoms, or a cycloalkyl group in which the ring contains 3 to 7 carbon atoms, atom, a halogen atom, a trifluoromethyl group, an alkyl group having 1 to 3 carbon atoms, an alkoxy or alkylthio group having 1 to 3 carbon atoms or a phenyl group, or together with the carbon atoms to which they are bonded form a second benzene ring which is unsubstituted or substituted by one or more halogen atoms, one alkyl or alkoxy group having 1 to 4 carbon atoms, or the substituents in the second benzene ring form, together with the two carbon atoms to which they are bonded, another benzene ring, and atom or an alkyl group having 1 to 3 carbon atoms, accompanying disorders.
The compounds used according to the invention have the advantage of very good bioavailability and show a more favorable spectrum of side effects.
In the formulae present in this description and the claims, the symbol ##STR3## means a 1,1-disubstituted cyclobutane group of the formula ##STR4## and --CR.sup.1 R.sup.2 (CR.sup.7 R.sup.8).sub.n NR.sup.3 R.sup.4 means a group of the following formula ##STR5##
Preferred compounds of the formula I, in which n is 0 are those where R.sup.1 is a straight-chain or branched-chain alkyl group having 1 to 4 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, a cycloalkylmethyl group, in which the cycloalkyl ring contains 3 to 6 carbon atoms, or a group of the formula II in which R.sup.9 and/or R.sup.10 are a hydrogen atom, a fluorine atom or methoxy, and R.sup.2 is a hydrogen atom or methyl. Examples of particularly preferred compounds of the formula I are those where R.sup.1 is methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl and phenyl, if n is 0, and R.sup.2 is a hydrogen atom.
Compounds of the formula I wherein n is 0 can alternatively be represented by formula Ia: ##STR6##
Preferred compounds of he formula I in which n is 1 are those where R.sup.1 is a hydrogen atom or methyl, and R.sup.2 is a hydrogen atom. Particularl
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Heal David John
Martin Keith Frank
Knoll Aktiengesesllschaft
Spivack Phyllis G.
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