US 5,204,353 AGranted

3-benzyl-3H-1,2,3-triazolo[4,5-d]pyrimidines, compositions thereof, and method of treating epilepsy therewith

AssigneeCiba-Geigy Corporation

InventorRene Meier

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Abstract

Tbe invention relates to 3H-1,2,3-triazolo[4,5-d]pyrimidine derivatives, especially substituted 3-benzyl-3H-1,2,3-triazolo[4,5-d]-pyrimidines of the general formula ##STR1## in which Ph represents a phenyl radical substituted by halogen, lower alkyl, trifluoromethyl and/or by cyano, R.sub.1 represents a free amino group or an amino group that is substituted aliphatically, cycloaliphatically, cycloaliphatically-aliphatically and/or by acyl, and R.sub.2 represents hydrogen, lower alkyl, a free amino group, or an amino group that is substituted aliphatically, cycloaliphaically, cycloaliphatically-aliphatically and/or by acyl, in free form or in form of a salt, with the proviso, that in a compound of formula I in free form, wherein R.sub.1 represents N,N-di-C.sub.1 -C.sub.6 -alkylamino in which the two N-C.sub.1 -C.sub.6 -alkyl groups may be the same or different, N-mono-C.sub.1 -C.sub.6 -alkylamino or amino, R.sub.2 is other than hydrogen and other than C.sub.1 - C.sub.6 -alkyl, if Ph represents a phenyl radical which is monosubstituted by halogen or by trifluoromethyl, and to compounds of formula I in free form wherein either Ph is o-fluorophenyl, R.sub.1 is N-mono-methylamino or amino, and R.sub.2 is hydrogen or methyl or wherein Ph is o-fluorophenyl, o-chlorophenyl or m-trifluoromethylphenyl, R.sub.1 is N,N-di-methylamino, and R.sub.2 is hydrogen or wherein Ph is m-fluorophenyl, p-fluorophenyl, o-chlorophenyl, o-trifluoromehylphenyl, m-trifluoromethylphenyl or p-trifluoromethylphenyl, R.sub.1 is N-mono-methylamino, and R.sub.2 is hydrogen. These compounds and salts can be used as pharmaceutical active ingredients and can be produced in a manner known per se.

Claims2

Dependent claims

A pharmaceutical preparation containing an internally administrable, antiepileptically effective amount of a compound of formula ##STR19## selected from the group existing of:

(a) in which Ph represents a phenyl radical that is substituted by at least one of halogen, lower alkyl, trifluoromethyl and cyano;
R.sub.1 represents amino, N-mono- or N,N-di-lower alkylamino, N-(lower alkoxy-lower alkyl)amino, N-(hydroxy-lower alkyl)amino, N-(hydroxy-lower alkyl)-N-lower alkylamino, N-mono- or N,N-di-cycloalkylamino, N-cycloalkyl-N-lower alkylamino, N-mono- or N,N-di-(cycloalkyl-lower alkyl)amino, N-(cycloalkyl-lower alkyl)-N-lower alkylamino, N-lower alkanoylamino, N-lower alkanoyl-N-lower alkylamino;
and
R.sub.2 represents amino, N-mono- or N,N-di-lower alkylamino, N-(lower alkoxy-lower alkyl)amino, N-(hydroxy-lower alkyl)amino, N-(hydroxy-lower alkyl)-N-lower alkylamino, N-mono- or N,N-di-cycloalkylamino, N-cycloalkyl-N-lower alkylamino, N-mono- or N,N-di-(cycloalkyl-lower alkyl)amino, N-(cycloalkyl-lower alkyl)-N-lower alkylamino, N-lower alkanoylamino or N-lower alkanoyl-N-lower alkylamino;
(b) in which Ph represents a phenyl radical that is substituted by at least one of halogen, lower alkyl, trifluoromethyl and cyano;
R.sub.1 represents amino, N-mono- or N,N-di-lower alkylamino, N-(lower alkoxy-lower alkyl)amino, N-(hydroxy-lower alkyl)amino, N-(hydroxy-lower alkyl)-N-lower alkylamino, N-mono- or N,N-di-cycloalkylamino, N-cycloalkyl-N-lower alkylamino, N-mono- or N,N-di-(cycloalkyl-lower alkyl)amino, N-(cycloalkyl-lower alkyl)-N-lower alkylamino, N-lower alkanoylamino, N-lower alkanoyl-N-lower alkylamino;
and
R.sub.2 represents hydrogen or lower alkyl;
in free form or in form of a pharmaceutically acceptable salt;
with the proviso that, in a compound of formula I in free form, wherein R.sub.1 represents N,N-di-C.sub.1 -C.sub.6 -alkylamino in which the two N-C.sub.1 -C.sub.6 -alkyl groups may be the same or different, N-mono-C.sub.1 -C.sub.6 -alkyl-amino or amino, R.sub.2 is other than hydrogen and other than C.sub.1 -C.sub.6 -alkyl, if Ph represents a phenyl radical which is monosubstituted by halogen or by trifluoromethyl;
(c) a compound of formula I in free form, wherein Ph is o-fluorophenyl;
R.sub.1 is N-mono-methylamino or amino;
and R.sub.2 is hydrogen or methyl;
(d) a compound of formula I in free from, wherein Ph is o-fluorophenyl, o-chlorophenyl or m-trifluoromethylphenyl;
R.sub.1 is N,N-di-methylamino;
and R.sub.2 is hydrogen;
and
(e) a compound of formula I in free form, wherein Ph is m-fluorophenyl, p-fluorophenyl, o-chlorophenyl, o-tri-fluoromethylphenyl, m-trifluoromethylphenyl or p-trifluoromehtylphenyl;
R.sub.1 is N-mono-methylamino;
and R.sub.2 is hydrogen;
or a pharmaceutically acceptable salt thereof and optionally at least one pharmaceutically acceptable adjunct.

