Substituted amidines having high binding to the sigma receptor and the use thereof
AssigneeState of Oregon, acting by and through the Oregon State Board of Higher Education
InventorsJohn F. W. Keana, Eckard Weber
Life of this patent
Estimating the term…
Abstract
N,N'-disubstituted-amidines, e.g., of the formula ##STR1## wherein R, R' and R" are substituted or unsubstituted hydrocarbon and/or heterocyclic groups. Methods are provided for the treatment or prophylaxis of anxiety in an animal, for treating psychosis, and for treating hypertension by administering an effective amount of an N,N'-disubstituted amidine which, preferably, has a high affinity for the sigma receptor.
Claims51
A method for the treatment or prophylaxis of anxiety in an animal susceptible to anxiety comprising the administration to an animal exhibiting symptoms of anxiety or susceptible to anxiety, of an anxiolytic amount of an N,N'-disubstituted amidine having the formula:
- ##STR8## where R and R" are a cycloalkyl group of at least 5 carbon atoms, a carbocyclic aryl group of at least 6 carbon atoms, alkaryl or aralkyl of at least 6 carbon atoms and containing 1-3 separate or fused rings, or a heterocyclic ring, wherein each of R and R" may be substituted in1-3 positions, or wherein R and R" together with the amidine group form a saturated or unsaturated cyclic ring containing at least 2 carbon atoms exclusive of the amidine carbon atom, wherein said cyclic ring may be substituted with one or more alkyl groups of 1-6 carbon atoms, carbocyclic aryl groups of at least 6 carbon atoms, cycloalkyl groups of 3-12 carbon atoms, or 1-2 fused aromatic rings;
- and
- R' is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, trifluoromethyl, or C.sub.1 -C.sub.6 alkylsulfonyl.
A method for the treatment or prophylaxis of anxiety in an animal susceptible to anxiety comprising the administration to an animal exhibiting symptoms of anxiety or susceptible to anxiety comprising the administration to an animal exhibiting symptoms of anxiety or susceptible to anxiety, of an anxiolytic amount of an N,N'-disubstituted amidine having the formula:
- ##STR9## wherein X and Y are independently a branched or straight chain C.sub.1 -C.sub.8 unsaturated alkylene;
- R and R" are independently a cycloalkyl group of at least 5 carbon atoms, a carbocyclic aryl group of at least 6 carbon atoms, aralkyl of at least 6 carbon atoms and containing 1-3 separate or fused rings, or a heterocyclic ring, wherein each of R and R" may be substituted in 1-3 positions, or where R and R" form a bond to give a saturated or unsaturated cyclic ring containing at least 2 carbon atoms exclusive of the amidine carbon atom, wherein said cyclic ring may be substituted with one or more alkyl groups of 1-6 carbon atoms, carbocyclic aryl groups of at least 6 carbon atoms, cycloalkyl groups of 3-12 carbon atoms, or 1-2 fused aromatic rings;
- and
- R' is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, trifluoromethyl, or C.sub.1 -C.sub.6 alkylsulfonyl.
A method of treating abnormal psychotic behavior in a human being which comprises administering thereto, in an amount effective to ameliorate the abnormal psychotic behavior an N,N'-disubstituted amidine having the formula:
- ##STR10## wherein R and R" are a cycloalkyl group of at least 5 carbon atoms, a carbocyclic aryl group of at least 6 carbon atoms, alkaryl or aralkyl of at least 6 carbon atoms and containing 1-3 separate or fused rings, or a heterocyclic ring, wherein R and R" may be substituted in -3 positions, or wherein each of R and R" together with the amidine group form a saturated or unsaturated cyclic ring containing at least 2 carbon atoms exclusive of the amidine carbon atom, and wherein said cyclic ring may be substituted with one or more alkyl groups of 1-6 carbon atoms, carbocyclic aryl groups of at least 6 carbon atoms, cycloalkyl groups of 3-12 carbon atoms, or 1-2 fused aromatic rings;
- and
- R' is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, trifluoromethyl, or C.sub.1 -C.sub.6 alkylsulfonyl.
A method of treating abnormal psychotic behavior in a human being which comprises administering thereto, in an amount effective to ameliorate the abnormal psychotic behavior an N,N'-disubstituted amidine having the formula:
- ##STR11## wherein X and Y are independently a branched or straight chain C.sub.1 -C.sub.8 alkylene or a branched or straight chain C.sub.2 -C.sub.8 unsaturated alkylene;
- R and R" are independently a cycloalkyl group of at least 5 carbon atoms, a carbocyclic aryl group of at least 6 carbon atoms, aralkyl of at least 6 carbon atoms and containing 1-3 separate or fused rings, or a heterocyclic ring, wherein each of R and R" may be substituted in 1-3 positions, or wherein R and R" may form a bond to give a saturated or unsaturated cyclic ring containing at least 2 carbon atoms exclusive of the amidine carbon atoms, wherein said cyclic ring may be substituted with one or more alkyl groups of -6 carbon atoms, carbocyclic aryl groups of at least 6 carbon atoms, cycloalkyl groups of 3-12 carbon atoms, or 1-2 fused aromatic rings;
- and
- R' is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, trifluoromethyl, or C.sub.1 -C.sub.6 alkylsulfonyl.
A method of treating hypertension which comprises administering to a hypertensive person, in an amount effective to ameliorate the hypertensive state an N,N'-disubstituted amidine having the formula:
- ##STR12## wherein R and R" are a cycloalkyl group of at least 5 carbon atoms, a carbocyclic aryl group of at least 6 carbon atoms, alkaryl or aralkyl of at least 6 carbon atoms and containing 1-3 separate or fused rings, or a heterocyclic ring, wherein each of R and R" may be substituted in 1-3 positions, or wherein R and R" together with the amidine group may form a saturated or unsaturated cyclic ring containing at least 2 carbon atoms exclusive of the amidine carbon atom, wherein said cyclic ring may be substituted with one or more alkyl groups of 1-6 carbon atoms, carbocyclic aryl groups of at least 6 carbon atoms, cycloalkyl groups of 3-12 carbon atoms, or 1-2 fused aromatic rings;
- and
- R' is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, trifluoromethyl, or C.sub.1 -C.sub.6 alkylsulfonyl.
A method of treating hypertension which comprises administering to a hypertensive person, in an amount effective to ameliorate the hypertensive state an N,N'-disubstituted amidine having the formula:
- ##STR13## wherein X and Y are independently a branched or straight chain C.sub.1 -C.sub.8 alkylene or a branched or straight chain C.sub.2 -C.sub.8 unsaturated alkylene;
- R and R" are independently a cycloalkyl group of at least 5 carbon atoms, a carbocyclic aryl group of at least 6 carbon atoms, aralkyl of at least 6 carbon atoms and containing 1-3 separate or fused rings, or a heterocyclic ring, wherein each of R and R" may be substituted in 1-3 positions, or wherein R and R" may form a bond to give a saturated or unsaturated cyclic ring containing at least 2 carbon atoms exclusive of the amidine carbon atom, wherein said cyclic ring may be substituted with one or more alkyl groups of -6 carbon atoms, carbocyclic aryl groups of at least 6 carbon atoms, cycloalkyl groups of 3-12 carbon atoms, or 1-2 fused aromatic rings;
- and
- R' is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, trifluoromethyl, or C.sub.1 -C.sub.6 alkylsulfonyl.
Dependencies are inferred from the claim text.