N-(2-Aminocycloheptyl)alkanoylanilides
AssigneeThe Upjohn Company
InventorJacob Szmuszkovicz
Life of this patent
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Abstract
N-(2-aminocycloheptyl)N-alkanoylanilides and their 2-N-oxides of the formula ##STR1## e.g., trans-3,4-dichloro-N-[2-(allylamino)cycloheptyl]propionanilide, and their pharmacologically acceptable salts, have been found to possess potent Central Nervous System antidepressant properties. Many of them are new. These compounds are promising antidepressant drugs which are characterized by lower toxicity than imipramine, and long acting activity which may allow longer durations between administrations, e.g., once a day. Pharmaceutical compositions containing these compounds and a process for treating conditions of depression with these compositions are disclosed.
Claims24
A process for treating depression which comprises administering to a depressed human a compound of the formula ##STR22## wherein the wavy line (.about.) in the 1-position of the cycloheptyl ring indicates cis or trans configuration of the substituents in the 1- and 2-positions of the [cyclopentyl] cycloheptyl ring;
- p is zero or 1;
- Q is oxygen or sulfur;
- R is C.sub.1 to C.sub.3 -alkyl, vinyl, C.sub.3 to C.sub.6 -cycloalkyl, ethoxy, or methoxymethyl;
- R.sub.1 is hydrogen or C.sub.1 to C.sub.3 -alkyl;
- R.sub.2 is:
- --CH.sub.2 C.sub.6 H.sub.5,
- --CH.sub.2 CH.sub.2 --C.sub.6 H.sub.5, or
- C.sub.3 -C.sub.6 (allylic)alkenyl;
- each of Y and Z is selected from the group consisting of hydrogen, a halogen having an atomic number of from 9 to 35, trifluoromethyl, C.sub.1 to to C.sub.2 -alkyl, and C.sub.1 to C.sub.2 -alkyloxy and when Y is trifluoromethyl, Z is hydrogen;
- when Y is C.sub.1 to C.sub.2 -alkyloxy and Z is hydrogen, the C.sub.1 to C.sub.2 -alkyloxy is in the 3-position;
- when Y and Z are both halogens or C.sub.1 to C.sub.2 -alkyloxy, they are present in the 3-and 4- or 3- and 5-positions, or a pharmacologically acceptable salt thereof, in an amount ranging from about 4 to about 400 mg. per dosage unit to alleviate the conditions of depression, in association with a pharmaceutical carrier.
A pharmaceutical preparation in dosage unit form adapted for administration to obtain an anti-depression effect comprising per dosage unit an anti-depressant effective, non-toxic amount of a compound of the formula ##STR23## wherein the wavy line (.about.) in the 1-position of the [cyclopentyl] cycloheptyl ring indicates cis or trans configuration of the substituents in the 1- and 2-positions of the [cyclopentyl] cycloheptyl ring;
- [P] p is zero or 1;
- Q is oxygen or sulfur;
- R is C.sub.1 to C.sub.3 -alkyl, vinyl, C.sub.3 to C.sub.6 -cycloalkyl, ethoxy, or methoxymethyl;
- R.sub.1 is hydrogen or C.sub.1 to C.sub.3 -alkyl;
- R.sub.2 is:
- --CH.sub.2 C.sub.6 H.sub.5,
- --CH.sub.2 CH.sub.2 C.sub.6 H.sub.5, or
- C.sub.3 to C.sub.6 -(allylic)alkenyl;
- each of Y and Z is selected from the group consisting of hydrogen, a halogen having an atomic number of from 9 to 35, trifluoromethyl, C.sub.1 to to C.sub.2 -alkyl, and C.sub.1 to C.sub.2 -alkyloxy and when Y is trifluoromethyl, Z is hydrogen;
- when Y is C.sub.1 to C.sub.2 -alkyloxy and Z is hydrogen, the C.sub.1 to C.sub.2 -alkyloxy is in the 3-position;
- when Y and Z are both halogens or C.sub.1 to C.sub.2 -alkyloxy, they are present in the 3- and 4- or 3- and 5-positions, or a pharmacologically acceptable salt thereof, in an amount ranging from about 4 to about 400 mg. per dosage unit to alleviate the conditions of depression, in association with a pharmaceutical carrier.
A pharmaceutical preparation according to claim .Badd.[13].Baddend. 12 wherein the compound of formula I therein is 3,4-dichloro-N-[2-(N-allylamino)cycloheptyl]propionanilide, or a pharmacologically acceptable salt thereof.
A compound of the formula ##STR24## wherein the wavy line (.about.) in the 1-position of the [cyclopentyl] cycloheptyl ring indicates cis or transconfiguration of the substituents in the 1- and 2-positions of the [cyclopentyl] cycloheptyl ring;
- p is zero or 1;
- Q is oxygen or sulfur;
- R is C.sub.1 to C.sub.3 -alkyl, vinyl C.sub.3 to C.sub.6 -cycloalkyl, ethoxy, or methoxymethyl;
- R.sub.1 is hydrogen or C.sub.1 to C.sub.3 -alkyl;
- R.sub.2 is C.sub.3 to C.sub.6 -(allylic)alkenyl;
- each of Y and Z is selected from the group consisting of hydrogen, a halogen having an atomic number of from 9 to 35, trifluoromethyl, C.sub.1 to C.sub.2 -alkyl, and C.sub.1 to C.sub.2 -alkyloxy and when Y is trifluoromethyl, Z is hydrogen;
- when Y is C.sub.1 to C.sub.2 -alkyloxy and Z is hydrogen, the C.sub.1 to C.sub.2 -alkyloxy is in the 3-position;
- when Y and Z are both halogens or C.sub.1 to C.sub.2 -alkyloxy, they are present in the 3- and 4- or 3- and 5-positions, or an acid addition salt thereof.
3,4-Dichloro-N-[2-(N-allyl-N-methylamino)cyloheptyl]propionanilide and the acid addition salts thereof.
3,4-Dichloro-N-[2-(N-.beta.-p henethyl-N-methylamino)cycloheptyl]propionanilide and the acid addition salts thereof.
3,4-Dichloro-N-[2-(N-benzyl-N-methylamino)cycloheptyl]propionanilide, and the acid addition salts thereof.
A compound of the formula ##STR25## wherein the wavy line (.about.) in the 1-position of the cycloheptyl ring indicates cis or trans configuration of the substituents in the 1- and 2-positions of the [cyclopentyl] cycloheptyl ring;
- [P] p is zero or 1;
- Q is oxygen or sulfur;
- R is vinyl, C.sub.3 to C.sub.6 -cycloalkyl, ethoxy, or methoxymethyl;
- R.sub.1 is hydrogen or C.sub.1 to C.sub.3 -alkyl;
- R.sub.2 is C.sub.3 to C.sub.6 -(allylic)alkenyl), benzyl or phenylethyl,
- each of Y and Z is selected from the group consisting of hydrogen, a halogen having an atomic number of from 9 to 35, trifluoromethyl, C.sub.1 to C.sub.2 -alkyl, and C.sub.1 to C.sub.2 -alkyloxy and when Y is trifluoromethyl, Z is hydrogen[,] ;
- when Y is C.sub.1 to C.sub.2 -alkyloxy and Z is hydrogen, the C.sub.1 to C.sub.2 -alkyloxy is in the 3-position[,] ;
- when Y and Z are both halogens or C.sub.1 to C.sub.2 -alkyloxy, they are present in the 3- and 4- or 3- and 5-positions, or a pharmacologically acceptable salt thereof.
Dependencies are inferred from the claim text.