18 more elements

A method for the treatment of epilepsy, characterized in that an antiepileptically effective amount of a compound of formula ##STR20## selected from the group existing of:

(a) in which Ph represents a phenyl radical that is substituted by at least one of halogen, lower alkyl, trifluoromethyl and cyano;
R.sub.1 represents amino, N-mono- or N,N-di-lower alkylamino, N-(lower alkoxy-lower alkyl)amino, N-(hydroxy-lower alkyl)amino, N-(hydroxy-lower alkyl)-N-lower alkylamino, N-mono- or N,N-di-cycloalkylamino, N-cycloalkyl-N-lower alkylamino, N-mono- or N,N-di-(cycloalkyl-lower alkyl)amino, N-(cycloalkyl-lower alkyl)-N-lower alkylamino, N-lower alkanoylamino, N-lower alkanoyl-N-lower alkylamino;
and
R.sub.2 represents amino, N-mono- or N,N-di-lower alkylamino, N-(lower alkoxy-lower alkyl)amino, N-(hydroxy-lower alkyl)amino, N-(hydroxy-lower alkyl)-N-lower alkylamino, N-mono- or N,N-di-cycloalkylamino, N-cycloalkyl-N-lower alkylamino, N-mono- or N,N-di-(cycloalkyl-lower alkyl)amino, N-(cycloalkyl-lower alkyl)-N-lower alkylamino, N-lower alkanoylamino or N-lower alkanoyl-N-lower alkylamino, in free form or in form of a pharmaceutically acceptable salt;
(b) in which Ph represents a phenyl radical that is substituted by at least one of halogen, lower alkyl, trifluoromethyl and cyano;
R.sub.1 represents amino, N-mono- or N,N-di-lower alkylamino, N-(lower alkoxy-lower alkyl)amino, N-(hydroxy-lower alkyl)amino, N-(hydroxy-lower alkyl)-N-lower alkylamino, N-mono- or N,N-di-cycloalkylamino, N-cycloalkyl-N-lower alkylamino, N-mono- or N,N-di-(cycloalkyl-lower alkyl)amino, N-(cycloalkyl-lower alkyl)-N-lower alkylamino, N-lower alkanoylamino, N-lower alkanoyl-N-lower alkylamino;
and
R.sub.2 represents hydrogen or lower alkyl;
in free form or in form of a pharmaceutically acceptable salt;
with the proviso that, in a compound of formula I in free form, wherein R.sub.1 represents N,N-di-C.sub.1 -C.sub.6 -alkylamino in which the two N-C.sub.1 -C.sub.6 -alkyl groups may be the same or different, N-mono-C.sub.1 -C.sub.6 -alkyl-amino or amino, R.sub.2 is other than hydrogen and other than C.sub.1 -C.sub.6 -alkyl, if Ph represents a phenyl radical which is monosubstituted by halogen or by trifluoromethyl;
(c) a compound of formula I in free form, wherein Ph is o-fluorophenyl;
R.sub.1 is N-mono-methylamino or amino;
and R.sub.2 is hydrogen or methyl;
(d) a compound of formula I in free form, wherein Ph is o-fluorophenyl, o-chlorophenyl or m-trifluoromethylphenyl;
R.sub.1 is N,N-di-methylamino;
and R.sub.2 is hydrogen;
and
(e) a compound of formula I in free form, wherein Ph is m-fluorophenyl, p-fluorophenyl, o-chlorophenyl, o-tri-fluoromethylphenyl, m-trifluoromethylphenyl or p-trifluoromethylphenyl;
R.sub.1 is N-mono-methylamino;
and R.sub.2 is hydrogen;
or a pharmaceutically acceptable salt thereof is administered to a subject in need of such treatment.

18 more elements

Dependencies are inferred from the claim text.